Treating Hemophilia

THE NEED TO MAKE TREATMENTS SAFE Treating Hemophilia 

In the early 1980s, the development of HIV/AIDS in young blood transfusion patients was a powerful incentive to find other sources for the blood-derived proteins used to treat hemophilia, a group of inherited disorders affecting the clotting of blood. Hemophilia has 

Hemophiliacs are treated with clotting factors when they have severe bleeding episodes, and are also treated to prevent bleeding if surgery or any other activity that might lead to bleeding is planned. Before recombinant technology, the fluid part of normal human 

Something had to be done to protect hemophiliacs from serious bleeding problems without infecting them with a deadly virus. 

Better methods for preparing clotting factors from blood and the development of recombinant clotting factors provided the solutions. Methods of detecting, inactivating, and removing viruses were improved, and none of the hemophilia replacement products— conventional or recombinant—has transmitted either HIV or hepatitis since 1987. As an alternative, recombinant clotting factors 8 and 9, produced in animal cells, were approved in 1992 and 1997, without the risk associated with human blood products. 

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Natural source may carry risk of infection. Recombinant Factor VIII used to treat hemophilia A has helped reduce the incidence of HIV infection in hemophiliacs. Recombinant HbsAg is now used to immunize against hepatitis B, eliminating the risk of introducing a viral infection during vaccination. 

A newer generation of retroviral vectors, based on the lentivirus, hold the same advantages of retroviral vectors with the added ability to transduce non-dividing cells efficiently. Pre-clinical studies with lentiviral vectors for the treatment of hemophilia have shown great promise. Using a feline immunodeficiency virus (FlV)-based vector, Stein et al. showed that 9 of 12 treated hemophilia A mice could express greater than 5 ng/ml factor VIII, six of which... 

High, K. A. (2003). Gene transfer as an approach to treating hemophilia. Semin. Thromb. Hemost. 29, 107-120. 

In the past, hemophiliacs were treated with transfusions of a concentrated plasma fraction containing factor VIII. This therapy carried the risk of infection. Indeed, many hemophiliacs contracted hepatitis and AIDS. A safer preparation of factor VIII was urgently needed. With the use of biochemical purification and recombinant DNA techniques, the gene for factor VIII was isolated and expressed in cells grown in culture. Recombinant factor VIII purified from these cells has largely replaced plasma concentrates in treating hemophilia. 

United Kingdom Hemophilia Centre Doctors Organisation (UKHCDO). Guidelines on the selection and use of therapeutic products to treat hemophilia and other hereditary bleeding disorders. Hemophilia 2003 9 1-23. 

B. Clotting Factors The most important agents used to treat hemophilia are fresh plasma and purified human blood clotting factors, especially factor VIII and factor IX, that are either purified from blood products or produced by recombinant DNA technology. These products are extremely expensive and carry a risk of infection (due to contamination by blood-home pathogens) and immunologic reactions. 

Vitamin K has proved ineffective in treating hemophilia, an inherited condition causing abnormal hemorrhaging in man. 

O Intravenous factor replacement with recombinant or plasma-derived products to treat or prevent bleeding is the primary treatment hemophilia. Primary prophylaxis is defined as the regular administration of factor concentrates with the intention of preventing joint bleeds.4 The rationale for primary prophylaxis is that individuals with factor levels of greater than 0.02 unit/mL (2 IU/dL) rarely suffer from spontaneous bleeds and arthropathy. Therefore, to maintain a trough level above this might convert severe hemophilia to moderate disease, with the abolition of joint bleeds and the associated arthropathy.5... 

Antihemophilic factor Antihemophilic factor is a protein that converts prothrombin to thrombin, and replaces a deficit of endogenic hemophilic factor. It is synthesized by processing human plasma [69-70]. It is used to treat classic hemophilia A and to stop bleeding. Synonyms of this drug are hemophil T, monoclate, cryoblin, and others. 

Along with the primary use of this drug as an antidiuretic for treating diabetes, it is used to treat classic hemophilia A. A synonym of this drug is DDAVP. 

Hemophilia There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional Factor VIII was required. 

Desmopressin is sometimes used in mild Hemophilia A and Von Willebrand s disease. In December 2007, US drug regulators banned using desmopressin nasal sprays for treating bedwetting after two children died from hyponatremia. 

The antiplatelet action of aspirin contraindicates its use by patients with hemophilia. Although previously not recommended during pregnancy, aspirin may be valuable in treating preeclampsia-edampsia. 

There have been several reports of seizures in association with hyponatremia after intravenous administration of desmopressin to cover surgery in young children with congenital bleeding disorders such as mild hemophilia A or von Willebrand s disease (58-60). Hyponatremia and convulsions have occurred in children without congenital bleeding disorders who received desmopressin for urine concentration tests or to treat nocturnal enuresis (54,61,62). 

Bond L, Bevan D. Myocardial infarction in a patient with hemophilia treated with DDAVP. N Engl J Med 1988 318(2) 121. 

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