American with Disabilities Act (ADA) & Section 504 Overview & Reasonable Accommodations

by Janet Brewer, M.Ed & Lisa Cosseboom, M.Ed., CAGS

Published: Lifelines for Health Fall 2019

Section 504 of the Rehabilitation Act of 1973: The 504 section of this law was enacted to provide people with disabilities protection against discrimination by any program, activities or schools (as well as colleges and universities) that receive federal funding. The Office of Civil Rights (OCR) are responsible for enforcing institutions to provide reasonable accommodations for “qualified individuals.”

American with Disabilities Act (1990): This amendment in 1990 widened the breadth of coverage for people with disabilities. The act notes that its purpose is “to provide a clear and comprehensive national mandate for the elimination of discrimination against individuals with disabilities.” Part of this act prohibits a “public entity” such as a public school and non-parochial private schools from discriminating against students with a disability.

What is considered discriminatory?

• Denying a qualified student with a disability the opportunity to participate in or benefit from the aids, benefits, or services that are afforded other students.

• Affording a qualified student with a disability an opportunity to participate in or benefit from the aids, benefits, or services that are not equal to that afforded other students.

• Providing aids, benefits, or services to a qualified student with a disability that are not as effective as those provided other students.

• Providing different or separate aids, benefits, or services to a qualified student with a disability unless necessary to provide aids, benefits, or services that are as effective as those provided others.

• Aiding or perpetuating discrimination by providing significant assistance to an agency, organization, or person that discriminates on the basis of a disability.

• Denying qualified persons with disabilities the opportunity to participate as a member of a planning or advisory board because of their disability.

• Limiting a qualified student with a disability from the enjoyment of any right, privilege, advantage, or opportunity enjoyed by other students.

How is a disability determined?

The law states that a person must:

• Have a physical or mental impairment which substantially limits one or more major life activities (those basic activities that the average person in the general population can perform with little or no difficulty)

• Has a record of such impairment

• Is regarded as having such an impairment

The term “substantially limits” one major life activity can be episodic or in remission and still be considered a disability and have accommodations in place for when it is active; and the determination must be made without regard to the ameliorative effects of mitigating measures.

What does this mean?

The 504 Team must identify mitigating measures being used by a student and determine how the disability would impact the major life activity in the absence of the mitigating measure. For example, a student with an inhibitor who happens to not be actively bleeding, or is currently managing any bleeding disorder with infusions (any type of medication is a mitigating factor), the

Team must determine whether the impairment would substantially limit a major life activity if removed. Each mitigating measure must be identified and used to determine what the impairment would look like if the mitigating measure was removed. Additionally, the Office of Civil Rights has determined that health plans and emergency plans are considered mitigating measures.

Examples of mitigating measures:

• Medication, medical supplies, equipment, or appliances; low-vision devices (which do not include ordinary eyeglasses or contact lenses); prosthetics, including limbs and devices; hearing aids and cochlear implants or other implantable hearing devices; oxygen therapy equipment and supplies; use of assistive technology;

• Reasonable accommodations or auxiliary aids or services; and

• Learned behavioral or adaptive neurological modifications.

The purpose of a 504 plan is to provide access or remove barriers to participation. It provides students the same rights and services as their non-disabled peers. For students with bleeding disorders, a major life activity could include walking, writing, sitting or standing. Under a 504 plan a student can access related services as determined by the Team. These include the following:

Speech & Language Therapy:

• Occupational Therapy

• Physical Therapy

• Counseling

• Rehabilitative Counseling

• School health services

• Transportation

Reasonable Accommodations under a 504 plan:

• Schedule of Physical Education activities

• Extra set of books at home

• Extended travel time around building

• Extended time for homework/make-up work

• All medically related absences are excused with no loss of credit

• Field trips to include a nurse

• Permanent pass to the school nurse

• Medications, needles and supplies maintained in the nurse’s office

• Staff in-service

• Tutoring due to absences

• Physical education credits for participating in outside physical therapy

• Audio or video of class lectures

• Regular email contact from teachers regarding missed assignments

• Note takers/Copies of teacher notes

• Homework posted on the school district internet (Class Dojo/Google Classroom)

• Permanent pass for school elevator

• Walkie-Talkies for recess

• Medically-related absences excused with no loss of credit

• Individualized Health Care Plan

What about after-school programming?

• Medications, needles and supplies maintained in the nurse’s office

• Staff in-service

• Tutoring due to absences

• Physical education credits for participating in outside physical therapy

• Audio or video of class lectures

• Regular email contact from teachers regarding missed assignments

• Note takers/Copies of teacher notes

• Homework posted on the school district internet (Class Dojo/Google Classroom)

• Permanent pass for school elevator

• Walkie-Talkies for recess

• Medically-related absences excused with no loss of credit

• Individualized Health Care Plan

Any program that is operated or funded by a school or contracted by a school is required for ensuring reasonable accommodations for children on a 504 or Individualized Health Plan. The school district, family and after-school program should work to ensure consistency between the school plan and what accommodations the student needs in the after- school setting.

Parents should plan on advocating for their child in the school system as bleeding disorders are rare and school staff may be unfamiliar with their needs or what accommodations will be needed. After reasonable requests for 504 eligibility, if a family has a complaint contact the Office for Civil Rights at:

https://www2.ed.gov/about/offices/list/ocr/qa-complaints.html

A Journey of Faith

Published: Lifelines for Health Spring 2019

In November 2018, I had the opportunity to attend the ‘Mom’s Uninhibited Meeting (MUM) offered by CHES. It was by chance that I saw the social media post and figured I wouldn’t be able to attend with everything going on in my life, but thankfully, I did! I had no idea what to expect. My weekend started as I boarded the plane to Nashville. It was difficult being away from my family for the first time since my son had been born. Although, after the evening session that day, I immediately felt that I had made the right decision. The first night was special because it set the stage for the rest of the weekend. Even though I had never met any of these lovely women, it was easy to talk with them and share experiences since we all knew we had at least one thing in common. That night, I felt emotionally drained because the words that were shared struck a chord with me. The weight of my feelings was put into words that I could not or dared not articulate, or even think about, but benefited deeply from hearing them spoken.

My son was diagnosed with severe Hemophilia A in the early summer of 2018. About a month after that diagnosis, we found out he had developed inhibitors. To say we were overwhelmed is an understatement. The information that we had to take in seemed impossible to digest. Right when we thought we had a handle on it, something new would come up. Having the opportunity to learn and take things in that weekend opened my eyes to how much I still need to learn but also, more importantly, that my family has a choice when it comes to my son’s treatment and we can and should ask questions.

The educational sessions provided were eye opening. Since every mom had a different story and had been on their journey for different amounts of time, it was even more helpful. Each had different questions and stories that sparked questions for me and helped me learn even more than what was taught during the sessions. These things all changed my perspective on my son’s treatment. It has enabled me
to have a stronger voice when speaking with his doctors and it encouraged me to continue to champion for his best interest. Thanks to the help of Kathy Byrne, I was even able to stick my own vein! Having never been a fan of needles, it really was a milestone for me, and it encouraged me that someday I can learn to do the same for my son.

I think that every mom with a child who has an inhibitor should attend the MUM program. For the moms that are just beginning on this journey like I was, it was a great opportunity to learn, connect, and share. For moms that are further along in their journey, it was a great opportunity to guide and support those of us who are just getting started. I can’t thank Janet, and the CHES team enough for offering such a wonderful weekend. I am very grateful for the opportunity that I had to experience this MUM weekend.

Amy and her husband, Oscar have been married for 4 years and live in Orange County, CA with their 2-year-old son Hudson. She works at the Disneyland Resort as a Food and Beverage manager.

Momentum, Men's Inhibitor Retreat: Brotherhood

Published: Lifelines for Health Spring 2019

Between managing my own health (including a daily ITT regimen), partially running a business, raising two small children who have recently been dually-diagnosed with bleeding disorders, cheer practice, dance practice, and being married to a spouse who also works, “overwhelmed” has become a word of persistency in my life.

Momentum (CHES’ men’s inhibitor retreat) was created to improve the quality of life for adults living with active inhibitors. As one of the creators of Momentum, I can humbly say that I benefit just as much as the average Joe. Or in this case, the average Bro. That’s what these meetings become to most of us. It’s not just a place of resources to better our lives, it’s also a brotherhood.

As Janet and I were prepping for Momentum last summer (along with the rest of the CHES team), she asked me if I was ready for this. “This” meaning acting as the lead facilitator of the program, as she (who usually takes on this responsibility for most CHES programs) would not be attending. After 10 years of doing this, I still feel the nerves of most people’s biggest fear - public speaking. But to Janet’s question, I replied, “absolutely, these are my people.” When I speak to this group, I’m not hosting guests or friends. I’m strengthening the bonds of my brothers as well as my own.

Some of these guys I’ve known for years, and some were new acquaintances for me, but we all have opened arms to each other. There are no judgements, no cliches’, no negativity, hatred, or disrespect - only brotherly love and acceptance. We feel we understand each other better than anyone else can. And although we may not see or speak with each other more than a few times a year, the connection picks right back up where it left off.

Serving my overwhelmed state was the opener to the weekend, which was both happily welcomed and received as Emily Taylor sat us all down in a circle for some mindfulness techniques and theory of pain exercises.

Although I don’t recall the specific methods of the session, I do remember leaving in a calm, relaxed state.

As someone who has just surpassed their 11th anniversary of ITT, vein preservation is a big concern. Like almost everyone else in this group, I can jokingly say I could be a phlebotomist tomorrow if I wanted to. But CHES’ acclaimed Kathy Byrne, who has decades of infusion experience under her belt, had tips that even I had not known of. Just changing to a 27 gauge needle has really proven to provide more mileage out of my veins. And marking a hard-to- find vein with a fingernail impression has bumped my “sticking average” up to nearly 100%. But I’m not going to reveal all of her secrets here, as I hope to see each and every (qualifying) person who reads this article at a CHES program.

Dr. Jonathan Bernstein of Connecticut Children’s Medical Center in Hartford gave us the updates on the latest and greatest products for inhibitor folks, as well as some that we either overlooked or had forgotten. After all, some products may not be new and shiny, but that doesn’t mean doctors and researchers aren’t reinventing treatment methods around them. Personally, the variety of products and the multitude of concerns and unanswered questions surrounding them are yet another overwhelming factor in my life, so I have chosen the wait-and-see method while maintaining ITT.

To close the programs off, we hopped in the pool as Chad Brown, ex pro-am wake boarder with hemophilia A and professional coach as president/CEO of the Wingmen Foundation, gave us some lessons on low-impact, water aerobics in a playful yet beneficial manner.

I look forward to reconnecting with all of our community friends and family each year at our programs, but Momentum is really something extra special to me. As I said, “my people”.

SAFE ACCESS to CANNABIS A Desire for the Masses, Necessity for Some

By: Mark Zatyrka

Published: Lifelines for Health Spring 2019

It is reported that over 100 million US adults deal with chronic pain. Statistically 1 out of every two patients report pain as being the cause for inquiry with a medical professional (Zou & Kumar, 2018). With the cost of the prescribed pain medications being above a half a trillion dollars annually, many go into medical bankruptcy trying to find a reasonable quality of life. Most are willing to embrace a naturally occurring compound because it can be digested by the body and mind without severe negative side effects, contrary to over the counter drugs and prescriptions which come with an array of side effects and often result in patients needing to take additional medication (sometimes 3-4) to alleviate side effects caused by the first medication. The stream of medications at times can seem endless for those in chronic pain management situations and those with debilitating health issues.

