Bleeding Disorders Historical Timeline

The first European with a bleeding disorder is believed to have arrived in the American colonies.

Isaac Zoll dies at age 19 from a minor cut on his foot. He is regarded as the first American with hemophilia.

Hemophilia is first named.

Queen Victoria ruled the United Kingdom from 1837 until her death in 1901. She is origin of hemophilia in the royal families.

The book Domestic Medicine is published. It includes treatments for hemorrhages and internal bleeding.

People with bleeding disorders struggled with frequent injuries and bleeding. The average life expectancy was age 14 for people with moderate to severe hemophilia.

Von Willebrand Disease is first described.

The life expectancy for someone with severe hemophilia is only 20 years old. Advances in transfusion medicine improve life expectancy.

Treatment is limited to whole blood transfusions, bed rest, leg braces, and compression.

The National Hemophilia Foundation is founded by Betty Jane and Bob Henry, parents of a son with hemophilia.

The US Army shows that soldiers using pooled plasma have a higher incidence of jaundice.

Since treatment is limited to whole blood, researchers seek alternative means to prevent and treating bleeding episodes.

Mary M. Gooley, RN assembles one of the first comprehensive care centers in Rochester, NY.

This era marks a time of research into effective treatment for hemophilia as whole blood continues to be the only effective treatment.

Hemophilia is referred to as “the disease of kings” and the “bleeder’s disease.”

The World Federation of Hemophilia is founded.

Dr. Judith Graham Pool discovers cryoprecipitate. This is the first successful treatment for hemophilia beyond whole blood.

After cryoprecipitate is developed, life expectancy grows to 24 years old.

Researchers Dr. Edward Shanbrom and Dr. Murray Thelin (who had hemophilia) begin work on developing a clotting factor concentrate.

Clotting factor is given to a hemophilia patient for the first time at Hyland Labs in Glendale, CA.

As factor concentrate becomes available, patients are given instructions on how to access it. Availability of factor concentrate varies by center and region.

Women, people of color, and those living in rural areas are rarely mentioned in the media.

The National Hemophilia Foundation uses young boys to serve as the face of hemophilia and use taglines like ‘Help Him Walk On His Own.’

Dr. Shelby Dietrich leads Orthopedic Hospital in Los Angeles, California in becoming a well-respected center for hemophilia care.

Camp Bold Eagle in Michigan becomes the first hemophilia summer camp in the country for children with bleeding disorders. Camp gives children the opportunity to be around others like themselves, and for many this is the first time they meet others with hemophilia.

Despite medical advancements, many patients with hemophilia have joint damage from years prior. The community rallies support to help these patients receive appropriate care.

Factor concentrate usage continues to vary. Some doctors are still prescribing and instructing patients to use cryoprecipitate in the early 1970’s. Treatment at home is becoming more prevalent and patients no longer feel tethered to the hospital.

For many years, hemophilia families are responsible for organizing blood drives to replace the donations needed for transfusions. There remain common as cryoprecipitate and clotting factor become more widely available.

Celebrities join the cause to help promote blood drives.

Researchers identify a new method for identifying carriers of the hemophilia gene.

The Hemophilia Act passes, launching the formation of a nationwide network of federally funded hemophilia treatment centers.

Hepatitis non-A, and non- B, later known as Hepatitis C is a growing concern due to pooled blood being used in treatment. However, it is deemed an “acceptable risk” since clotting factor extends patient life expectancy.

Hemophilia affects many generations within one family. The media continues to draw attention to the plight of those living with the condition. Even with advances in treatment, factors such as race, ethnicity, gender, socio-economic status, and location created barriers to treatment.

An article in The Journal of the American Medical Association notes it is possible to heat treat albumin, a blood product, to effectively kill some of the hepatitis viruses. While this process was industry standard in Germany, another major producer of antihemophilic factor concentrates, it did not become mainstream in the U.S. until the mid-1980’s.

