Genetic counseling for pre-implantation genetic testing of monogenic disorders (PGT-M)

Hematology: Heredity & Clotting FactorsTIME

TIME

December 27, 1963 12:00 AM GMT-5

All that most laymen know about hemophilia is that it is an odd and dangerous disease of the blood that strikes men only, although it is transmitted by women. Medical researchers have learned a great deal more than that, but when the nation's expert hematologists gathered in Washington, they realized that much more was still to be learned. They are baffled by at least eight bleeding disorders that are caused by the lack of any one of ten different clotting factors in the blood.

Genetic Lottery. Classical hemophilia, known since ancient times, is caused by a severe shortage of clotting Factor VIII. This disease, which afflicted a dozen descendants of Queen Victoria, results from a defect in a recessive gene carried on the x (female) chromosome. If a hemophilic man marries a normal woman, all their sons are normal but all their daughters are carriers. If a carrier woman marries a normal man (see diagram), each son has a fifty-fifty chance of being a victim and each daughter has a fifty-fifty chance of being a carrier. No one can predict whether a child will be affected, because a sort of genetic lottery decides which of the mother's chromosomes the child inherits. (How Victoria got the defective gene is a mystery. Medical sleuthing has failed to show that she inherited it, so she may have developed it herself—perhaps even from a direct hit on her ovaries by cosmic rays.†)

Classical hemophilia has now been renamed hemophilia A, because in 1952 a boy in England was found to be suffering from what had seemed to be the same disease, but his trouble was actually caused by lack of clotting Factor IX. This affliction is now called hemophilia B. It is transmitted the same way as hemophilia A, but the two diseases can be distinguished by the fact that blood from a hemophilia A victim, which contains Factor IX, will clot blood from a hemophilia B victim. A hemophilia B's blood, with its Factor VIII, will make an A's blood clot. Of an estimated 100,000 victims of clotting disorders in the U.S., 50,000 have hemophilia A and 15,000 have B.

Another bleeding disorder that is similar in its effects on patients, but totally different in inheritance and incidence is von Willebrand's disease. This is the most common of a group of clotting disorders that are transmitted by genes on some other chromosome than the x—which chromosome, remains a mystery. But it is a nonsex chromosome, so boys and girls are equally likely to inherit the defective gene.

No Direct Measure. "The trouble is," said the University of North Carolina's Dr. Kenneth M. Brinkhous, director of the U.S.'s leading hemophilia research program, "we can only measure the clotting factors indirectly by their effects—usually in the test tube."

But progress is advancing from the lab to the bedside. Factor VIII is now being extracted from human plasma and concentrated about 30 times. It is given by intravenous drip to victims of hemophilia A and von Willebrand's disease when they have crises of massive bleeding. Except in such emergencies, the usual treatment for all the clotting disorders remains a transfusion of fresh whole blood or plasma—not to replace blood that the patient has lost, but to supply the missing clotting factor and thus keep him from losing more.

Contrary to common belief, it is not outward bleeding from a wound that cripples and eventually kills most hemophiliacs; it is internal bleeding, especially into the joints, that does the damage. "This," said Manhattan's Dr. Henry H. Jordan, "is more crippling than either polio or arthritis. But it's incredible what rehabilitation can do. Many patients can discard a brace, for example, after five or even ten years." Today, some hemophiliacs work as longshoremen and loggers.

† She passed the gene to one son, two daughters: Leopold, who died at 31, was grandfather of Lord Trematon, who died at 21; Alice, who married Prince Louis of Hesse, had one hemophilic son who died at three, and two carrier daughters; Beatrice, who married Prince Henry of Battenberg, had two affected sons and a carrier daughter. Alice's elder carrier daughter Irene married Prince Henry of Prussia; one hemophilic son, Waldemar, lived to 56, but another died at four; Alice's younger carrier daughter Alexandra married Czar Nicholas II, was murdered with him and their hemophilic son, the Czarevitch Alexis. Beatrice's daughter Victoria Eugenie married Alfonso XIII of Spain, had two affected sons, Alfonso and Gonzalo, who bled to death after accidents.

