In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A.

AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance study, 70 previously treated haemophilia A patients were included (73% severe, 14% moderate and 13% mild haemophilia A). Most of these patients were followed during 4 years for the appearance of adverse events, possible transmissions of blood-borne viruses and the occurrence of antibodies against FVIII. The efficacy of treatment was determined in each patient by the in vivo recovery of FVIII. During this study, only six adverse events, possibly related to the use of AAFACT, were reported. None of these were indicated as serious. Transmissions of HIV, HAV, HBV and HCV in the seronegative patients have not been observed. In none of the patients, inhibitors to FVIII were detected. The in vivo recovery of FVIII during this study was not different from the in vivo recovery observed in eight patients during the preregistration study. There was a correlation of in vivo recovery with age and body weight. From these results, we conclude that the clinical usage of this human plasma-derived FVIII product is efficient and safe.

Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction.

AIMS: Complement inhibition by C1-inhibitor has been shown to reduce myocardial ischaemia-reperfusion injury in animal models. We therefore studied the effects of intravenous C1-inhibitor, following reperfusion therapy, in patients with acute myocardial infarction. METHODS AND RESULTS: C1-inhibitor therapy was started not earlier than 6h after acute myocardial infarction, in order to prevent interference with thrombolytic therapy. A loading dose of C1-inhibitor was followed by a continuous infusion for 48 h, using three escalating dosage schemes. Efficacy of complement inhibition was estimated from C4 activation fragments. Plasma concentrations of myocardial proteins were compared to values measured in matched control patients. In 22 patients, C1-inhibitor was well tolerated and drug-related adverse events were not observed. Target plasma levels of C1-inhibitor were reached, with values of 48.2 ml.kg(-1) for distribution space and 35.5h for the half-life time of C1-inhibitor. A dose-dependent reduction of C4 fragments was found P=0.005). In 13 patients who received early thrombolytic therapy, release of troponin T and creatine kinase-MB(mass) was reduced by 36% and 57%P =0.001), compared to 18 controls. CONCLUSION: Continuous 48-h treatment with C1-inhibitor provides safe and effective inhibition of complement activation after reperfused acute myocardial infarction and may reduce myocardial injury.