Those living with hemophilia now enjoy an improved quality of life.

Clotting factor was made by pooling blood of up to 10,000 donors. If one donor was infected with a viral pathogen, the entire batch was infected. In 1982, the CDC reported the first cases of HIV/AIDS among people with hemophilia, and by mid-1983, researchers were able to isolate the virus that causes AIDS. Manufacturers of plasma derived clotting factor concentrates attempted to kill these viruses with dry heat, solvent detergent treatment, and pasteurization with varying degrees of success. Manufacturers licensed and began developing heat- treated products, but these were not widely available due to high cost, perceived risk, and questions over efficacy. Many in the hemophilia community became isolated due to discrimination and fear of being identified as HIV/AIDS positive. Children, most notably Ryan White and the Ray brothers, were denied entry to school. By the late 1980s, over 50% of the hemophilia community had been infected with HIV/AIDS and/or Hepatitis C. In those with severe hemophilia, the infection rate was over 90%. The decades-old concern over hepatitis was now far overshadowed by the HIV/AIDS epidemic

The CDC reports an unknown pneumonia amongst 5 young men in Los Angeles.

The CDC releases a MMWR detailing a rare pneumonia amongst 3 hemophiliacs. In light of this new information, a meeting was held nine days later on July 27. At this meeting which included representatives from FDA, CDC, Public Health Service, NIH, American Blood Resources Association, and NHF, the decision is made to change the condition’s name from Gay Related Immune Deficiency (GRID) to Acquired Immune Deficiency Syndrome (AIDS).

An infant who had received a transfusion dies of an ‘immune deficiency illness. In the MMWR report outlining the infant’s death, the CDC also reports first AIDS cases among people with hemophilia and expresses concern “about the possible transmission of AIDS through blood and blood products.”

The CDC hosts a meeting to address the growing concern over the safety of the nation’s blood supply. At the conclusion of the meeting no recommendations or changes are made.

The CDC issues another MMWR stating that AIDS was being transmitted through infected blood and blood products, placing the entire hemophilia community at risk of infection. The CDC recommends steps to be taken immediately to keep the blood supply safe.

HHS begins approving licensing for heat-treatment of clotting factor. Several US manufacturers begin the development of heat-treated factor concentrate after testing shows the process kills both the HIV and hepatitis viruses.

The National Hemophilia Foundation sends notices to individuals and local chapters urging patients to continue the use of clotting factor, despite warnings from the CDC that the blood supply is tainted with HIV/AIDS.

Manufacturers begin issuing clotting factor recalls.

Based on a report from The Annals of Internal Medicine, transfusion-associated HIV/AIDS is proven to be sexually transmittable. Community members begin to consider how their HIV/AIDS status would impact their close relationships.

The first diagnostic test for the retrovirus that causes HIV is developed. The number of people with hemophilia diagnosed with HIV/AIDS is growing rapidly.

The CDC reports an alarmingly high number of factor concentrates contained HIV/AIDS.

Letters from the National Hemophilia Foundation continue to reaffirm the recommendation that patients use clotting factor even as product recalls are issued.

In the midst of fear and confusion, Ryan White and his family from Indiana emerge as spokespersons for those living with hemophilia and HIV/AIDS, especially after Ryan is denied entry to his school.

FDA stops issuing licenses for non- heated-treated clotting factor, however, the decision is left up to manufacturers on how to handle their inventory. It is 1991 before FDA issues a mandatory recall and destruction of non-heated- treated clotting factor.

Like Ryan White, three hemophiliac brothers are denied entry to their Florida school. The Ray brothers take their case to court and are awarded the right to return to school. Shortly after the decision, their home mysteriously burns to the ground. The media coverage following the fire is often considered a significant event in the history of HIV/AIDS in the United States.

The first product for the treatment of von Willebrand Disease becomes commercially available.