The medical community has discovered that several components of the cannabis plant offer daily relief from pain, nausea, sleep issues, seizures, depression and anxiety. The component that is most widely recognized and utilized currently is known as Cannabidiol, or more commonly “CBD”. CBD is the crucial component within certain cannabis strains, aiding in the relief from a plethora of potential health issues. It is the non-psychoactive compound that offers a wide array of medicinal benefits without resulting in the feeling which is commonly referred to as being ‘high’. This feeling of being high is a result of the other well-known component of cannabis, THC (Kubala, 2018).

Endocannabinoid System

Similar to hemophilia, the endocannabinoid system is rarely discussed in medical schools, however, we are learning it can play an important role in our overall health. Each person is born with an endocannabinoid system which helps regulate different physiological and cognitive processes from fertility to the sensations of pain. This internal processing system in each one of us is the primary reason we as humans can utilize cannabis for a wide range of effects that it can present when used in various ways. Our endocannabinoid system is essentially the system which allows for and develops communication between our cells. The CB1R and the endocannabinoid system are largely involved in various aspects of central neural activities and disorders, including appetite, learning and memory, anxiety, depression, schizophrenia, stroke, multiple sclerosis, neurodegeneration, epilepsy, and addiction (Zou & Kumar, 2018).

Your body can naturally receive and process all parts of the cannabis plant without harm or side effects to your body when it is used properly and efficiently. Cannabinoids resemble endocannabinoids and can essentially be absorbed and recognized by your body as though they were internally produced. Cannabinoids bind to receptor sites in your brain and body that allow for the different effects, which are varying by the cannabis strain, to take place. Within your body, what are known as your CB1 and CB2 receptors are largely involved in various aspects of central neural activities and disorders, including appetite, learning and memory, anxiety, depression, multiple sclerosis, neurodegeneration, epilepsy, and even addiction (Mary’s Medicinal’s, 2018).

Previously, cannabis wouldn’t even enter the conversation until young adulthood, but now more than ever parents are looking to cannabis to solve the severe issues that their child may be dealing with. We are on the precipice of understanding the benefits of cannabis with children, therefore long-term scientific data is not available at this point, yet there are many anecdotal and surface studies that have occurred to open the minds of many.

Family Focus

A renowned case of success in the use of cannabis with children is that of Charlotte Figi and her family. Charlotte was age 2 when she had her first seizure. Her family physicians were absolutely convinced it was a onetime occurrence, but this became a prevalent issue in all of their lives. Ultimately, she was diagnosed with
a rare form of epilepsy called Dravet Syndrome. This is a type of epilepsy that typically does not respond to normal forms of medication or therapy. Her family felt helpless as their baby seemed to be slipping away and they worried about her ongoing development. As they went down every road that western medicine had to offer, they eventually had to accept that it was time to consider an alternative. This is when Charlotte’s family began the conversation with their physician about the use of CBD oil. They had heard anecdotal reports of cannabis helping with the frequency of Grand Mal seizures in adults and were curious if their daughter could benefit from such a regimen as well.

Although no doctor wanted to risk their license on approving the use of CBD oil for Charlotte due to her age, the family did not give up. Eventually they found Dr. Margaret Gedde, who approved the use of ‘pure CBD oil’ for her seizures. The next step was a long process, but they were able to find the Stanley brothers who had been growing medical marijuana for quite some time and were already heavily focused on isolating the genetics that were best suited for cultivating one specific component, CBD. They were able to go through and identify the specific traits within the strain, that they would eventually name Charlotte’s Web, to ensure less than 0.3% THC would be present within each yield along with very high levels of CBD. The Stanley brothers’ pride in themselves on providing access to safe cannabis is their life long goal, which they are achieving daily. From the cannabis grown by the Stanley brothers they were able to create a high end and very potent CBD focused oil extracted from the plant itself. Charlotte went from dealing with 300+ Grand Mal seizures per week to less than 1 per week with the use of the CBD oil produced for her. This case is the cornerstone of how the cannabis industry and CBD industry took the momentum they had gained via countless decades of initiatives and used it to launch the next phase in the cannabis movement (tiffany@ sweethoneybeehealth.com, 2018).

What the Figi family was able to achieve, by finding a responsible vendor and a medical professional who was willing to provide access to high- end medicinal cannabis, may easily be identified as a historical turning point for the cannabis industry. As a result of coverage of Charlotte’s story by numerous media outlets including CNN, acceptance and excitement around the potential surrounding CBD rose overnight; over the past 5-6 years, families have become increasingly willing to move across the country in order to gain legal and safe access to this plant- based medication. Hundreds of families have made this journey, uprooting their family from their home state in order to pursue accessible legalized marijuana, forgoing any federal laws in the pursuit of this medical alternative.

Colorado has become the ‘end all, be all’ for parents in pursuit of medicinal marijuana as a treatment for their children. “Hundreds of families have moved to Colorado in hopes of healing their sick children — kids conventional medicine has failed” (Ingold, Amon, & Pierce, 2014). While some are met with helping hands and success stories erupt, others are met with a harsher reality that they are too late for CBD to help, or they lack accessibility to help in administering cannabis treatments and creating proper regimens for proper dosing, so they are left to their own devices and must administer the medication to their children in their own home without proper guidance.

Overall, the amount of research and information regarding children and medicinal use of cannabis is quite minimal, therefore we must rely on current research to continue to decipher the reality of cannabis within the medical community. This has done little to hinder the hundreds of registered medical marijuana patients under the age of 18, brought by their parents to Colorado: In 2014 there were 400+ registered patients under the age of 18, many of whom were not residents of the state until after seeing the CNN report on Charlotte Figi and her progress (https://www. colorado.gov/, 2017).

Mark and Maria Botker from Minnesota were willing to separate their own family to find help for Greta, their 7-year-old child. While Maria traveled to Colorado with Greta seeking medical help, Mark remained behind at their farmhouse in Minnesota with their two older daughters (10, 13). In search of any help in mitigating the number of seizures their daughter was incurring daily, the family had gone through multiple rounds of pharmaceutical regiments and went as far as allowing brain surgery to be performed on Greta, but nothing helped. They came to a final resolution that their next step was to investigate cannabis and the potential for CBD (Bello, 2014). After only a few months of living in Colorado they realized their neighbors, Anna and Biagio Burriesci, were dealing with a very similar situation. The Burriesci family moved to Colorado from New York seeking the benefits of medical marijuana for their young daughter Grace. In doing so, they lost their jobs and their financial security, taking over a $200,000 loss on their estate in Queens, New York in order to pursue accessible and legalized medical cannabis. “This condition ultimately meant death for our kid, so we were going to war for her,” “Families are desperate,” Biagio stated. Their daughter went from experiencing 300 seizures a day to less than 5 daily and, thanks to the reduction in her episodes, she was able to learn useful motor skills to aid in coping through these episodes (Bello, 2014).

Breakthrough within the Cannabis Community

In June of 2018 the FDA approved the use of concentrated CBD, called Epidiolex, to treat rare forms of epilepsy. This non-synthetic cannabis-derived product is the first plant- derived cannabinoid pharmaceutical ever approved by the FDA. The company that created it, known as Greenwich Biosciences, has been at the helm of outstanding research, creating an avenue for specific cannabis products to become mainstream. Epidiolex has been available since November 2018, with sales in the first 2 months rising over a staggering $4.5 million dollars, and over 500 physicians prescribing this medication, the demand and support for this medication is apparent.

As we continue to advance with research and development, we are also gaining approval by the government, setting the stage for the future of other cannabis products and overall legalization (Partnership, 2018). Only 3 months after the release of Epidiolex, the U.S. Drug Enforcement Administration removed certain forms of CBD products from the Schedule 1 class and reclassified the cannabis-derived products as Schedule 5. This decision is the first official admission by the government that cannabis has medicinal value. Anything that is on the approved list of items and tests under 0.1% of THC is federally approved for sale and use with a prescription. CBD products derived from cannabis will be available for the masses in our lifetime, guaranteed, but it is not over yet as we all need to help and continue to move the needle in the right direction for overall progression (Hemp Industry Daily, 2018).

On March 12, 2019 a legislative bill, initiated by a Wichita couple with special needs children, will be moving forward in Topeka. “House Bill 2244 was introduced into the Kansas legislature to allow people with life-threatening medical conditions to get treatment with CBD oil with a small amount of THC.” In its title, the bill “authorizes the use of cannabidiol treatment preparation to treat certain medical conditions.” Both daughters of Gwen and Scott Hartley were born with microcephaly, a birth defect that causes the head to be under-developed and therefore smaller. Claire recently passed at the age of 17, and her parents have dedicated their lives to helping their 12-year-old live a full life. Titled “Claire and Lola’s law”, their parents hope to help other families seeking advice on, help with, and most importantly access to, CBD oil. The reality of this law change could be ground breaking, as Claire and Lola’s mother Gwen explained: The law is actually an affirmative defense law which would allow us to go to a legal state, purchase the THC CBD oil that would benefit our child, bring it back into Kansas and not get arrested or lose custody of my child,” Gwen explained last week. If this was approved this could be the light at the end of the tunnel for numerous families and a signal to other states to lift the ban on CBD use for severely debilitating disorders and life-threatening illness (Viviani & Kwch, 2019).

Many adults wonder: Is cannabis safe? Why would cannabis be the best option? Will it help? If I were to choose this route will my personality or decision-making change, or be altered in some way? Is it safe enough for my child? Is it proven to help my/my child’s disorder or level of pain? These are all valid questions when first entering the world of cannabis. I am always excited to share with others that it is proven through scientific studies over decades of research, that our own individual endocannabinoid system is intended to receive and utilize all types of cannabinoids.

With legalization and decriminalization on the rise, we are finally moving the needle in the right direction for cannabis patients and users across the United States. 33 states have approved medical access for patients and 10 states have approved recreational access for patrons. The level of progress at the state level gives momentum and hope for legalization at the federal level, making this an approved substance across the country and allowing for safe access for the masses (NCSL, 2018).

It can bring a grown man to his knees to see his only child in danger or worse to see them facing death at a young age. Those that are dealing with the consistent thought and therefore mindset of losing a child to a type of disorder or disease that can be treated in the same country that you are a citizen within seems unjustifiable. Many of us seek a quality of life balance as we get older and realize what is important to us. What if you were never given the chance to feel love, to speak to your parents, to feed yourself your favorite meal or play a board game during a family gathering? Many of us in the bleeding disorders community know how it feels as a parent of a child that could not enjoy their young life. Please ask yourself some hard questions and try to put yourself in another’s shoes to try and feel the level of utter dismay and confusion that they feel day in and day out. The way we resolve this issue is to keep this subject on the forefront of discussions until all laws are altered or changed in a way to allow for safe and responsible access to cannabis and all products derived from this plant. It can change the world if given the chance.

