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Introduction In a previous study we followed up a cohort of haemophiliac patients infected with HIV and described the natural course of HIV infection in these patients. [1] This follow [...]

Individuals who are over the age of 30 and infected with the human immunodeficiency virus (HIV) progress more rapidly to the disease state of AIDS than younger individuals. The progression to AIDS has been linked to a decrease in the number of CD4+ helper T lymphocytes, a subset of immune cells which are destroyed by HIV. The progression to AIDS was analyzed over a 10-year period in 111 hemophiliacs who were infected with HIV. After being infected with HIV and having antibodies in their blood for seven years, 50 percent of the individuals over 30 years of age had developed AIDS, while only 12 percent of those aged 10 through 19 years old developed full-blown AIDS during the study period. The number of CD4+ cells were analyzed in the two groups. The number of CD4+ cells did not drop more rapidly in older individuals than in younger individuals. Older individuals appear to have a greater risk of progression to AIDS than younger individuals, even if the number of CD4+ cells is similar. The therapeutic implications are that treatment, especially as prophylaxis against opportunistic infections, should begin at higher CD4+ counts in older individuals than in younger individuals. (Consumer Summary produced by Reliance Medical Information, Inc.)

Hemophilia type A is an inherited bleeding disorder that is caused by a deficiency of factor VIII (a blood protein required for blood clot formation). An acquired form of hemophilia can develop in nonhemophiliacs when the immune system begins making autoantibodies that inhibit the activity of a small portion of the factor VIII molecule called factor VIII:C. This antibody is known as factor VIII:C inhibitor. Acquired hemophilia has been treated by giving intravenous injections of purified factor VIII:C. The clinical effectiveness of this form of treatment is related to the amount of factor VIII:C inhibitor present in the blood. Factor VIII:C purified from pig (porcine) blood has been used because it is less likely to react with the factor VIII:C inhibitors present in the patient's blood than factor VIII:C purified from human blood. This means that less of the porcine factor VIII:C will interact with the inhibitors (autoantibodies) and more will be available to prevent bleeding. Transfusion reactions are rare following treatment with porcine factor VIII:C. Adverse reactions of any type to porcine factor VIII:C occur in 7 to 13 percent of patients, and most of these reactions are mild or transient. Severe reactions are uncommon. Using porcine factor VIII:C instead of human factor VIII:C reduces the transmission of AIDS and hepatitis. (Consumer Summary produced by Reliance Medical Information, Inc.)

This study was designed to determine whether venous thrombosis is associated with a characteristic pattern in the plasma concentrations of fibrinopeptides and platelet alpha granule proteins. Patients undergoing elective craniotomy for tumor or vascular abnormality were studied prospectively for venous thrombosis with the 125I-fibrinogen uptake test and with daily measurement of the plasma concentrations of FPA (fibrinopeptide A), TIFPB (thrombin-increasable fibrinopeptide B reflecting Bβ 1-42), and βTG (β-thromboglobulin). Eighteen patients developed venous thrombosis and 14 did not. In the 14 patients who did not develop thrombosis, the mean FPA level was highest on the day after surgery and exceeded the TIFPB level so that the ratio of FPA to TIFPB, which is ≤0.5 in normals, was 1.2. During the next 14 days, both FPA and TIFPB levels were elevated, but the FPA/TIFPB ratio was not significantly different from the preoperative value. βTG and PF4 levels showed no clear pattern of change in the postoperative period. In 10 of the patients who developed thrombosis, the time of onset of thrombosis was documented by a change in the leg scan from negative to positive. In these 10 patients, the mean FPA level rose to equal the TIFPB level, producing an FPB/TIFPB ratio of approximately 1.0 for the 4 days preceding the change of the leg scan from negative to positive (p< 0.001). Changes in the βTG and PF4 levels were not statistically significant. We interpret the FPA and TIFPB levels as a distinct pattern that reflects sustained imbalance between thrombin and plasmin proteolysis of fibrinogen in association with the development of venous thrombosis. The finding of such sustained imbalance between FPA and TIFPB levels suggests that thrombosis is associated with impaired plasmin formation and/or action in addition to excessive fibrin formation. The finding that this pattern was evident several days before the leg scan became positive strongly supports efforts to develop a prognostic blood test. The blood tests used in this study showed adequate sensitivity, but low specificity for the detection of asymptomatic thrombosis. For this reason we suggest that use of these tests be confined to investigating the pathophysiology of thrombosis.

Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31 % for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI :C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.