HCV has been a common infectious complication of factor infusion. (It was termed non-A, non-B hepatitis in the 1970s. MLID77202197 52) A serologic marker for HCV is available. MLID89222454 MLID89222455 53,54 Data suggest that E80% of persons with hemophilia infused before 1985 carry the marker, indicating past exposure to the virus. Approximately 90% of hemophiliacs have either persistently or intermittently elevated liver enzymes, which most likely represents the consequences of HCV exposure. 55 When liver biopsies are done on selected hemophilia patients with abnormal liver enzymes, 20%–30% have shown changes consistent with chronic active hepatitis or cirrhosis. MLID85253208 56 HCV has also been associated with the development of heptacellular carcinoma. MLID91314600 57 Thus, HCV may represent a long-term problem for persons with hemophilia.
Outbreaks of hepatitis A related to factor concentrate have recently been reported from Europe. As a vaccine for hepatitis A becomes available, newly diagnosed persons with hemophilia should receive it.
Human Immunodeficiency Virus
HIV was introduced into the American blood supply in the 1970s. 58 By the late 1970s, factor concentrate was widely contaminated and by 1982, approximately 50% of persons with hemophilia were infected with HIV. 59 Currently, 70% of American hemophiliacs are HIV antibody positive. 60 Hemophilic patients, especially those infected after the age of 22 years and those who have been HIV seropositive for at least 7 years, have approximately 40% probability of developing symptomatic AIDS. MLID87239713 61 It is not clear why the age of acquisition of infection should influence outcome, but this has now been confirmed in a larger multicenter study. MLID90015005 62 Otherwise, when compared with other high-risk groups, the course of HIV-1 infection in hemophilia is very similar. As in other risk groups, low CD4 lymphocyte levels are strong predictors of which specific person will become symptomatic. Pneumocystis carinii pneumonia (Fig. 106-12) was the most common presenting AIDS-defining condition in HIV-seropositive hemophilia patients before the advent of prophylaxis. Other opportunistic infections, such as candida esophagitis and cryptococcal meningitis/septicemia, are reported in this subgroup. Kaposi sarcoma, however, is a very rare presenting condition in persons with hemophilia. Non-Hodgkin lymphoma can occur late in the disease at an incidence of 5.5%. MLID93214045 63
Currently, as with other HIV-seropositive patients, persons with hemophilia who have CD4 lymphocyte counts <400–500 cells/ml can be considered for prophylactic zidovudine; in those with a count of <200 cells/mm3, Pneumocystis prophylaxis should be added. The use of antiretroviral drugs that are hepatotoxic may be more problematic in persons with hemophilia since many have pre-existing liver disease secondary to HCV. Thus, liver chemistries should be monitored carefully, especially in persons on combination antiretroviral therapy.
Virucidal Treatments of Concentrates
There is now a triple barrier to viral transmission through factor concentrates: (1) self-exclusion for donors, (2) donor screening, and (3) viral inactivation procedures. Self-exclusion includes asking the plasma donor detailed questions concerning hepatitis, possible HIV exposure, and general health (to elicit nonspecific symptoms of HIV infection). Donor screening now includes HCV testing, as well as serologic testing for HIV-1 and HBV.
Multiple methodologies for attenuating viruses during processing of factor concentrate have been devised. MLID89274385 64 They include heating the concentrate and the use of solvent/detergent combinations, which disrupt lipid-coated viruses such as HIV and some hepatitis viruses. MLID94054272 65,66
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