References:

Bello, M. (2014, February 18). Parents move to Colorado for ‘miracle’ pot for children. Retrieved March 8, 2019, fromhttps://www.usatoday.com/story/news/nation/2014/02/17/ moving-medical-marijuana-epilepsy-children/5255323/

G. (2019). MS Spasticity. Retrieved March 8, 2019, from

https://www.gwpharm.com/healthcare-professionals/ sativex/patient-information

Hemp Industry Daily. (2018, September 27). DEA moves CBD medicines off Schedule 1, reclassifying as Schedule 5. Retrieved March 8, 2019, from https://mjbizdaily.com/dea- moves-cbd-medicines-off-schedule-1-a-limited-expansion- of-cannabis-access/

Hill, K. P., Palastro, M. D., Johnson, B., & Ditre, J. W. (2017). Cannabis and Pain: A Clinical Review. Cannabis and Cannabinoid Research, 2(1), 96-104. doi:10.1089/ can.2017.0017

Ingold, J., Amon, J., & Pierce, L. (2014). CBD in Colorado: Seeking a marijuana miracle. Retrieved March 8, 2019, fromhttp://extras.denverpost.com/stateofhope/

Kubala, J. (2018, February 26). 7 Benefits and Uses of CBD Oil (Plus Side Effects). Retrieved March 1, 2019, from https:// www.healthline.com/nutrition/cbd-oil-benefits

Colorado.gov. (2017, August). Medical Marijuana Registry Program Statistics [PDF]. State of Colorado.

G. (2019, February 26). GW Pharmaceuticals plc Reports Financial Results and Operational Progress for the Quarter Ended December 31, 2018. Retrieved March 8, 2019, from http://ir.gwpharm.com/news-releases/news-release-details/ gw-pharmaceuticals-plc-reports-financial-results-and- operational

Mary’s Medicinals. (Ed.). (2018). SCIENCE OF CANNABINOIDS. Retrieved March 1, 2019, from https:// marysmedicinals.com/science/

NCSL. (Ed.). (2018, December 14). MARIJUANA OVERVIEW. Retrieved March 03, 2019, from http://www.ncsl.org/ research/civil-and-criminal-justice/marijuana-overview.aspx

Partnership. (2018, October 03). What Parents Should Know About Kids Using CBD. Retrieved March 8, 2019, from https://drugfree.org/parent-blog/what-parents-should- know-about-kids-using-cbd/

Sam. (2019). Home. Retrieved March 8, 2019, from https:// www.theroc.us/

Tiffany@sweethoneybeehealth.com. (2018, August 3). CBD, Charlotte Figi and Fighting for Life. Retrieved March 8, 2019, from http://sweethoneybeehealth.com/cbd/2018/08/03/ cbd-charlotte-figi-and-fighting-for-life/

Viviani, N., & Kwch. (2019, February 28). Bill allowing THC CBD oil for medical treatment moves forward in Topeka. Retrieved March 8, 2019, from https://www.wibw.com/ content/news/Bill-allowing-THC-CBD-oil-for-medical- treatment-moves-forward-in-Topeka-506519011.html

Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, 19(3), 833. doi:10.3390/ijms19030833

MASAC Recommendations: HEMLIBRA

Published: Lifelines for Health Spring 2019

The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) released their recommendations on the use of Hemlibra (emicizumab) on December 6, 2018. Hemlibra was approved for use on November 16, 2017 for persons with hemophilia A and inhibitors. In addition, it was approved for persons with hemophilia A with or without an inhibitor on October 4, 2018. For purposes of this article, CHES’ focus remains on the inhibitor community.

For full MASAC recommendations: https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC- Recommendations/Recommendation-on-the-Use-and-Management-of-Emicizumab-kxwh-Hemlibra-for-Hemophilia-A- with-and-without-Inhibitors

Clinical Management Guidance

*Full prescribing information is available in the package insert. In addition, the prescribing information contains
a boxed warning regarding the risk of thrombotic microangiopathy (TMA) and thromboembolism. Because of the complexity of these adverse events in association with the use of activated prothrombin complex concentrates (aPCC) to treat breakthrough bleeding in patients receiving emicizumab, it should be prescribed and bleeding events should be followed by, or in close coordination,

with all the appropriate staff of the patient’s HTC, including physicians/providers and nurse coordinators. The following recommendations are intended to address clinical management issues that are not addressed fully within the package insert.

1. Who is appropriate to be considered for treatment with emicizumab?

Physicians caring for persons with hemophilia A (PwHA), of any age or severity, with or without inhibitors should discuss this new therapeutic option with them, including an assessment of the risks and benefits of emicizumab compared to their existing therapy. However, based on the clinical trial data, any PwHA with an inhibitor who is having frequent bleeding episodes and is on either episodic therapy or bypassing agent (BPA) prophylaxis will likely derive significant benefit from emicizumab. Those on BPA prophylaxis with few bleeding episodes could either continue on that BPA or could consider switching to emicizumab based on overall cost-effectiveness and reduced burden of administration. In addition, infants should be considered for prophylaxis with emicizumab at any time after birth given the increased risk of intracranial hemorrhage prior to initiation of FVIII prophylaxis. Note, there is limited data on the use of emicizumab in infants under 6 months of age and the pharmacokinetic exposure is likely to be lower compared to older infants and children. We strongly encourage prospective data collection concurrent with its use in this age group.

2. Recommendations for initiation of emicizumab

a. PwHA and inhibitors Administration of activated prothrombin complex concentrates (aPCCs) should be discontinued at least 24 hours prior to initiation of emicizumab.

b. PwHA and no inhibitors... (skipped)

c. Patient education should include:

i. Giving the loading dose(s) under medical supervision, in order to review and observe self-administration technique, and determination of what dose will be used after the 4-week loading period is complete.

ii. Discussion of the appropriate clotting factor product (factor VIII concentrate or bypassing agent) and dose
to use for a breakthrough bleed, review of the signs
and symptoms of a bleed, and stressing the need to contact the Hemophilia Treatment Center (HTC) if a breakthrough bleed requires more than 1-2 treatments and/or is not responsive to treatment. iii. Warning against concomitant use of aPCCs and associated risks, including what a thrombosis is, and the associated symptoms and to seek medical help should it occur

iv. Reminding when emicizumab is re-ordered, patients must provide their current weight to assure proper dosing and proper vial combinations to achieve the calculated dose.

v. Patients must contact the HTC in the event of surgery, whether elective or emergent, to assure a plan for treatment is developed, including if any clotting factor product will be used, and, if so, at what dose and frequency, and if antifibrinolytic agents are advised.

vi. Patients should be warned that if they stop emicizumab, residual plasma levels may persist for as long as 6 months, and thus, risk mitigation regarding the use of aPCCs should be used during that 6-month period to avoid the risk for thrombotic and TMA complications

vii. Regular clinical review of the efficacy for bleed prevention should be conducted once the patient has reached the maintenance dosing and at 3 months, 6 months and 12 months after initiation of therapy, and thereafter at 6 month intervals at the discretion of their physician.

viii. Loss of efficacy should prompt evaluation for anti- drug antibodies (see below).

ix. Patients should be counseled they should continue to travel with an emergency dose of factor concentrate to allow prompt management of any significant and serious or life-threatening bleeding

3. Recommendations on Acute Bleed Management – PwHA and Inhibitors

Despite the high efficacy in the prevention of bleeding events, clinicians and patients should still expect breakthrough bleeding events in patients on emicizumab prophylaxis, which in PwHA with inhibitors will likely mean the need for concomitant use of alternative hemostatic therapies. Due to the serious adverse events observed in the clinical trial program, we are reiterating below the previous interim guidance on management of breakthrough bleeding, surveillance for thromboembolic and TMA events, and recommendation on appropriate
use of laboratory assays. No TMA or serious thrombotic events have been reported to date with adherence to these management principles after implementation within the global clinical trial program or since commercial availability within the US in pediatric and adult patients.

a. General approach to breakthrough bleeding: Emicizumab is likely to transform the bleeding phenotype of patients to a milder phenotype.
Given improved baseline hemostasis in patients on emicizumab prophylaxis, the current paradigm of treating at the first signs and symptoms of bleeding
in some cases should change. Significant and serious or life-threatening bleeding should continue to be treated promptly. However, there should be additional evaluation of muscle and joint complaints prior to treatment with an additional hemostatic agent. For equivocal signs or symptoms of minor bleeds, the patient should contact their provider before initiating bypass therapy treatment.

b.

Caution with dose and duration of bypass therapy:

i. Acute bleeding events should be managed with rFVIIa, at a dose of 90-120 mcg/kg as an initial dose. The vast majority of bleeds should be able to be managed with 1-3 doses administered at no more frequency than q2h intervals.

ii. Use of aPCC for breakthrough bleed treatment
for patients on emicizumab should be avoided if possible, and rFVIIa should be the first option used to treat. If aPCC is used, it should be limited to no more than 50 IU/kg administered as an initial dose and
not exceed 100 IU/kg/day. Duration of aPCC therapy should also be minimized, as prolonged use for >24 hours, especially with doses above 100 IU/kg/day, was associated with thrombosis and TMA.

iii. Repeated dosing of any BPA beyond the above recommendations should be performed under medical supervision with consideration for verifying severity of bleeds prior to continuing to repeat dosing.

iv. For significant bleeding that is not responding
to BPA, consider using porcine factor VIII or human FVIII if partially tolerized. Use of these agents would also allow therapeutic monitoring with access to the bovine chromogenic assay.

v. Clinical and laboratory monitoring: All patients
on emicizumab who have received aPCC for breakthrough bleeding for more than 24 hrs should be evaluated for any clinical symptoms that could
be consistent with a thromboembolic event (with a high level of suspicion for atypical sites, e.g. cerebral sinus venous thrombosis), should have laboratory monitoring to look for evidence for TMA (this should include D-dimer, prothrombin fragment F1+2 (if available), platelet count, serum creatinine, LDH
and peripheral blood smear analysis to look for schistocytes). Monitoring should continue daily while the patient continues to receive aPCC until 48 hours following the last dose of aPCC.

vi. Management of TMA: Use of aPCC should cease immediately. The half-life of emicizumab is 28 days and it will remain in the patient’s system for months after discontinuation of emicizumab. Each of the reported cases of emicizumab+aPCC TMA resolved quickly after discontinuation of aPCC with supportive care alone or in conjunction with plasmapheresis. In the 2 cases treated with plasmapheresis, emicizumab was not completely removed and in spite of discontinuation of emicizumab one of these patients had measurable emicizumab laboratory effects for several months. Emicizumab was restarted in two patients without recurrence of TMA.

4. Recommendations on Acute Bleed Management – PwHA without inhibitors... (skipped)

5. Recommendations on laboratory assays while on emicizumab

Although emicizumab mimics the function of activated factor VIII, it is biologically different from activated factor VIII, having much lower affinity for factor IXa and X, not requiring activation, and not deactivated by the protein C/S pathway. These fundamental differences affect our interpretation of clotting assays.

a. Laboratory monitoring of emicizumab is not required while on routine prophylactic dosing

b. aPTT-based assays, including clot-based FVIII activity assays, should not be performed while on emicizumab, as they will yield misleading results (ie. artifactually shortened aPTT and elevated FVIII activity).

c. Chromogenic FVIII activity assays will only provide an assessment of emicizumab activity if the assay includes all human reagents but these are not widely available. A chromogenic FVIII assay that uses bovine reagents may be used to assay the FVIII activity of any additional FVIII concentrate administered or endogenous FVIII.

d. The clot-based Bethesda assay cannot be utilized to assess FVIII inhibitor levels. However, a bovine-reagent chromogenic-based inhibitor assay can report out FVIII inhibitor levels. If samples are submitted to the CDC for central laboratory testing, they must be clearly identified that the patient is on emicizumab.

e. Exploratory laboratory assays:

i. Thromboelastography/thrombelastometry/ thrombin generation

ii. Clot waveform analysis

These and other assays under continued investigation are likely to allow for quantitation of emicizumab concentration from plasma. However, due to the intrinsic differences between emicizumab and FVIII, this complicates assignment and interpretation of FVIII-equivalent activity. Caution should remain in extrapolating clinical correlates using ‘FVIII- equivalence’ from such assays until further clinical data is available.