Pfizer's Hympavzi Cuts Bleeding By 93% In Hemophilia A And B Patients With Inhibitors, Phase 3 Trial Finds

Out of the more than 800,000 people worldwide living with hemophilia, around 20% of those with hemophilia A and 3% with hemophilia B develop inhibitors, preventing their bodies from responding to standard clotting factor therapies.

Hympavzi (marstacimab) significantly reduced the annualized bleeding rate by 93% in young adults and older adults with hemophilia A or B with inhibitors, compared to standard on-demand, according to a phase 3 clinical trial.

Pfizer recently announced positive results from the BASIS study, the global phase 3 trial evaluating Hympavzi in young adults and adults with severe hemophilia A or moderately severe to severe hemophilia B who have developed inhibitors—or antibodies that block the effects of standard factor replacement therapy.

These inhibitors make traditional treatments ineffective, leaving patients with limited and often complex care options.

Out of the more than 800,000 people worldwide living with hemophilia, around 20% of those with hemophilia A and 3% with hemophilia B develop inhibitors, preventing their bodies from responding to standard clotting factor therapies.

This can lead to uncontrolled bleeding, increased hospitalizations and greater health risks, according to Pfizer.

The phase 3 trial—Basis—conducted by Pfizer, included 48 patients with hemophilia A or B and inhibitors.

According to the CDC, most people with hemophilia in the U.S. Are diagnosed at a very young age.

The median age at diagnosis is 36 months for those with mild hemophilia, 8 months for those with moderate hemophilia and 1 month for those with severe hemophilia.

Additionally, in about two-thirds of cases diagnosed as babies, there is a family history of hemophilia.

Hympavzi offers a new treatment option to address the challenges of the bleeding disorder.

Compared to traditional therapies that are used during bleeding episodes and replace the missing clotting factors (Factor VIII in hemophilia A or Factor IX in hemophilia B), Hympavzi works differently.

It targets a protein in the blood called tissue factor pathway inhibitor (TFPI) and then helps restore the natural balance between bleeding and clotting.

This process allows Hympavzi to remain effective even in patients with inhibitors to factor replacement therapies.

Administered through a once-weekly subcutaneous injection, Hympavzi is designed to be easy to use, requiring minimal preparation and eliminating the need for frequent intravenous infusions—a known barrier to adherence for many patients.

The BASIS study included 48 patients with hemophilia A or B and inhibitors.

Participants received Hympavzi prophylaxis over 12 months and were compared to their outcomes during a six-month period of on-demand treatment with intravenous bypassing agents—the current standard of care for people with inhibitors.

Hympavzi showed its success in all bleeding-related outcomes, including spontaneous bleeds, joint bleeds, target joint bleeds and total bleeds.

For example, the annualized bleeding rate (ABR) dropped from 19.78 with on-demand treatment to 1.39 with Hympavzi—a 93% reduction.

This was both statistically significant and clinically meaningful.

"Patients with inhibitors tend to face frequent complications, and navigating the treatment landscape can introduce complexities and increase disease burden," Davide Matino, M.D., BASIS principal investigator and associate professor of medicine at McMaster University, said in a news release. "The strong bleed reduction with Hympavzi compared to on-demand treatment in the phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options."

Hympavzi was generally well-tolerated in the study.

No deaths or blood clotting events were reported, and the safety profile was consistent with previous study phases and the non-inhibitor cohort of the BASIS trial.

Hympavzi was already approved in the U.S. In October 2024 for patients with hemophilia A or B without inhibitors, and it was the first anti-TFPI therapy to receive such approval. It is also approved in the European Union.

For eligible people with hemophilia B, it's also the first once-weekly subcutaneous prophylactic treatment available.

Pfizer is currently conducting additional studies, including the BASIS KIDS trial, which investigates the safety and efficacy of Hympavzi in children aged 1 to under 18 years.

Regulatory discussions are also underway to seek approval of Hympavzi for use in people with inhibitors.

As the space of hemophilia treatment continues to evolve, Hympavzi could cause a major shift—offering easier options, more consistent protection from bleeds and a new option for patients underserved by existing therapies.

World Hemophilia Day 2025 - April 17, 2025 - "Access For All: Women And ...

