Clinical Aspects of and Therapy for Hemophilia B. Harold R. Roberts and T, Flint Gray III, страница 6

Major Bleeding

Major bleeding episodes (i.e., those involving the gastrointestinal tract or central nervous system, or life-threatening bleeding in or around the airway or retroperitoneal space) should be treated with factor IX in doses sufficient to achieve levels of E50% of normal; usually higher levels are indicated. Levels of 100% can be achieved using the pure factor IX preparations with minimal risk of thrombosis. Treatment should be continued for F7–10 days, or until the bleeding episode is controlled and resolution of the hematoma begins. Therapeutic recommendations are summarized in Table 108-3 Table 108-3.

Monitoring Therapy

Factor IX therapy lasting <1 or 2 days or given for a hemarthrosis need not be monitored by factor IX assays as long as the patient does not have an inhibitor and is known to respond to conventional doses of factor IX. When factor IX is administered for serious bleeding, assays for factor IX immediately after the initial dose and on a daily basis thereafter are indicated to maintain peak levels of 50–100% and minimum levels of 25–50%. Replacement therapy with crude factor IX concentrates for >5–7 days should be monitored carefully in light of the potential for thrombotic complications.


Viral Hepatitis and HIV Infection

The success of treatment of hemophilia with clotting factor concentrates has been tempered first by the transmission of viral hepatitis and, more recently, by HIV transmission.

Most patients who received factor IX concentrates before 1984 show evidence of hepatitis B infection. 38 Many of these patients have chronic hepatitis, and a proportion have developed cirrhosis, which can be of particular concern in the hemophilic population due to the risk of bleeding from varices. Hepatitis C, which accounts for most non-A, non-B hepatitis, is now thought to be the major cause of chronic liver disease in these patients. Efforts to decrease the risk of hepatitis in donated blood began with screening for hepatitis B surface antigen in 1972. Before the recent introduction of a test for hepatitis C antibody, elevated alanine aminotransferase and hepatitis B core antibody were used as surrogate markers of hepatitis C infection. The use of the hepatitis C virus antibody test should further decrease the risk of contamination of plasma-derived products with hepatitis C virus.

In addition to screening of the blood supply, the availability of the hepatitis B vaccine since the 1980s has allowed further means to decrease the risk of hepatitis B infection. All hemophilic patients not previously infected with hepatitis B should be vaccinated. Hepatitis C vaccines are not presently available.

The problem of hepatitis infection led to the addition of viral inactivation steps to the manufacture of clotting factor concentrates beginning in 1983. The methods used include dry heating, heating in solution or in solvent-suspension, treatment with solvent/detergents, and immunoaffinity chromatography and ultrafiltration. MLID93206146  39

In retrospective studies, HIV seropositivity was detected in blood samples from multitransfused hemophilic patients from as early as 1978. AIDS was first reported in hemophilic patients in 1982, but most seroconversions probably occurred between 1981 and 1983. MLID86131971  40 AIDS has now exceeded hemorrhagic complications as the most common cause of death in the hemophilic population. HIV infection rates have been significantly lower for patients treated with factor IX concentrates (30–50%) compared with those treated with factor VIII concentrates (70–90%), probably due to the additional steps in manufacture of factor IX concentrates. MLID93206147  38,42 Fortunately, all current clotting factor concentrates appear to be safe in terms of transmission of viral disease. However, because clotting factor concentrates are prepared from pooled human plasma from as many as 20,000–30,000 donors, the possibility exists for contamination with new pathogenic viruses resistant to current inactivation practices. There is also a remote possibility of breakdown in the manufacturing process that could result in viral contamination of clotting factor preparations. The development of recombinant methods for production of factor IX may decrease the risk of these potential problems. MLID93206147  42

Disseminated Intravascular Coagulation and Thromboembolism