1. Anti-drug antibodies:

a. The prescribing information for emicizumab includes important safety information on the risk for anti-drug antibodies. Use of any therapeutic protein carries the potential for the development of anti- drug antibodies. These were observed within the global clinical trial program with emicizumab and are described within the US and European Union (EU) emicizumab product labels. The immunogenicity of emicizumab was evaluated using an enzyme-linked

immunosorbent assay or an electrochemiluminescence assay. In the dose-finding trial (n = 18), four patients tested positive for anti-emicizumab antibodies. In the pooled HAVEN clinical trials, 3.5% of patients (14/398) tested positive for anti-emicizumab antibodies and <1% (3/398) developed anti-emicizumab antibodies with neutralizing potential (based on declining

methods) - eg. VWF antigen
• Genetic tests of coagulation factors (eg. Factor V

Leiden, Prothrombin 20210 mutation)

pharmacokinetics). One patient from HAVEN 2, who developed an anti-emicizumab neutralizing antibody, experienced loss of efficacy after 5 weeks of treatment. There was no clinically apparent impact of the presence of anti-emicizumab antibodies on safety. To date,

more than 1100 persons with hemophilia, with and without inhibitors to factor VIII have been treated with emicizumab worldwide.

b. The development of an anti-drug antibody to emicizumab is distinct from the development of an inhibitor to factor VIII. Notably, anti-drug antibodies directed against emicizumab may affect how it works in the patient but will not affect the person’s underlying hemophilia or inhibitor status, nor the ability to manage bleeding events with their conventional therapies, including bypassing agents.

c. Continued diligence in evaluation of clinical efficacy of emicizumab as would be expected for any hemophilia therapeutic. Loss of efficacy of emicizumab may be manifest by an increase in breakthrough bleeding events. Patients concerned about a loss of efficacy should seek prompt evaluation by their provider.

d. We have provided information on assays that may be utilized for evaluation of the activity of emicizumab, utilizing a chromogenic factor VIII activity assay with human reagents that are recognized by emicizumab. However, the widely available conventional aPTT
and clot-based factor VIII activity assays can be used in evaluating a case of loss of efficacy. The aPTT should be within the normal range in all persons with hemophilia when obtained during ongoing treatment with emicizumab; similarly, clot-based factor VIII activity assays will be well above the normal range. In the course of evaluating a reported loss of efficacy,

a prolonged conventional aPTT assay and/or a low factor VIII activity (by clot-based assay or chromogenic assay using human reagents) in a person treated with emicizumab should be a useful initial evaluation for the presence of a neutralizing anti-drug antibody directed against emicizumab. Additional information regarding laboratory assays may be found within the prescribing information.

e. There are no commercially available assays in the US for determination of anti-drug antibodies directed against emicizumab. Should a patient and provider have suspicion of an anti-drug antibody outside of the ongoing clinical trial program, they should contact the manufacturer (https://www.gene.com/contact-us/ submit-medical-inquiry) for guidance on subsequent evaluation.

f. Recommend that patients and providers continue diligence in reporting any unanticipated adverse events. Available reporting mechanisms can be reviewed here (https://www.fda.gov/Drugs/ GuidanceComplianceRegulatoryInformation/Survei...)

2. Recommendations on surgical management with emicizumab

Emicizumab is approved for prophylaxis but how this extends to surgical prophylaxis remains to be fully understood. While it improves hemostasis, it does not normalize hemostasis. This is especially important when planning hemostatic control in the surgical setting. Within the clinical trials, some patients had adequate hemostatic control with emicizumab alone for minor surgical procedures while others did not. This is similar to what has historically been seen in patients with mild hemophilia.

a. Surgeries should be conducted at centers with appropriate experience and access to necessary laboratory monitoring assays for concomitant use of hemostatic agents

b. Elective surgeries should be conducted after patients have completed the loading dose phase and are at steady state maintenance dosing.

c. Emicizumab alone should not be presumed to be adequate for major procedures where current standards of care are to maintain factor levels within the normal range for a period of days.

d. Close monitoring of bleeding control as well as access to appropriate laboratory assays to monitor therapy (eg. chromogenic FVIII assay with FVIII replacement) is very important when determining treatment plans for patients on emicizumab needing surgical procedures.

e. For major surgeries and procedures where bleeding could result in serious complications, patients should be provided rFVIIa or FVIII replacement pre- and post- operatively to maintain adequate hemostasis at the discretion of the treating physician. Further research/ experience is needed to form better defined treatment plans for different surgical procedures.

f. Providers are cautioned to consider that bleeding complications from surgeries in hemophilia patients still greatly outweigh thrombotic complications in frequency and morbidity/mortality.

3. Recommendations on concomitant use of emicizumab during immune tolerance induction.

There are no clinical data on the concomitant use of emicizumab prophylaxis during immune tolerance induction (ITI). There has been significant academic debate as to the need for ITI with the availability of emicizumab (and other novel therapeutic agents
under continued investigation). There is considerable uncertainty as to the implications of persistent factor
VIII inhibitors in PwHA given the degree of efficacy for bleed protection provided by emicizumab. Nevertheless, MASAC recommends that the pros and cons of the various approaches for a PwHA and inhibitors be part of a patient/clinician shared decision-making and ITI should remain an option for their care. We also recommend that long term follow up and interventional trials that include the concomitant use of emicizumab with ITI should be encouraged. If ITI with concomitant emicizumab prophylaxis will be pursued we provide the following recommendations:

a. No more than 50 IU/kg per dose be administered unless observation will occur within a clinical trial. This relates to the uncertainty as to any potential incremental risk of an elevated FVIII level, even transiently, in patients on emicizumab who may need treatment with a BPA for breakthrough bleeding during ITI.

b. Data on the use of emicizumab prophylaxis with ITI should be conducted under a clinical trial or as part of existing databases collecting data on the natural history of emicizumab use within the US.

4. Other unresolved issues and potential new avenues of research

a. MASAC recognizes the potential utility of emicizumab prophylaxis in patients with severe Type 3 von Willebrand disease with inhibitors to von Willebrand factor

b. ATHN7 is a prospective observational study collecting data on the use of emicizumab within the US patient population and we strongly encourage that the availability of this study be discussed with patients who are prescribed emicizumab

c. We encourage additional investigations to determine potential safe and efficacious dosing of aPCCs with concurrent emicizumab

d. We encourage the continued accumulation of management of surgical experiences in patients prescribed emicizumab

e. There is insufficient data on the level or protection provided by emicizumab prophylaxis to patients who participate in high impact activities/organized sports and MASAC encourages additional research to study this.

5. Additional patient education recommendations

a. Revised ER and travel letters that include:

i. information that the patient is on emicizumab prophylaxis

ii. the potential impact on laboratory assays and acute bleed management

iii. Contact information for the HTC

b. Provision of dosing cards that detail the dose and frequency of FVIII concentrate or BPA for management of breakthrough bleeding

c. Instructions on when to call the HTC d. Instructions on Travel

i. Revised travel letter as detailed above

ii. Need to travel with appropriate dose of FVIII concentrate or BPA agent to manage breakthrough bleeding

References:

1. https://www.gene.com/download/pdf/hemlibra_prescribing.pdf

2. https://www.emicizumabinfo.com

3. Lenting PJ, Denis CV and Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood (2017) 130(23):2463-2468.

4. Young G, Callaghan M, Dunn A, Kruse-Jarres R and Pipe S. Emicizumab for hemophilia A with factor VIII inhibitors. Expert Rev Hematol (2018) 11(11):835-846.

5. Oldenburg J,Mahlangu JN,Kim B,Schmitt C,Callaghan MU,Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med (2017) 377(9):809-818.

6. Mahlangu J, Oldenburg J, Callaghan MU, Shima M, Santagostino E, Moore M, Recht M, Garcia C, Yang R, Lehle M, Macharia H, Asikanius E, Levy GG, Kruse-Jarres R. Bleeding events and safety outcomes in persons with haemophilia A with inhibitors: A prospective, multi-centre, non-interventional study. Haemophilia (2018)

7. Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jiménez-Yuste V, Kempton C, Dhalluin C, Callaghan MU, Bujan W, Shima M, Adamkewicz JI, Asikanius E, Levy GG, Kruse-Jarres R. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med (2018) 379(9):811-822.

8. Chromogenic factor VIII with human reagents: https://www.aniara.com/PROD/a221402-ruo.html

TRANSITIONING from High School to College or Work

by Lisa Cosseboom, M.Ed. & CAGS School Psychologist & Special Education Evaluation Team Chairperson

Published: Lifelines for Health Spring 2019

Most transitions can cause stress but transitioning from high school to college can be a scary one! In high school, the laws require that staff identify a student with a disability. Higher education is not required to identify students with disabilities. At the college level, it falls upon the student to be their own advocate. This may be difficult for some parents who have been used to being their child’s advocate for 17+ years! Because of privacy laws (FERPA), parents do not have access to their children’s records or are able to make decisions for their child. It is important that students with disabilities begin to advocate for themselves in high school so that they learn how to navigate difficult situations.

The American with Disabilities Act (ADA), section 504 requires colleges who receive federal funding to
provide equal access and reasonable accommodations to a student with a disability. Many private higher education institutions do not receive federal assistance and therefore do not necessarily have to offer a student with a disability, accommodations. However, even if a college is exempt from Section 504 requirements, a student may be covered under other disability rights legislation.

Here are some examples of accommodations that may be available at the college level:

• Use of note-takers for class lectures

• Making audio recordings of lectures

• Use of a laptop computer in the classroom

• Taking exams in a distraction-reduced room

• Accessible testing locations

• Course substitutions

• Accessible software

These accommodations are not automatically given to a student with a disability. The student must seek out and apply for reasonable accommodations through the college’s disability services department. A student does not need to disclose that they have a disability when applying to college. Once a student begins at a college, they will want to go to the Disability Services Center at the university. Be prepared to have supporting documentation of the disability. Each college has their own documentation requirements. Some examples may include a high school 504 plan, doctors’ documentation etc. However, keep in mind that the documentation must be recent (generally within 3 years). It is highly recommended that families review colleges’ disability services prior to choosing which institution will best support their child’s educational future.

Vocational Rehabilitation for People with Disabilities

The Federal Programs of Social Security Disability Insurance (SSDI) and Supplemental Security Income
(SSI) offer many options for services. Each state receives funding from these federal programs that are distributed into state programs. If a person is already receiving either SSDI or SSI, they are automatically qualified to receive Vocational Rehabilitation (VR) services. Vocational Rehab services include preference evaluations, job training and job placement. The mission of VR is to assist an individual in receiving the support they need and guidance to access that support.

