Monthly Archives: March 2011

Hemophilia 101: What is it, and How is it Treated?

What is Hemophilia?

Persons affected by hemophilia have a disturbance in their blood coagulation. Blood circulates many many times in its endless course through a person’s blood vessels without leaking. Damage to a blood vessel may result from a noticeable injury such as a twisted ankle, or even an unnoticeable event such as bumping into the corner of a table.

Bleeding episodes in hemophilia are recurrent, as often as every three or four days, with many persons experiencing more than 1,000 hemorrhages during childhood and adulthood.

When a blood vessel is damaged, allowing blood to escape, a person’s body reacts in three different ways:

  1. First, adrenalin is released by the presence of injured tissue producing vasoconstriction (that restricts the flow of blood in the injured blood vessel).
  2. Secondly, platelets from the blood stream are attracted to the site of injury in the blood vessel wall. The platelets form a plug to stop the bleeding.
  3. Thirdly, fibrin is laid down in the platelet plug to give it strength and allow the plug to retract promoting healing to take place. In a person who has hemophilia, the third step–fibrin cementing of the platelet plug–is deficient. As a result, the platelet plug that forms does not solidify; it is mushy. Oozing of blood continues sometimes for days that may be visible as a bruise or a painful hemorrhage referred to as a bleed by persons who have hemophilia.

Fibrin does not circulate normally in blood. If it was always present, an undesirable blood clot might form resulting in a stroke or heart attack.   Fibrin requires activation from its precursor, fibrinogen, by another blood protein, thrombin. And thrombin must be activated from its precursor, prothrombin. Two of the proteins that activate prothrombin are Factor VIII and Factor IX.  In the most common type of hemophilia, Hemophilia A, Factor VIII is deficient. In persons who have Hemophilia B, Factor IX is deficient.  The antihemophilia factors , AHF, activate prothrombin to form thrombin that activates fibrinogen to fibrin during blood coagulation to form a firm platelet plug while healing takes place in the injured blood vessel wall.

Persons who have Hemophilia A and Hemophilia B have a mutation in their Factor VIII or Factor IX gene. Both genes are on the X chromosome. Several different mutations in both genes have been described.  Although multiple molecular defects have been discovered, they all have nearly the same medical effect.  The most common hemophilia mutation, intron 22 inversion, accounts for one-half of Factor VIII deficiency.

Hemophilia Facts:

  • In the USA, approximately 400 babies are born each year that have hemophilia with a frequency at birth of 1 in 7,500 newborn males.
  • One-third of newborn babies with hemophilia are the first instances in their family. However, the mothers of such infants may be carriers of hemophilia by receiving mutant sperms from their non-hemophilic fathers when they were conceived.
  • Hemophilia nearly always occurs in males and is present in all countries and ethnic groups.  Males who marry and have children will transmit their mutant hemophilia gene to all of their daughters and none of their sons.

Hemophilia Treatment

Prior to 1960, life expectancy for a person born with hemophilia in the USA was eleven years.

The most common life threatening hemorrhage was an intracerebral bleed. Those who survived severe hemophilia suffered and were disabled from recurrent joint bleeds. During childhood, recurrent bleeding episodes were sometimes as frequent as several times each week. With advances in Factor VIII  and Factor IX AHF replacement treatment, painful suffering and life threatening hemorrhages in hemophilia have been greatly diminished.

Following the turmoil in hemophilia treatment caused by HIV infection and death from AIDS,  improved AHF from plasma-derived Factor VIII and recombinant Factor VIII and Factor IX is restoring life expectancy toward normal and minimizing agony and suffering from recurrent hemorrhages in countries of high income where a method of payment for AHF exists.  With replacement AHF, persons with hemophilia are able to attend school without bleeds interfering with their attendance, attain dental care, and even withstand surgery.  They can become productive adults with the security of employment. Marriage and having a family are attainable.

Hemophilia will never disappear.  There will always be new mutations as part of human nature. But there may be a cure someday, more than just treatment, with the further refinement of gene transfer.  Hemophilia will probably be one of the first genetic disorders to be cured with gene transfer.

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Cost of Treatment: An Obstacle to Hemophilia Care

A second hurdle has appeared in the path to treatment of hemophilia.  After the introduction of commercially available Antihemophilia Factor for treating hemophilia with Factor VIII and Factor IX in the early 1970s, life completely changed for those boys and men who suffered pain and agony, becoming disabled ending with a short life expectancy prior to the new AHF concentrates. For 10 years life for persons with hemophilia was sailing along almost equal in quality to a person without hemophilia.

