Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parallel group, international multicenter trial. Patients were randomly allocated to treatment A: 35 mu kg-1 or B: 70 mu kg-1, in blocks of 2. Within each block, one patient was assigned to the 35 mu kg-1 dosing regimen and the other to 70 mu kg-1 dose. One hundred and fifty subjects from 20 sites were screened for this study and 116 had baseline assessments. Of these, 84 were treated on the protocol and 32 were not treated in the study, in most cases because they did not return to the clinic with an eligible bleeding episode. One hundred and seventy-nine bleeding episodes were treated, of which 145 (81%) were acute haemarthroses. Both treatments were efficacious, with 71% having an excellent (59% and 60%) or effective (12% and 11%) response. Overall, the mean and median number of doses given per episode of joint bleeding were 3.1 and 2, respectively. The mean number of doses was 3.1 for the 70 mu kg-1 group and 2.7 for the 35 mu kg-1 group (P value = 0.142). The study concluded that rFVIIa in a dosage of 35 mu kg-1 or 70 mu kg-1 is both safe and reasonably effective in the treatment of joint or muscle haemorrhages in haemophilic patients with inhibitor antibodies to factor VIII or factor IX. It is concluded that the appropriate dose for the treatment of joint and peripheral muscle bleeding in haemophilic patients with inhibitors is 35-70 mu kg-1 given at 2-3 h intervals until haemostasis is achieved.

According to their caregivers, boys with hemophilia and HIV infection showed considerable resilience with regard to adaptive behavior and emotional and behavioral problems. However, over time changes occurred in these areas that appear to be related to immune functioning.

SummaryThe North American Immune Tolerance Registry was initiated to study of immune tolerance (ITT) in Canada and the United States with respect to: 1) therapeutic regimens in use for haemophilia A (HA) and B (HB) inhibitor patients; 2) therapeutic outcomes; 3) potential predictors of successful outcome and 4) complications of therapy. Data on 188 ITT courses was collected by questionnaire from 60 haemophilia centers from 1993-99. Among the completed courses, the overall ITT success rate was 70% (115/164) for all HA and 31% (5/16) for all HB. Outcome parameters noted to be predictive of ITT success for all HA were 1) pre-ITT induction (p = 0.003), 2) ITT peak (p = 0.007) and 3) historical pre ITT peak (p = 0.04) inhibitor titres. An inverse correlation between total daily dose (units/kg/day) and success: (80% with under 50; 71% with 50-99; 73% with 100-199; and 41% with ≥ 200, p = 0.01) was found. Outcome predictors were not evaluable for HB, although adverse reactions to therapy, including nephrotic syndrome, and access complications were more common among failed courses. Infection most often complicated the use of access catheters. These results are discussed within the context of the international ITT registry and upcoming prospective ITT study.

Results suggest caregivers perceive psychosocial problems in HIV+ youths with hemophilia and their families; some problems are specifically associated with greater immune compromise.

SummarySix brands of normal reference plasma produced in the United States, with assigned assay values for factor VIII and IX and, in four instances, ristocetin cofactor and von Willebrand antigen, were assayed in nine coagulation laboratories in academic institutions in the same country. Differences in mean assays of reference plasmas, as a percent of labelled potency, were significant and were greater than differences among laboratories. Standard methods of assigning potency to commercial reference plasmas are recommended.