To qualify for Vocational Rehabilitation, an individual must have a physical or mental condition that causes a “substantial impediment” to work and be able to benefit from VR services to gain employment. Each state has their own processes and procedures. When researching, look into your state’s Department of Health and Human Services or Education Department.

• a personal assessment of your disability(ies) to see if you are eligible and to determine how VR can help you

• job counseling, guidance, and referral services

• physical and mental rehabilitation

• vocational (job) and other training

• on-the-job training

• financial assistance while you are getting some vocational rehab services

• transportation needed to get to some vocational rehab services

• help transitioning from school to work (for students)

• personal assistance services

• rehabilitation technology services and devices

• supported employment services, and

• help finding a job

In my home state, Massachusetts, Vocational Rehab services are administered under the Massachusetts Rehabilitation Commission (MRC). They explain that “Vocational Rehabilitation (VR) helps people with physical, psychiatric, and learning disabilities find and keep a job.
VR helps you identify job goals based on your interests and skills and explore college and vocational training. It also reduces or removes barriers to employment. Priority is given to people who have the most severe disabilities in areas such as communication, mobility, work tolerance, and work skills.” Similar to applying for disability services in college, documentation including school records, medical history, evaluations etc. are required to become eligible for services.

Helpful links: http://www.askearn.org/state-vocational-rehabilitation-agencies/ https://www.ssa.gov/benefits/disability

ATHN 7 Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People With Hemophilia

by Janet Brewer, M.Ed  ClinicalTrials.gov identifier (NCT number): NCT03619863

Published: Lifelines for Health Spring 2019

The American Thrombosis and Hemostasis Network has initiated the Natural History Study for the purpose of following patients with Hemophilia A/B with or without inhibitors for a period of 4-6 years who receive their care from hemophilia treatment center physicians across the United States. The primary purpose of the study is to assess the safety of FDA-approved treatment products and their outcomes to include: replacement clotting factor products, bypassing agents and non-factor products. Treatment regiments will be at the discretion of the patient and their hemophilia caregivers. There will be no treatment products or compensation offered; inhibitor testing however, will be provided by the CDC at no cost to patients.

Data collection will include eligibility, demographics, medical history, hemophilia history (genotype and family history), inhibitor history and immune tolerance induction (ITI) treatment regimen (if applicable), co-morbidities at baseline (i.e., HIV, Hepatitis C), detailed treatment product(s) usage, bleeding events, surgical procedures, and *EUHASS adverse events and other adverse events of special interest. Data collection will also include patient- reported outcome questionnaires regarding health-related quality of life, treatment use and patient perceptions of treatment products. Patients will be seen at baseline, annually, and at study exit. Patients will also receive routine quarterly follow-up phone calls from HTC staff to review medical history, bleed events, and product treatment history.

A number of sub-studies are planned with pharmaceutical sponsors to collect information from patients about their specific product use. Participation in these sub-studies (Product Specific Modules) is optional and sub-study visits will be planned to coincide with HTC visits. The modules will collect information from patients about their perception and use of treatment products, physical activity levels and other general health questions. This data will be collected via questionnaire.

(https://clinicaltrials.gov/ct2/show/NCT03619863)

Secondary outcome measures will include:

• Effectiveness of non-factor products, bypassing agents and clotting factor replacement products based on the participant’s number of bleeding events and/or annualized bleed rate (ABR).

• Dosing regimens for hemophilia treatment products and total amount utilized for prophylaxis and treatment of bleeds.

• Target joint monitoring

Real world effectiveness of treatment products as measured by the number and types of medical visits and/or hospitalizations per year.

The study is currently open to 280 participants in 38 ATHN-affiliated HTCs. Patients will be seen at baseline, annually and at study exit.

Criteria:

• No age restrictions

• Open to men and women

  Inclusion Criteria:

1. Congenital hemophilia A or B of any severity with
   or without inhibitors, receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility;

2. Able to give informed consent (by patient or parent/ authorized guardian); and

3. Co-enrollment in the ATHN dataset

Exclusion Criteria:

1. Presence of any known bleeding disorder other than congenital hemophilia A or B;

2. Presence of concurrent hemophilia and a second hemostatic defect (low Von Willebrand Factor (VWF) without Von Willebrand disease (VWD) diagnosis is not excluded); and

3. Unable or unwilling to comply with the study protocol

Contact:

Angela Riedel - Ph: 309.361.4375, ariedel@athn.org 

Primary Investigators are:

Tyler Buckner, MD, MSc
Hemophilia and Thrombosis Center/ University of Colorado Anschutz Medical Campus

Nikki Hirsh, MS, CCRC - nhirsh@athn.org

Michael Recht, MD, PhD

The Hemophilia Center at Oregon Health & Science University

For a list of the 38 study locations please refer to:

Nikki Hirsh, MS, CCRC - nhirsh@athn.org

Michael Recht, MD, PhD

The Hemophilia Center at Oregon Health & Science University

https://clinicaltrials.gov/ct2/show/study/NCT03619863?show_locs=Y - locn

*EUHASS adverse events include: : death, factor inhibitor development, venous thrombosis, allergic reactions, treatment- emergent side effects, new malignancies, cardiovascular events, and blood-borne infections. Other treatment-related events to be documented on the ATHN Adverse Event Module Form including thrombotic microangiopathies, injection site reactions, drug-induced liver injury and anti-drug antibodies.

Advocacy to Protect PATIENT ASSISTANCE

by James Romano Dir. of Government Relations

Published: Lifelines for Health Spring 2019

Since the passage of the Patient Protection and Affordable Care Act (Public Law, 111-148) the pendulum has swung on the perception of patient assistance programs. Once a beacon of hope in the social safety net, governmental sympathy and stakeholder interest has largely vanished. Today the conventional wisdom for these programs have oscillated between the false theory that these programs are somehow no longer necessary or needed to the dangerous notion that patient assistance actually hurts patients. Health Insurance Providers in their quest to reduce their costs and maximize profits have influenced and benefited from the pendulum shift. The health insurance industry will not be satisfied until as many patients with rare disorders and chronic conditions are forcibly transitioned onto public programs such as Medicare and Medicaid.

Patient Services Incorporated has met the challenge
laid down by the much larger health insurance industry in an attempt to protect the patient assistance model that
the organization founded 30 years ago. PSI is a national nonprofit patient assistance organization that raises private donations into disorder specific programs. PSI utilizes those donations to provide financial assistance to patients to subsidize the high cost of health insurance premiums; out of pocket expenses such as deductibles, copayments and co- insurance; as well as ancillary supplies and travel expenses. PSI also helps patients to obtain their disability benefits for certain conditions through our ACCESS Program.

This Pendulum shift first manifested itself approximately 5 years ago in 2014 with the rule promulgated by the Centers for Medicare and Medicaid Services (CMS) entitled: Patient Protection and Affordable Care Act: Third Party Payment of Qualified Health Plan Premiums. This rule mandated that health insurance providers in the state and federal insurance marketplaces accept insurance premium and cost sharing assistance from State Ryan White/HIV Programs; Indian Tribes & Tribal Organizations; as well as any other government program. The rule also states that health insurance providers can impose contractual prohibitions onto any other entities such as nonprofit organizations like PSI. This rule serves to undermine the reform of the pre-existing condition exclusion included in the Affordable Care Act because this policy disproportionately affects those with rare and chronic illnesses who rely on these programs to obtain needed treatments and therapies while maintaining their way of life.

Since the release of the rule over 100 plans in 43 states have implemented the prohibition. Insurance providers have gone to the extremes while implementing this prohibition including threatening patients with litigation to recoup claims and forcing patients to sign attestations under the penalty of perjury that the patient receives no outside support in paying their premium. The target of this nefarious rule are people with rare and chronic conditions living their lives as best they can while Health Insurance providers are developing ways to prevent them from obtaining the needed treatments. Even though PSI has fought to modify or overturn the rule, the insurance industry has been emboldened in their actions and have attempted to spread the prohibition into other insurance coverage markets including the Medicare Supplement/ Medigap market as well as Non-ACA individual market. Besides the CMS Rule, health insurance providers have looked for other creative ways to limit access to specialty treatments for patients again placing profits above lives. The implementation of Copayment Accumulators; Fail First policies and prohibitions on copayment cards by manufacturers are examples of this creativity to push more costs onto patients. These initiatives have one common thread running through them—ensuring that patients must jump through more hoops to obtain their treatment or worse preventing the access of treatments all together. PSI has stepped forward to defend the patient assistance model we created. The mission of PSI in the advocacy field has been to advocate for government policies at the state and federal level that will end these egregious practices and ensure easier access for patients living with rare and chronic illnesses.

PSI was the first organization to recognize the threat the CMS rule would pose to patient assistance. PSI has led the advocacy efforts over the last five years to overturn this rule. PSI created the Marketplace Access Project Coalition to bring together like-minded patient advocacy groups to support legislative efforts to help patients utilize these programs. PSI was successful in developing the Access to Marketplace Insurance Act (HR 3742 & HR 3976), a bill that has been introduced in the last two Congresses by Kevin Cramer (R-ND). Congressman, now Senator, Cramer recognized the need to strengthen the social safety net not diminish it and coined our battle cry—Let Charities be Charitable. This legislation would amend the Affordable Care Act and add three more entities to the list that CMS established through the rule. Health insurance providers must accept premium and cost sharing assistance from the entities stated in the rule but also three additional entities-- Non-Profit Organizations; Places of Worship and Civic Organizations. The legislation had strong bipartisan support and garnered 147 and 177 cosponsors respectively in Congress. However, the health insurance plans worked overtime to prevent the legislation from passing.

Since 2012, PSI has hosted our yearly advocacy fly-in to promote the model and assistance programs. PSI brings patients from all over the country to advocate with their Members of Congress and Senators on the importance of the patient assistance they receive and what would happen if that assistance was limited or even prohibited. To continue to advocate for assistance for patients, PSI is partnering with other entities such as the Hereditary Angioedema Association; the Pulmonary Hypertension Association and Good Days to form the coalition—United for Charitable Assistance. UCA will work on the state and federal levels to promote and protect charitable assistance for patients for many years to come.

PSI has worked to understand why CMS has promulgated such a rule. CMS has stated that they are concerned that charities would flood the plans with sick patients—contrary to the stated goals of the Affordable Care Act. PSI has worked with Congress through the House and Senate Appropriations Committees to include report language in the FY 2016 and FY 2017 Joint Explanatory Statements, asking the agency to explain to Congress its reasoning for excluding nonprofit organizations from the listed entities. CMS ignored the request for information from Congress and never provided any explanation. Congress continued to press the issue sending at least six sign-on letters including the signatures of hundreds of Members of Congress asking for CMS to modify the rule. To this moment CMS has ignored Congress and has ignored the calls from the patient advocacy community to fix this rule.

PSI will continue its leadership in passing the Access to Marketplace Insurance Act as well as promoting charitable assistance in Congress and in state legislatures. If you would like to become involved, please contact the PSI Government Relations team at Advocacy@uneedpsi.org.

Since the authorship of this article, we have the following updates to add.

In March 2019, Virginia and West Virginia became the first two (2) states to ban copay accumulators. Several states, AZ, CT, IN, KY and RI, have pending state legislation to ban as well!