During this period, many in the hemophilia community feel they are not getting the answers they seek. The Committee of Ten Thousand (COTT) and Hemophilia-HIV/PEER Association are formed to demand more information and transparency for those who contracted HIV/AIDS from tainted blood product.

The first World Hemophilia Day is observed on April 17 to increase awareness of hemophilia and other bleeding disorders. April 17 is chosen in honor of Frank Schnabel, the founder of the WFH.

The 1990s were a period of action in the hemophilia community. National grassroots associations like the Hemophilia-HIV Peer Association, Committee of Ten Thousand (COTT), and Hemophilia Federation of America (HFA) formed to address the unheard needs of the community. During this time, information about HIV/AIDS was not readily available; information could be found in the gay community and was emerging in the hemophilia community, but questions still lingered. Litigation against the drug manufacturers dominated most of the 1990’s. Some patients filed individual cases, while others were part of large class settlements. Other chose not to pursue a settlement. After the 1995 release of the Institute of Medicine’s report, “HIV and the Blood Supply,” a grassroots legislative effort developed, culminating in the passage of the Ricky Ray Hemophilia Relief Fund Act of 1998.

Ryan White dies at the age of 18.

Dr. Dana Kuhn amasses 350 documents detailing the sequence of events on how inadequate decision making led to the widespread infection of HIV/ AIDS among the hemophilia patient community.

The hemophilia patient community begins to independently ask their own questions and galvanize. Local and national hemophilia organizations and others seek answers to why they were given misinformation and to hold accountable those who failed to prevent the spread of HIV/AIDS to people with hemophilia.

Blood screening for Hepatitis C becomes available.

Ricky Ray, one of three brothers infected with HIV/AIDS, dies at age 15.

The first recombinant factor VIII concentrate becomes commercially available. It is 1997 before a recombinant IX concentrate becomes commercially available.

Litigation against drug manufacturers dominates most of the 1990’s. Some patients file individual cases, while others are part of large class action suits. Others choose not to pursue a settlement.

Hemophilia Federation of America forms as a sub-group of COTT in 1993 and becomes independent in 1994.

HFA bridges the gap between the advocacy efforts COTT is working on, and is a place of education, advocacy, and awareness for families living with bleeding disorders. HFA continues today to serve as a voice of the community.

The divide in the community rests between those who were co-infected and newly diagnosed families. Many of the HIV/AIDS infected seek compensation due to the mounting medical debt and demand accountability from the government and manufacturers. Newly diagnosed families worry that the lawsuits could potentially keep them from accessing newer, safer clotting factor.

Following a request from the Department of Health and Human Services, a Committee of the Institutes of Medicine (IOM) reviews the scientific evidence that was available to decision makers during the early 1980’s when the HIV/AIDS epidemic first emerged. The IOM releases a report called, HIV and the Blood Supply: An Analysis of Crisis Decision Making, which outlines several recommendations in making the blood supply safer and gives a list of action items including the need for consumer representation on governmental blood advisory groups.

A critical question in the litigation is why heat treatment was not perfected until 1983 for clotting factor. Heat treated clotting factor was shown to effectively eliminate the transmission of HIV/AIDS and some hepatitis viruses.

The financial burden of lost loved ones is felt by their families.

While other countries are finalizing settlements by 1996, negotiations in the US continue due to years of stalled litigation.

The negotiations of the settlement bring up painful questions for patients and families.

After the IOM report and many attempts at class action suits, victims and their families gain traction in holding the pharmaceutical companies accountable for infected clotting factor products.

Frequent updates and information to the community are being sent regarding the status of the Ricky Ray Hemophilia Relief Fund Act.

As a result of the community’s tireless grassroots efforts, Congress begins to show support for those affected.

After tireless efforts, President Clinton signs the Ricky Ray Hemophilia Relief Fund Act of 1998 on November 12, 1998.