The first hurdle that interrupted the treatment was the contamination of the new medicine with HIV and hepatitis viruses.  Many persons died of AIDS or liver failure as the result of the viruses in the medicine. By 2008, in person with hemophilia, 13,083 developed AIDS.   Those days are past as the result of the entrepreneurship of the pharmaceutical manufacturers who have  produced safe medicines utilizing advanced methods  including genetic engineering resulting in a recombinant AHF.  Plasma derived AHF has been deviralized and made safe.

The second hurdle in the path of treatment for hemophilia is cost.  The comprehensive study of Factor VIII use around the world by Stonebraker and colleagues ( 2010) revealed that medicine to treat hemophilia is used primarily in countries with high incomes. One-half or more of the hemophilia persons in the world receive inadequate or no treatment. Most low income countries have other conditions that receive a higher priority such as infectious disease, malaria, violence, natural disasters and inadequate economic development.

The population of the United States, 310 million compared to the world population,  7 billion, is only 4.7%. The annual world production of Factor VIII totals 6.9 billion units (2008). However 12,000 persons in the USA use 2.06 billion units amounting to 30% of the world production. The infusion of Factor VIII per person in the USA averages 171,670 units annually. When recombinant Factor VIII is used at $.90 -$.95 per unit the cost per person annually equals or exceeds $150,000.

Selling Factor VIII in the USA is possible despite the high costs because there is a way to pay for it.  In countries of low income, no method of payment exists.  Should there be a needed medicine that is available but not affordable?  The United States is a country of high consumerism. But it is also a country of high pollution. As a result of the contribution to global warming and pollution of the ocean with plastic debris by the USA, an economic effect has been felt in poor countries as their fishing has declined.  Citizens have been deprived of an income and cannot pay taxes.  There is no way to buy expensive medicines.

A solution might include transferring the modern technological methods of Factor VIII production to countries of low incomes while retaining domestic production of the medicine for use in the U.S.A.  The U.S.A. has an obligation to assist in the world economics. There are cars in the world and they cannot all be made in America. Similarly, the world’s production of Factor VIII cannot all be made in America. The production of Factor VIII by U.S. pharmaceutical manufacturers of medicine to treat hemophilia would not be threatened by assisting low income countries to produce their own medicine, for presently there are almost no sales of medicine to the countries of low income. The establishment of facilities to produce the medicine in other counties must be completed by the pharmaceutical industry, not the federal government.

Just as Nike makes shoes in Malaysia, Wyeth, Pfizer etc could make Factor VIII in Pakistan or Somalia. The drug companies would monitor and supervise and assist in production. Rather than selling poor countries AHF medicine, let’s show them how to make their own.  Such an action would create employment, relieve suffering and contribute to a better world.

-Everett Winslow Lovrien, M.D.

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St. Patrick’s Day: 3 Things We are Lucky to Have as Americans

  1. Let's hope for some luck of the Irish!

    HTC: We are Lucky because the federal  government in the USA successfully demanded that all persons in the USA who have hemophilia should be identified followed by a heath care plan for each individual. The first step in establishing good medical care is the identification of those who need it. In 1976 The Children’s Bureau of Health and Human Services  established and funded the Hemophilia Treatment Centers (HTC) in each of the ten Health Region of the country. Before then, many patients in the USA were not identified and did not receive adequate care.

  1. AHF:  We are lucky in the U.S. because we have a pharmaceutical industry where innovation in the development of medicines flourishes.  Research and development of AHF clotting Factors has resulted in the production of safe plasma-derived AHF and recombinant AHF for both Factor VIII and Factor IX types of hemophilia. The availability of replacement AHF therapy has increased life expectancy. Improvement in the quality of life for persons who have hemophilia includes dental and surgical procedures, regular attendance at school, ability to maintain employment, marriage, raising and supporting a family.
  1. Source of AHF: We are lucky to have a system of distribution and availability of AHF.  A medicine that is not available or that is unaffordable is useless.  A responsibility of the HTC is to recognize the need of AHF for hemophilia patients and to identify a method of payment for the cost of the medicine.  For each patient a reliable source of AHF is identified. No person who has hemophilia should lack medicine because of the cost of the medicine.   The availability of replacement AHF for infusions at home allows a patient to assume independence and responsibility accompanied by freedom and control of their lives.

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‘Doctor Guilt?’ Excerpt: Home Infusion Therapy

This excerpt is from Doctor Guilt?, pg. 250. These remarks are from Dick Wagner:

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