On April 18th, CMS released their Notice of Benefit and Payment Parameters Rule for 2020, which limits use of brand name drugs that have equally effective generics. Because factor does not have a generic alternative, it should be exempt from the Accumulator Adjuster.

https://www.cms.gov/newsroom/press-releases/cms- issues-final-rule-2020-annual-notice-benefit-and-payment- parameters

Editor’s note:

Please view the PSI You Tube Accumulator Adjustor video on this topic:

https://video.search.yahoo.com/yhs/search?fr=yhs-sz-002&hsimp=yhs-002&hsp art=sz&p=PSI+you+tube+accumulator+adjustor - id=1&vid=563fcff548e5a6ed0b 912afc8cc8247f&action=click

or NHF’s YouTube video

https://www.hemophilia.org/Newsroom/Advocacy-Legislative-News/Copay- Accumulator-Adjustments-What-are-they-and-how-they-can-affect-you

How Mindfulness Keeps Us in the MOMENT

by Krystyn Strother

Published: Lifelines for Health Spring 2019

Have you ever heard the saying “don’t let the future steal your present,”? Consider it for a moment. This statement holdsso much potency. Many of us could benefit from repeating these words as it shows the importance and power of mindfulness. If you have never heard of mindfulness before, it is the practice of being present in the moment.

The Importance of Staying Present in the Moment

Simple in concept, more challenging in practice, mindfulness allows us access to live in the moment, and the tools to cope with those moments when they may be undesirable. When we spend our time dwelling on the past or worrying about the future we cultivate anxiety, worry, stress, and fear. These emotions can contribute to problems with sleep, immunity, and mental health, to list just a few. One negative thought typically triggers another and another and so on, initiating a domino effect that can lead you into a spiral of thoughts.

One way to keep those thoughts at bay is through mindfulness. Mindfulness allows you the opportunity to quickly recognize these thoughts and anchor to the present moment. Worry is generally about the future, sometimes the past, and it is near impossible to be anxious or worried when your mind is focused on what is simply happening in the present moment.

“Don’t let the future steal your present.”

Navigating the What If’s

Go With the What Is. When you or your child has a chronic illness, it may seem impossible to not worry about what the future holds. When the mind isn’t dwelling on the future it can often get stuck in the past, ruminating over past mistakes. The what if’s of the past and future Keep us disconnected from the present. We can’t change the past, so why live in it? There are no guarantees for the future so why jump to conclusions? Of course, it is human nature and wise to plan for the future. It is also smart to learn from our past mistakes. However, it is irrational and potentially detrimental to worry about that over which we have no control – e.g., the past and the future.

Living in the moment allows us to be present, mindful, and experience the passing of time. Whatever emotion or thought or physical sensation you are experiencing, whether positive or negative, over time, has to pass.

Practical Tips for Everyday Mindfulness

Pay attention. It’s hard to slow down and notice things in a busy world. Try to take the time to experience your environment with all of your senses — touch, sound, sight, smell and taste. For example, when you eat a favorite food, take the time to smell, taste and truly enjoy it.

Live in the moment. Try to intentionally bring an open, accepting and discerning attention to everything you do. Find joy in simple pleasures.

Accept yourself. Treat yourself the way you would treat a good friend.

Focus on your breathing. When you have negative thoughts, try to sit down, take a deep breath and close your eyes. Focus on your breath as it moves in and out of your body. Sitting and breathing for even just a minute can help.

Some of the same things that can quickly disconnect us from the present moment can
also serve as a reminder for you to return to the moment. Make your mobile phone or computer your mindfulness machine by setting reminders that go off through the day to encourage you to notice the moment.

When the reminder goes off, stop whatever you are doing for thirty seconds and focus your awareness on the present moment. What is happening right then? What is the temperature? How are you breathing? What do you taste? Check in with yourself and ask yourself about how you are feeling emotionally and physically, and what you are thinking about. Mindfulness is all about being accepting, non-critical and open, so be kind to yourself and curious about your experience.

How do you attain mindfulness? There is no definitive “achievement” of mindfulness, especially when the essence of it is to empty your mind. Mindfulness is just a state of being. Use the times when you are feeling worried or anxious as an opportunity to return to the present moment. Remind yourself that regardless of what happens in the future, you will be able to handle it. After all, you always have been able to handle whatever life has thrown at you. You are resilient. You are strong. You are capable.

Krystyn Strother is the former program director at HUSH Meditation, strategic designer/authorof the HUSH meditation curriculum, is a certifiedmeditation instructor, co-founder of NOMAD, “Adventures in Wellness”, and yoga instructor. Krystyn’s yoga classes range from Vinyasa to Yin. In addition to her regularly scheduled classes, Krystyn guest teaches at several yoga teacher training programs throughout the country, speaks at conferences on mindfulness and stress reduction practices, teaches specialized workshops, facilitates yoga + adventure retreats, and conducts continuing education classes for currently registered RYTs. Krystyn holds a certificate of completion in the Yoga of Awareness For Chronic Pain, an evidence-based program sponsored by the Department of Anesthesiology at OHSU.

Read more about Krystyn at krystynstrother.com

Outstretched Wings are Good for Soaring

By: Barb Forss

Published: Lifelines for Health Summer 2020

You’ll probably never meet another Woman With a Bleeding Disorder (WWBD.) There just aren’t that many of you out there.” These were the words of the hematologist who diagnosed me in 1998 with severe, hereditary, FVIId. At age 47.

Fortunately for me, the words “no”, “never” and can’t” aren’t an integral part of my vocabulary. So, I was determined to find someone who bled like me, ANYONE, who could give me advice, support, friendship, and most of all, help me feel normal and not so alone.

Before computers, cellphones, and social media were around, resources and connection opportunities were limited. After attending a training session by NHF called “Woman to Woman”, I was propelled into the direction i needed to go. I needed to the comfort of being with other WWBDs and in 1998 LadyBugs was formed for all women with a bleeding disorder.

Slowly at first, then gaining momentum, LadyBugs gathered in cities in my state, mostly as social opportunities. Luncheons or teas, anyplace we could meet and tell our stories. Those stories were important, because they told us that not only were WWBDs not being properly diagnosed, but there was also a general lack of knowledge about treatment options.

One year, we actually had our very own special “Meet and Greet” session at NHF. How amazing to finally be able to give LadyBug Hugs to those I’d only written to or spoken with on the phone! We all felt like long-lost sisters thinking, finally...here’s somebody who “gets it and gets me”. Tears of joy were often mixed with tears of compassion upon hearing each other’s bleeding stories and corresponding treatment or, as was sadly more often the case, a lack thereof.

Flash forward almost 22 years, and with the amazing support of CHES, the LadyBugs Program, which started
as a grass-roots endeavor to just meet up with others like myself, is now the only program to hold a dedicated annual, national retreat for all WWBDs ages 16 and up. Women who have any bleeding disorder, including carrier mothers, sisters and daughters of men and boys, qualify to be a “LadyBug”.

LadyBugs encourages WWBDs to recognize and advocate for the care they need. Sometimes there are obstacles. That’s why our Retreats are literally loaded with experts from all types of beneficial disciplines. We have sessions with those who are experts at treating WWBDs... hematologists and OB-GYNs, nurses teaching us self- infusion, and yoga instructors showing us how to lower our shoulders from our ears and b-r-e-a-t-h-e. Mental health experts reminding us it’s ok to say “no” and not feel bad about it. We added an exciting one of a kind study component in 2019, and 2020 for women ages 18-50 with factor deficiencies to participate in the Assessment of Joint Arthropathy Using Ultrasound Technique in Women with Coagulation Disorders (WUP- Women w/ coag disorders Ultrasound Project) facilitated by Fernando Corrales-Medina, MD, and Kelli Fraga, DPT-PI/ Investigators and Joanna Davis, MD, Co-Investigator of the University of Miami.

WWBDs have glowing reports with statements like, “I learned more about my disorder here than ever before!”,“Thank you for empowering me to advocate for myself”, and “I like the intimacy
and just women involved. It provides a support system to expand our awareness and education to advocate for ourselves and families.” Probably the number one comment we hear at LadyBugs Retreats is, “This is life- changing for me. I can’t thank you enough.”

The LadyBugs Retreats are making a difference in the lives of hundreds of women living with SHEmophiliaTM, thanks to the generous support of CHES, nSpiration, and the companies who help fund their programs. If you’re interested in learning more about our Retreats, reach out at: https://nSpiration.foundation/ladybugs

We also have a closed group on FaceBook where we chat. And no worries, no one will ever try to sell you a product or service, and your name and stories are protected.

Now don’t forget to give out those LadyBugs Hugs!

F7 and GT Merging Update: One Drop RBD Consortium

Published: Lifelines for Health Summer 2020

In 2012, CHES began serving the needs of those affected by FVIId at a small venue in upstate New York with 18 families in attendance; in 2019, we welcomed 55 families! It was the very first national conference ever held in the US that catered specifically to their needs. As we reflect on the impact this program has had for those with FVII deficiency, the milestones are astounding. This community has gone from not being sure what a HTC was, or how to self-infuse, or knowing another person with their deficiency, to a robust, empowered family community. The Super Sevens, as they call themselves advocated from the very first Factor 7 Retreat for more research to understand their disorder. In 2017, that call was answered when Dr. Diane Nugent and her team from Children’s Hospital of Orange County, CA attended the retreat to conduct blood samples from every biologically related member of a family for the purpose of identifying molecular variants. The gathering of this information has provided further insights in regard to discrepancies between circulating FVII activity and bleeding symptoms, which often do not correlate.

What's with the name? One Drop refers to the extremely low prevalence of FVIId individuals (said to be 1:500,000), those with GT (1:1,000,000), and others with rare factor deficiencies. Equally important, but small in numbers, hence the name - a drop in the bucket, er pool, er ocean. In parallel, the droplet is a symbol of blood - an obvious choice for these groups.

In 2016, CHES was thrilled to begin a collaboration with Helen Smith, founder of The Glanzmann’s Research Foundation for the first Glanzmann’s Thrombasthenia Symposia. A tireless advocate, Helen created a global community of families affected by this one in a million-bleeding disorder. It was an honor to bring 35 families from across the country together to meet others managing the same challenges that Glanzmann’s brings. Like our Factor 7 families, many had never met another person with GT. We were thrilled to see our families again in 2019 for a second GT Symposia. Dr. Nugent and her team were able to join this group and obtain blood samples for additional research for this ultra- rare disorder.

So, what is One Drop? In 2020, nSpiration Foundation will collaborate with CHES to combine the Factor 7 Retreat and GT Symposia into one rare bleeding disorder consortium named One Drop. There will
be separate in-depth medical sessions for each disorder facilitated by physician experts in these fields. Self-Infusion classes, and sessions on the psychosocial effects of chronic conditions, focus on women’s OB/Gyn needs, and connecting through shared experiences. Teens participate in their own dedicated track that provides time with medical specialists, team building and rap sessions. One Drop will offer two study opportunities this year to include Dr. Nugent’s current molecular sequencing project for all biologically connected family members, as well as The Assessment of Joint Arthropathy Using Ultrasound Technique in Women with Coagulation Disorders (WUP- Women w/ coag disorders Ultrasound Project) for women ages 18-50 with a factor deficiency.