The hemophilia community between the HIV/AIDS-era families, and post- heat treated, and recombinant factor using families slowly began to heal. The financial burden of living with hemophilia was felt in lifetime caps and out-of-pocket expenses. In 2007, the Joint Outcome Study was released showing that prophylactic treatment is favorable to on-demand treatment in reducing joint and life-threatening bleeding. Much attention is devoted to the development and treatment of inhibitors in hemophilia.

The hemophilia community sees a resurgence in families coming together through camps, local, and national meetings. The term, “hemophilia” begins to be replaced by the term “bleeding disorders” to acknowledge all bleeding conditions. Treatment costs continue to rank among the most expensive chronic conditions. The financial impact continues to burden families.

Recombinant Factor VIII product shortages instill concern about the supply of necessary clotting factor concentrates.

Attention is now given to other rare bleeding disorders, the newly diagnosed, women, people of color, and those living in rural areas.

Although about 30% of Hemophilia A and 2-3% of Hemophilia B patients will form an inhibitor and have been of concern since clotting factor was discovered in the 1960’s, resources and education about this complication had been scarce. Education and outreach increase for inhibitor families in the mid- 2000’s.

Dr. Marilyn Manco-Johnson et al., publish a multi-year study showing a prophylactic regimen of treatment prevents joint damage in pediatric patients in the New England Journal of Medicine.

Lifetime caps are continuing but growing concern in the hemophilia community, especially for inhibitor patients. This issue will later inform decisions around the Affordable Care Act.

President George W. Bush signs into law the Genetic Information Nondiscrimination Act (GINA) to protect Americans against discrimination based on their genetic information when it comes to health insurance and employment.

A product for those with Factor I deficiency becomes commercially available.

The passage of the Affordable Care Act in 2010 assures those living with bleeding disorders cannot be denied for pre- existing conditions and that most plans eliminate lifetime cap issues. Increased research and awareness is conducted for women with bleeding disorders and von Willebrand disease. Future treatment includes the development of new clotting medications and gene therapy. Quality of life has dramatically improved for most living with hemophilia and life expectancy is nearly the same as most healthy people.

The Affordable Care Act (ACA) passes and is signed into law by President Barack Obama. The ACA addresses lifetime caps, pre-existing conditions, out-of-pocket expenses, young adult coverage, and other needs important to people with bleeding disorders.

A product for Factor XIII deficiency becomes commercially available.

Hepatitis C continues to devastate the bleeding disorders community and is the leading cause of death in adults with hemophilia. This is the defining issue for the adult bleeding disorders population; available treatments are difficult and often not effective.

The National Hemophilia Foundation in partnership with others launches My Life, Our Future, a project to genotype hemophilia patients and carriers.

Continued improvements in and expansion of research, education, and conversation about von Willebrand Disease and women with bleeding disorders occurs.

After years of continued struggle with Hepatitis C, a new product becomes commercially available. Hepatitis C is no longer the leading cause of death in adult hemophiliacs in the US. The new product is hailed as a cure for Hepatitis C.

Extended half-life clotting factor VII and IX concentrates become commercially available.

The first recombinant product for von Willebrand Disease becomes commercially available.

The first Factor X product becomes commercially available.

After 32 years of an FDA ban on blood donations from men who have sex with men (MSM), the FDA reconsiders and votes to continue the ban with a deferment period for MSM or their female partners for one year after last sexual contact.

Opioid dependency increasingly becomes a topic of concern for the bleeding disorders community.

With a new Administration in place, Congress makes multiple attempts to dismantle the Affordable Care Act. In a floor speech, Senator Bernie Sanders asserts that the hemophilia community would be disproportionally impacted. These efforts fail and the ACA is left intact.

The National AIDS Memorial Grove unveils a dedicated area and memorial for the hemophilia community.

A subcutaneous, bi-specific antibody therapy becomes commercially available to those with hemophilia A and inhibitors. This product gets approval for hemophilia A patients a year later.