Conflicts in medical management of hemophilia

AHF concentrates are a remarkable advancement in hemophilia treatment

By Everett Winslow Lovrien, M. D

Hemophilia is a medical disorder that is part of our genetic load as humans. It will never disappear. Therefore, the only way to live with it is to receive adequate medical management. Its effects on those males who have inherited the disorder that affects their blood clotting without treatment includes recurrent hemorrhages (bleeds) into joints as well as internal bleeding. The bleeds are painful, resulting in disuse, disability and crippling. The first signs usually appear in early childhood. A child who suffers a mouth bleed can slowly lose enough blood to result in death.

Prior to 1960, the expected life of a child born with severe hemophilia in the USA was less than 11 years. A common cause of death in childhood was bleeding into the brain, an intracerebral hemorrhage. This agonizing threat could be overcome with the discovery of Cryoprecipitate in 1964 by Dr. Judith Pool at Stanford University. The missing precursor to deficient clotting factor, antihemophilia factor VIII (AHF VIII) was obtained from the blood plasma of normal donors. A further step led to the production of AHF in the form of a lyophilized powder (Concentrates) that could be re-constituted and infused at home to treat bleeding. The introduction of concentrates was a marvelous innovative form of treatment that considerably improved the lives of those born with hemophilia by eliminating agonizing suffering.

Constraint in hemophilia treatment by HIV and hepatitis viruses

Despite the great success of Concentrate therapy for replacement of missing AHF in persons who have hemophilia, two conflicts have clouded the brightness of its use. The first major hazard of replacement therapy was the discovery that the magic medicine was contaminated with hepatitis viruses and HIV, the virus that cause AIDS. The drug companies that manufactured AHF Concentrates derived from plasma sacrificed safety bypassing purification in their drive for profitability. Thousands of boys and men who had hemophilia died all over the world from liver failure and AIDS as a result of the polluted medicine they infused to treat their bleeding episodes. More than 10,000 persons with hemophilia became HIV infected in the USA, which could have been prevented.

High costs limit availability of hemophilia treatment

The second conflict in AHF replacement is the cost of the medicine. AHF infusions to treat or prevent bleeds in hemophilia are not infused just once; instead infusions are required every few days in childhood. A person with severe hemophilia often exceeds 1,000 infusions by adulthood. The cost of treatment depends on the amount of AHF infused. A child requires less than an adult. A single treatment costs $1,000 to $2,000 for an adult. In the USA, estimates reveal that 12,000 persons with severe Type A hemophilia infuse an average of 171,760 units of AHF each year totaling 2,060,000,000 AHF units, including surgery. The average maintenance per person without surgery is less. However, recent recommendations for the prevention of bleeding in hemophilia include scheduled prophylactic infusions of Factor VIII, three times each week. A person who receives 150 infusions each year at 750 units per infusion will receive 112,500 AHF units; if the amount is 1,000 units three times each week, the yearly infusions total 150,000 units. The pharmaceutical manufacturing of AHF concentrates, as plasma derivatives and by genetic recombinant methods, world-wide is a multi-billion dollar industry. Production of AHF in 1995 equaled $2.4 billion, and amounted to $6 billion by 2011. AHF concentrates are sold primarily in countries with high incomes (RE: J.S. Stonebraker et al, Hemophilia (2010), 16, 33-46).

Hemophilia appears in males from all of the world’s races. With a world population of 7,000,000,000 (CIA, 2010) and an average birth rate of 20 per thousand individuals, there are 140,000,000 births each year in the world. One half are males, (70,000,000). One in 5,000 newborn males has hemophilia, equaling 14,000 new cases of hemophilia that are born in the world each year.

Within the U.S., with a population of 310,000,000, a birth rate of 14 per thousand equates to 4,340,000 births each year. In the U.S. 2,170,000 males are born annually. Experience has revealed that one in 5,000 will have hemophilia, equaling 434 new cases of hemophilia in the USA each year. Approximately 20,000 persons living in the USA have hemophilia ( RE: J.S. Stonebraker et al Hemophilia (2010), 16, 20-32). Of these, 12,000 are males who have severe type A hemophilia requiring Factor VIII replacement infusions.

Thanks to the federal government’s establishment of Hemophilia Treatment Centers, whose goal is to identify all of the persons who have hemophilia within the center’s health region, most cases of hemophilia in the USA, as well as in other high income countries are identified. Recognition is a necessary step that leads to treatment and relief from suffering.

But, that’s not the case in the major parts of the world. It is estimated that one–half, or even three-fourths of the children born in the world who suffer from hemophilia receive inadequate or no treatment (World Federation of Hemophilia, WFH). Often, they are not identified. The lack of treatment in economically poor counties of the world is the result of the high cost of the replacement AHF medicine, made in America without cost controls, that is not affordable in many countries.

Information provided by Mr. Patrick Robert of Marketing Research Bureau, Orange, Connecticut, for 2009 revealed the following:

The USA includes only 4.7% of the world’s population but it uses 30% of the Factor VIII concentrates produced in the world. 12,000 males (Type A hemophilia) using 2.06 billion units of AHF annually average 171,670 units for each person. This amount of AHF appears to be excessive but considering the large amounts of AHF utilized during surgery, prophylactic infusion therapy three times each week, and induction of immune tolerance to overcome inhibitors the amount may be even higher. Mr. Mark Skinner, president of WFH, believes the utilization of AHF will increase as children in the USA, who have been maintained on prophylaxis become adults. An adult male weighing 175 lbs who infuses 2,000 units of Factor VIII prophylactically three times each week uses 312,000 units each year, at a cost of $187,200 to $308,880 depending on whether recombinant or plasma-derived Factor VIII is infused.

Donations of AHF from pharmaceutical manufacturers to underserved person have been welcome. Pfizer has provided 10 million units of its ReFacto AHF to persons suffering from hemophilia in underserved countries, valued at $13 million (Medical.net/news 2010-02-03). Medical insurance providers may question the high prices of AHF Factor VIII they pay to pharmaceutical manufacturers for the benefits of their subscribers while they give away medicine to others without a cost. There remains a dilemma – a marvelous treatment exists but it is not affordable for most persons in the world. AHF treatment is available for persons who live in rich countries—so, a societal issue arises. If medicine exists to provide treatment, relieve pain and suffering, prevent disability and prolong life expectancy, is it a basic human right that the medicine should be available to everyone who needs it?

WFH and the National Hemophilia Foundation (NHF) continue their advocacy for all persons born with hemophilia. The Hemophilia Treatment Centers (HTC) in the USA have improved the management of hemophilia resulting in an improved quality of life and increased life expectancy within the USA. Other countries that have a high average income have also experienced the improvement of hemophilia care as the result of the pharmaceutical manufacturers’ entrepreneurship. The innovative production of AHF for the treatment of hemophilia as a safe plasma derivative and by genetic recombinant methods by industry has been remarkable. The challenge ahead for treating hemophilia has shifted from production of medicine to distribution.