One Drop is scheduled for Sept. 11-13, 2020 in Detroit, Michigan. Due to COVID-19 however, we are closely monitoring and will abide by federal, state, and city guidelines meant
to keep everyone safe. Possible contingency plans include postponing to a later 2020 or 2021 date, or a virtual
meeting.

Tragically, Helen Smith unexpectedly passed October 20, 2019. The GT community mourns as she was highly regarded and loved by all. CHES sends its deepest condolences to her family. Helen's efforts as founder of The Glanzmann's Research Foundation continue on in her memory. Donations can still be made at: https:// www.gofundme.com/f/glanzmann039s-research

For more info on One Drop, visit nSpiration.foundation/one-drop

A PARADIGM SHIFT for WOMEN with Bleeding Disorders

A PARADIGM SHIFT for WOMEN with Bleeding Disorders

By: Robert Francis Sidonio, Jr., MD, MSc.

Published: Lifelines for Health Summer 2020

Women and Girls Clinics

The recognition of the unique challenges of women with bleeding disorders has quickly expanded over the last 2 decades. In 1998, a seminal article was published by Dr. Peter Kouides highlighting the “silent majority” and setting the stage for the hard work needed to meet these challenges. Back then we knew that it would take a wider medical community to address the needs of women with bleeding disorders (WWBD).

The focus has been to increase awareness amongst healthcare providers focusing first with the hematologists and then other medical providers that are an essential part of a woman’s healthcare including adolescent medicine, gynecology oncology, and primary care providers. Additionally, because of large gaps in care, a multidisciplinary approach would be required. It made sense that the same approach used successfully for men with bleeding disorders, specifically males with hemophilia, would be ideal for WWBD. Modifications of this model were needed of course. This multidisciplinary team that was in place for decades as part of the hemophilia treatment center (HTC) model and established a solid foundation for the creation of the first “women and girls clinics.” Typically, the clinic model employed a hematologist, nurse and gynecologist or adolescent medicine provider. As with the multidisciplinary HTC model, social workers, genetic counselors, and physical therapists are added as available and needed. Most of these women’s clinics are conducted on a recurrent basis, typically once or twice a month. The approach may vary slightly based on hospital or clinic infrastructure. The patient may be seen separately by the hematologist and gynecologist/adolescent medicine provider or together, my preferred strategy. To make this model work from a financial perspective, the gynecologist or adolescent provider may have a portion of their salary covered utilizing 340B funding, a program created by Congress allowing the HTC to purchase clotting factor concentrates (CFCs) at a discount price with the savings going directly into providing services for the patient, including paying for the salaries of the HTC staff and clinical research initiatives.

Thankfully, more patients are being identified and managed with expertise improving. This is seen in the number of patients registered in various surveillance programs such as the CDC Community Counts and ATHNdataset. All of these collect basic demographic data and limited information on bleeding events and diagnostic labs and in some cases limited information on quality of life, or the affect the bleeding disorder has on the person’s life. There are some targeted initiatives that have been ended such as Female Universal Data Collection which summarized data on >300 WWBD from 17 HTCs from 2009-2011. Similarly, the My Life our Future Project had a pilot allowing collection of clinical bleeding symptoms and genetic testing in >1000 hemophilia A and B carriers. Ongoing research projects will be discussed later in this article. As a result of more focus on WWBD, the number of women and girls clinics has grown from a handful in the early 2000s to >150 in 2020. These clinics offer a variety of services for WWBD and best practices are currently shared at yearly Learning Action Network meetings sponsored by the Foundation for Women and Girls with Blood Disorders.

Following a few articles in the early to mid 1990s highlighting our lack of ability to address the needs of WWBD, from 1990-2010 there was an exponential rise in the number seen at HTCs at a much higher rate than their male counterparts. It is reassuring that to see the general trend of WWBD being managed by the same top-notch hemophilia providers as their male counterparts. But are their clinical and research needs

being met?

Despite all of the aforementioned progress, there is certainly a gap in the recognition that WWBD may have significant bleeding and a lack of standard practice in the management over their lifetime. The solution to this lies in an improved focus on clinical research in WWBD which over time will translate into improved care and recognition from some reluctant colleagues and payors.

Advocacy Organizations

The Foundation for Women and Girls with Blood Disorders (FWGBD) was launched in 2010 as a non-profit organization with a focus on provider education across all disciplines to ensure women and girls with blood disorders are diagnosed and appropriately managed over their lifetime. This organization has a robust group of mentored young physicians interested in clinical research and innovation in practice and has led to multiple research initiatives. Although the initial focus was on women and girls with bleeding and clotting disorders, blood disorders such as sickle cell disease, thalassemia, and immune thrombocytopenia are being addressed more over the last 3 years.

While FWGBD focuses on provider education and developing a medical community of dedicated researchers and master clinicians, patient advocacy organizations such as the National Hemophilia Foundation (NHF) and Hemophilia Federation of America (HFA) have dedicated programs to women and girls with bleeding disorders. Victory for Women (victoryforwomen.org) is an NHF initiative created to provide support, education, and resources for women and providers in the bleeding disorders community. The main goal is to address critical issues and ultimately improve quality of life for women in this tightknit community. It recently was rebooted with additional support. HFA has created a Women Bleed Too! Toolkit (hemophiliafed.
org) organizing their resources amassed over the years into one location. Acknowledging poor communication between providers and patients regarding the frequency and volume of heavy periods a smartphone app called Sisterhood (sisterhoodapp.com) was created to empower the patients to track their menstrual periods. Critical to improving awareness and educating the general public is collaboration. HFA and FWGBD created a brochure for providers highlighting the resources available and another brochure targeting the patients at risk for bleeding listing the typical bleeding signs and symptoms of a congenital bleeding disorder.

The NHF and the CDC collaborated on multiple materials focused on WWBD. The CDC has recently updated their materials and information on WWBD (cdc.gov) focusing on recently published research and the impact of a bleeding disorder on the lives of women with bleeding disorders. Betteryouknow.org is a website for undiagnosed women and men experiencing bleeding symptoms. The campaign was formed to create awareness and provide online resources to improve the time to diagnose a bleeding disorder. The materials are available from the CDC website and directly from betteryouknow.org.

The Canadian Hemophilia Society (hemophilia.ca) has long provided resources for WWBD and Code Rouge was a focused initiative to improve the time to diagnose a bleeding disorder for women with reproductive tract bleeding (heavy menstrual bleeding and perimenopausal bleeding).

To support their mission, they have meetings bringing together healthcare providers to educate, disseminate best practices, and debate controversial topics.

Focusing on the most common bleeding symptom in WWBD, Dr. Paula James (my personal clinical research hero) of Queens University created a website (letstalkperiod.ca) with an online version of bleeding score (ISTH Bleeding Assessment Tool) that allows at risk women to answer a brief bleeding inventory and determine whether they may be at risk for a bleeding disorder such as von Willebrand Disease. This sort of direct to patient initiative empowers women to advocate for themselves and arms them with objective bleeding information to approach their primary care provider or hematologist. Additionally, Dr. James’ initiative like the aforementioned organizations is deft at using social media to increase awareness.

List of Coagulation studies needed for WWBD

To appropriately evaluate the bleeding tendency of a woman or girl at risk for a bleeding disorder, the best first step is to objectively list the bleeding symptoms. One of the best methods to do this is to use the ISTH Bleeding Assessment Tool (ISTH BAT). This is available online via letstalkperiod.ca, academic website (bleedingscore.certe.nl), and the CDC.

A typical approach would be if there is an abnormal bleeding score (≥ 6 for females, ≥ 4 for males) a laboratory battery should be considered. This typically includes a CBC, PT and aPTT, Fibrinogen activity, and VWD profile of labs. The usefulness of the PFA-100 is widely debated and thus not routinely ordered. If this evaluation is negative, then it is reasonable to consider repeating the VWD profile particularly if the results are <100% and ordered with a platelet aggregation study (whole blood impedance or light transmission aggregometry.)

1. Complete blood count: Includes the hemoglobin and platelet count.

2. PT and aPTT: Prothrombin time and Partial thromboplastin time. This “bleeding time” can determine whether there is a significant reduction
   of certain clotting factors. It is limited in that mild reductions may be missed. FXIII deficiency will not be screened for using PT and aPTT.

3. Fibrinogen: This is a clot-based assay that can
   be used to screen for fibrinogen deficiency or dysfibrinogenemias. There is also a fibrinogen antigen that can be used if this activity assay is low.

4. Factor assays: Depending on whether there is a family history of a certain factor deficiency, individual factor levels may be sent. This includes FII, FV, FX, FXI, FVIII, FIX, FVII. FXIII is rarely sent due to the prevalence being less than 1 in 1 million.

5. VWD profile: This typically includes the VWF antigen (VWF:Ag) a functional assay (VWF:RCo or VWF:GPIbm) and FVIII (factor 8 activity). Often times this assay may need to be repeated particularly if obtained
when severely anemic or during illness. A number of additional studies that can be sent depending on the initial results of the above. Certain labs will use the VWF:CB (collagen binding assay) to screen for type 2 VWD instead of using multimer distribution evaluation (how the VWF looks on a gel and whether all portions of it are present).

6. If the above is negative and there is concern for a qualitative platelet disorder it is reasonable to consider sending platelet studies (typically whole blood impedance or light transmission aggregometry). Basically, these tests evaluate how well your platelets work and react to certain reagents.

RESOURCES

As part of largely collaborative efforts a significant number of resources for both healthcare providers and patients have been created.

CDC.gov has a fact sheet about symptoms of bleeding in WWBD

(Betteryouknow.org is a collaboration between NHF and the CDC)

1. Postcard advertisements focused in improving awareness of WWBD

2. Menstrual chart and scoring system (Pictorial Bleeding Assessment Chart)

3. Teen booklet focused on discerning between normal and heavy menstrual bleeding

4. Doctor visit preparation list to improve communication between provider and patient

5. Healthcare diary list to focus the conversation on bleeding symptoms and signs

6. Lab test log to compile a list coagulation studies that may have been obtained from various healthcare systems

7. Testing booklet that explains the various coagulation studies important for making an appropriate diagnosis of a bleeding disorder

LetsTalkPeriod.ca has an electronic online version of the self-BAT, a self-administered version of the ISTH Bleeding Assessment Tool) assigning a score determining whether a woman or girl is at risk for a bleeding disorder such as von Willebrand Disease

1. NHF (National Hemophilia Foundation - Hemophilia.org) includes MASAC's (Medical and Scientific Advisory Council) guidelines (#251 and 245) focused on perinatal care and general recommendations for WWBD.

2. Victory for women (victoryforwomen.org) website focused on supporting WWBD and creating a community for conversations and general support.

HFA (Hemophilia Federation of America
- HemophiliaFed.org) offers the Women Bleed Too! Toolkit includes HFA/FWGBD brochures focused on bleeding symptoms to help identify women with possible bleeding disorder and educational patient directed materials. Sisterhood smartphone app which is an electronic version of the PBAC (Pictorial Bleeding Assessment Chart)

1. FWGBD (Foundation for Women & Girls with Blood Disorders - FWGBD.org) has made collaborative efforts with HFA above

2. Library of published papers focused on WWBD and compiled guidelines and an “ask the experts” option

3. List of clinics and level of resources focused on women and girls with bleeding and blood disorders

Ongoing Research projects in WWBD

There are a number of ongoing clinical initiatives addressing WWBD and I will highlight a few. ATHENA1 is an ATHN DREAM Award project led by Dr. Kristina Haley focusing on characterizing WWBD enrolled in the ATHNdataset. Recently, she described nearly 9,000 WWBD in the largest cohort to date. Of note, it highlighted our need for better focus on medical management of heavy menstrual bleeding.