MONTREAL, April 17, 2025 /PRNewswire/ -- On April 17, 2025, the global bleeding disorders community will come together under the theme "Access for all: Women and girls bleed too" and celebrate World Hemophilia Day. Today, women and girls with bleeding disorders (WGBDs) are still underdiagnosed and underserved. The global bleeding disorders community has the power—and the responsibility—to change this. Through recognition, diagnosis, treatment, and care, the quality of life of WGBDS will improve, and the bleeding disorders community will become stronger.

World Hemophilia Day logo with name, April 17 and Recognizing all bleeding disorders

"Recognizing women and girls with bleeding disorders is a significant milestone for our community. In the past, they were often viewed solely as carriers rather than individuals with a bleeding disorder. It is time to fully embrace and acknowledge their experiences and struggles. Prioritizing the diagnosis and treatment of women and girls is crucial, and doing so strengthens our entire bleeding disorder community. Join us on April 17 to show your support for access for all—including women and girls."

—Cesar Garrido, WFH President

World Hemophilia Day 2025 is a call to action for governments, healthcare providers, and advocates worldwide to close the gaps in care for women and girls with bleeding disorders. These individuals often face delayed diagnoses, limited access to treatment, and a lack of understanding about their unique needs. By working together, we can challenge these inequities and ensure access to comprehensive care for everyone in the bleeding disorders community.

This year's theme highlights the importance of equity in healthcare, shining a light on the strength, resilience, and contributions of women and girls with bleeding disorders. Through global awareness efforts, we can break the stigma, improve education, and foster better outcomes for all.

World Hemophilia Day is an opportunity for individuals, organizations, and communities to come together and make a difference. Here are some ways to participate:

Get social by posting about inherited bleeding disorders and raising awareness on women and girls with bleeding disorders on Facebook, Twitter, LinkedIn and Instagram using the #WorldHemophiliaDay, #WHD2025, #WeBleedToo and #LightItUpRed hashtags

Support our global advocacy efforts and be a part of what we are building today for future generations by donating here

Share your story on the WFH story site about how your quality of life—or the quality of life of someone you know—has changed thanks to receiving a diagnosis, treatment and care on wfh.Org/whd

Contact your national hemophilia and bleeding disorders association to find out how you and other members can work together on World Hemophilia Day and raise awareness about women and girls with bleeding disorders

Download resources like posters and social media banners from wfh.Org/whd to help build your World Hemophilia Day Campaign

Send pictures, comments, or questions to the WFH at communications@wfh.Org

Story Continues

Let's join hands on April 17, 2025, to ensure that women and girls with bleeding disorders are not left behind. Together, we can create a future where Treatment For All is a reality, and equity, care, and empowerment define the lives of those living with bleeding disorders.

To learn more about World Hemophilia Day, please visit wfh.Org/world-hemophilia-day.

The WFH would like to thank our World Hemophilia Day sponsors for their continued support: Bayer, BioMarin Pharmaceutical Inc., Biotest, CSL Behring, F. Hoffman-La Roche Ltd., Grifols, Kedrion, LFB S.A, Novo Nordisk, Octapharma, Pfizer, Regeneron, Sanofi, Sobi, and Takeda.

About hemophilia and other bleeding disorders

In people with bleeding disorders, the blood clotting process doesn't work properly, with the result that they can bleed for longer than normal, and some people may experience spontaneous bleeding into joints, muscles, or other parts of their bodies which can lead to developmental and permanent mobility issues.

About the World Federation of Hemophilia

The World Federation of Hemophilia (WFH) is a non-profit organization dedicated to improving and sustaining care for people with inherited bleeding disorders around the world. At the WFH, national member organizations (NMOs) and health care professionals (HCPs) work together to provide care for people with inherited bleeding disorders around the world. We partner with governments and hemophilia treatment centres to enhance knowledge through training and provide tools they need to identify, support and treat people living with bleeding disorders in their communities, while promoting global advocacy and collaboration to achieve our common goals.

Our vision of Treatment for All is for a world where all people with inherited bleeding disorders have access to care, regardless of their type of bleeding disorder, gender, or where they live. Our mission is to improve and sustain care for people with inherited bleeding disorders around the world.

To find out more about the WFH, please visit www.Wfh.Org.

Media contact: Neha Suchak, Director, Marketing & Communications, nsuchak@wfh.Org, +1 514-875-7944, #2857, www.Wfh.Org

 

SOURCE World Federation of Hemophilia

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