The half-life of porcine factor VIII in patients with no detectable inhibitor was reported to be very similar to that of human factor VIII and in the range 8–12 h [6,10,12]. Thrombocytopenia and allergic reactions in association with porcine factor VIII therapy were a concern ever since the first crude preparations were used in the 1950s. These primitive products were acknowledged to contain an unspecified ‘Platelet Aggregating Factor’. Clinicians reported at the time that patients often complained

of flashes of light in their eyes after infusions of animal plasma, which was attributed to clumps of platelets passing through retinal blood vessels [5b]. Although, much purer than previous formulations, factor VIII only accounted for around 1% of the total protein in Hyate:C [13]. Adverse effects were still selleck products observed following Hyate:C infusions, but the incidence and severity were much lower in association with the use of this purer product [14,15]. However, the possibility of such reactions led some physicians to express reservations about the use of this particular product for home treatment. In one detailed review of adverse

events, the observations related to 283 infusions of porcine FVIII given to 30 subjects over a decade were reported [16]. There was a median percentage fall in the baseline platelet count of 54% (range 8–86%). In the case Selleckchem CT99021 4-Aminobutyrate aminotransferase of

10 courses, the subsequent drop was more severe with nadirs ranging 10–99 × 109/L (median 67). Allergic reactions were seen in 15 of 30 patients (50%), in 20 of 63 courses (32%). The symptoms were generally mild and included fever, flushing, urticaria and shivering, but five courses were accompanied by more severe anaphylactoid reactions. The observed thrombocytopenia was shown to be caused by residual traces of porcine von Willebrand factor (VWF) in the concentrate [17]. Porcine VWF binds to the glycoprotein Ib receptor on platelets, leading to activation of the glycoprotein IIb/IIIa receptor, which in turn causes to platelet aggregation associated with binding of fibrinogen [18]. Flow cytometry also demonstrated activation of platelets following treatment with Hyate:C, reflected by an increase in the number of circulating platelets expressing CD62 and CD63 and annexin V [19]. The authors of this study speculated that the platelet activation caused by infusion of porcine factor VIII enhanced haemostasis through a quite separate, but complementary pathway to that simply because of increased circulating factor VIII. Hyate:C was not subjected to any specific viral inactivation steps, such as pasteurization or solvent/detergent treatment during manufacture, unlike conventional plasma-derived products derived from human plasma.