The VWDMin (Von Willebrand Disease Minimize Menorrhagia) study (NCT02606045) is evaluating the usefulness of Tranexamic acid and a VWF concentrate in the reduction of heavy menstrual bleeding in adolescent and adult women with low VWF and VWD. It is ongoing and led by Dr. Margaret Ragni
from the University of Pittsburgh. The University of Miami Hemophilia Treatment Center has an investigator-initiated surveillance study for women with any bleeding disorder between the ages of 16 – 40. The participants will complete a questionnaire, undergo a physical therapy evaluation, and have on-site ultrasound imaging of their knees, elbows and ankles (the “index joints”) with enrollment occurring at the National LadyBugs Women’s Summit presented by the nSpiration
Foundation in collaboration with CHES (Comprehensive Health Education Services.)

Unmet Research Needs

As I see it, there are a number of unmet needs in WWBD. I will highlight a few that I feel need to be addressed soon, and certainly there are more to address.

1. We do not understand how much a congenital bleeding disorder, such as VWD or hemophilia carriage, contribute to the severity or irregularity of heavy menstrual bleeding or any reproductive tract pathology. To that end we need to focus on the pathophysiology of uterine bleeding (period bleeding and menopausal bleeding). We do not know whether a bleeding disorder leads to anatomic defects or alteration of the blood vessel formation leading to irregular and prolonged periods.

2. We do not fully understand why there is a discrepancy in bleeding symptoms and severity of clotting factor deficiency. This is noted particularly in men with mild VWD and in rare bleeding disorders, but it seems to be more pronounced in WWBD. For example, we have not been able to determine why a woman with a FVII level of 35% may bleed more than one with a level of 5%, and why women with hemophilia and mild factor deficiency have similar bleeding tendencies as those with normal levels. Even more of a challenge is in those with low VWF and mild VWD. The range of bleeding is quite large and likely due to the multiple genetic causes of reduction of VWF in humans.

3. We are not able to accurately predict bleeding with day to day events and with procedures, particularly in those with very mild factor deficiencies. Larger prospective studies will be needed to address this issue.

4. The pathognomonic bleeding symptom of hemarthrosis in hemophilia is poorly described in hemophilia carriers and those with mild, moderate and severe deficiency. Better documentation and evaluation of treatment outcomes will ensure better communication between providers and patients.

5. We have not been able to prospectively evaluate the role of hemostatic agents and hormonal agents (birth control pills, IUDs, and progestin only pills) in the medical management of heavy menstrual bleeding. We have not been able to effectively conduct clinical trials in this group due to the inherent challenges of infusions of CFCs (clotting factor concentrates) at the onset of the period. The majority of persons with VWD do not know how to infuse (due to infrequent IV infusions in general), certainly a much lower rate than those with hemophilia. Currently the VWDMin study (NCT02606045) is evaluating the usefulness of Tranexamic acid and a VWF concentrate in the reduction of heavy menstrual bleeding in adolescent and adult women with low VWF and VWD. To date, no prospective study of the role of FVIII or FIX concentrate has been executed in hemophilia carriers, again due to the complexity of infusions on the first day of the period and lack of large enough participation.

6. We need further investigation of the role of imaging, such as musculoskeletal ultrasound and MRI in surveillance of possible joint damage/bleeding particularly in the women and girls with mild and moderate clotting factor deficiency – more specifically in hemophilia and VWD.

7. We need a more inclusive registry or surveillance system. Potentially we could leverage the resources of NHF and ATHN for better longitudinal evaluation and there will be an international effort with ISTH (International Society of Thrombosis and Hemostasis) soon to collect data on hemophilia carriers and VWD patients. Women and girls with bleeding disorders are currently part of the CDC Community Counts initiative (part of the ATHN data collection) and are included in the general authorization into the ATHNdataset. I believe a focused registry is needed to be able to answer some of the questions posed and to encourage larger scale participation.

With continued ongoing collaborative efforts from the patient advocacy groups, medical research societies, government, and pharmaceutical industry we can address the unique medical and research needs of WWBD. In my relatively short career, I have seen a concerted effort and only see continued dedication from the next generation of young investigators.

Dr. Sidonio is an Assistant Professor of Pediatrics, Emory University School of Medicine, Clinical Director of the CHOA Hemophilia Treatment Center, and the Associate Director of Hemostasis and Thrombosis, Department of Pediatrics, Children’s Healthcare of Atlanta. The focus of his clinical research career has been on understanding the prevalence of congenital bleeding disorders such as low VWF, qualitative platelet disorders or hemophilia carriage in adolescent girls and women with heavy menstrual bleeding and the diagnosis and management of women and girls with bleeding disorders. Dr. Sidonio has multiple national leadership and/or working group roles in every major hemostasis organization. Notably, Dr. Sidonio is the national PI for a recently awarded grant called ATHN 9 (severe VWD), Mexico Inhibitor Study (natural history of inhibitor development in Mexico) and Emicizumab PUP and Emicizumab ITI study.

Virtual Family Camp - Reaching for Normalcy

by Hanukkah “Rea” Watson

Published: Lifelines for Health Fall/Winter 2020

March has always been a memorable month for me and my family. It was the month we welcomed our oldest son Benjamin into the world over fourteen years ago. A traumatic circumcision led us to our diagnosis that came just in the nick of time. Stuck on an island at an overseas military base with a scarce supply of factor eight was just enough to save his precious life from slipping away! As new hemophilia parents that were just grasping the reality of what it would truly mean to raise a newborn son with a bleeding disorder, we found hope in the arms of a welcoming hemophilia community as we returned to the United States. This crazy journey rocked us to our core with so many ups and downs. It was not long into Benjamin’s young life that he would end up developing an inhibitor to add to his severe hemophilia A diagnosis.

We had the courageous honor of doing it all over again, when our second son, Brandon, was diagnosed with severe hemophilia at birth. The NICU team quickly tested his cord blood after a very scary C-section birth. Brandon developed an inhibitor as a toddler- just as his brother had. They both have witnessed countless days in and out of the hospital; joint injuries, line infections, ridiculous amounts of school absences as well as over a dozen surgeries between the two of them. With the help of so many organizations, support groups, a loving family, supportive friends and an awesome medical team, they have both overcome so many trials. This year was going to be one that we truly cherished, with Benjamin wrapping up middle school and preparing to enter high school. Brandon was getting exciting about walking through the doors of his middle school for the first time. Their little brother was over the moon about meeting his kindergarten class.

Little did we know that March of 2020 would bring a pandemic resulting in our kids’ return to home earlier than we expected. They were home for the last few months of those last school years before transitioning to middle and high school. Monumental steps! Home for all of the summer. What were we going to do? Well, in all honesty, I am not sure we were motivated to do anything but sit around with the exception of a few family bike rides as we realized that our summer vacation plans would eventually be cancelled... We ended up doing what felt impossible on most days and that was, try our best to create some sense of normalcy. I’m sure everyone’s’ “normal” looked different.

Then, to our surprise (after waddling in self-pity, utter despair and BOREDOM), we got an email from nSpiration/ CHES’ After the Shock Inhibitor Family Camp. We had never attended because our calendar was normally so congested with vacation plans to see family out of state. We were always aware of the resources and programs, but unfortunately, were never able to clear our schedule... Yeah, that may need to change once this all passes over!

We signed up for the Virtual Family Camp and CampFire Events, and I am so glad that we did! We were given a schedule of a variety of virtual programs for family activities! I somehow got my teenager to take part and actually talk about his feelings from breaking a cup and putting it back together with golden materials... it was so beautifully broken! I didn’t know a cup could speak, be so inspiring and meaningful without even saying a word!

We were able to connect with other inhibitor families. Some days things were so crazy, I had to turn off my camera and just listen and on other days I was able to be even
more engaged, but it was camp, nonetheless. We enjoyed the singing, laughing, creating and science experimenting and for the first time since COVID-19 hit our state, we had something that felt about as normal as things have been. We even discovered how creative you can be with bleach when the whole entire United States decided that they, too, wanted to tie dye their t-shirts all of a sudden!

We are knee-deep into “what if’s” and have been for quite some time. We all hoped that we would be at least close to the pandemic’s end. Our state, New Mexico has not allowed most students to return back to school. We managed to celebrate the milestones with drive- thru parades and virtual meetings with teachers at our schools. Virtual reality!!! It is real, and we have all witnessed it. Nothing is like it was!

The one positive that we all may share in these times - cherishing moments like the ones we had at After the Shock; Virtual Inhibitor Family Camp. Cherish being bored, as much as going out for a bike ride with your kiddos. Cherish watching that movie for the third time! Drive on a scenic road until your heart is content! Log off for a few hours to stop “liking” and “hearting” for once.... Log on with some friends on a video call for a few hours and really talk. Make the most of every connection that you can make. Cherish the memorable days, weeks and months because connections make times like these much smoother to move through.

Complimentary & Alternative Medicine - Uses in Bleeding Disorders PART 2

In the first installment, the definition of complementary and alternative therapy (CAM) was reviewed as well as the mind body modalities available. The second domain under review is the Manipulative and Body-based practices. “Manipulative and body-based practices encompass a system of therapies that use either manual manipulation or movement of one or more parts of the body to address structural or systematic imbalances of the bones and joints, the soft tissues, and the circulatory and lymphatic systems.”1

Massage involves the “rubbing and kneading of muscles and joints of the body with the hands, especially to relieve tension or pain.”2

There are no research studies that explore this modality with persons with bleeding disorders. A recent article published in Massage Magazine highlights recommendations made by a massage therapist when persons with bleeding disorders are considering massage for pain management. “A massage therapist needs to be especially careful with manipulating joints, as bleeding can easily occur at the major joint sites. Modalities which mobilize or stretch limbs may cause unnecessary stress upon joint structures. Friction strokes, which are classically ideal for addressing joints, need to be performed more cautiously. Deep tissue massage can carry the risk of increased bruising as well.”3 Based upon the available information, it is important to know your massage therapist and their ability to help. Use of this therapy should be reviewed with your treatment center, where the possibility of factor infusions prior to massage may be required.

Remembering Sarah Chan

By Barb Forss - LifeLines for Health Spring/Summer 2021 | Volume 17

Progress in the & Diagnosis Management of von Willebrand Disease

By Jonathan Roberts, MD - LifeLines for Health Spring/Summer 2021 | Volume 17

Emerging Advocates Could 'Sway' Copayment Accumulator Battle

By Gwen Cooper, Patient Services Incorporated, James Romano Care and Cure Partners- LifeLines for Health Spring/Summer 2021 | Volume 17

Complimentary & Alternative Medicine - Uses in Pain for Bleeding Disorders

By Angela Lambing MSN, ANP, GNP - LifeLines for Health Spring/Summer 2021 | Volume 17

Validation - Why You Need It. How To Ask For It. How To Give It.

By Dr. Gary McClain - LifeLines for Health Spring/Summer 2021 | Volume 17

Musculoskeletal Ultrasound Come to the LadyBugs Program

LifeLines for Health Spring/Summer 2021 | Volume 17