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Circulating antibodies to factor VIII (anti-VIII, “inhibitors”) occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post- infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.

SummaryAn inhibitor to clotting factor VIII (anti-VIII: C) developed in a 70 year old woman with carcinoma of the pancreas three months after palliative by-pass surgery. A life-threatening sublingual haemorrhage was controlled by infusion of human factor VIII concentrate in high dosage. With the objective of reducing pancreatic tumour size, combination cytotoxic therapy with fluorouracil and CCNU was given. Reduction in the size of the tumour was associated with disappearance of anti-VIII:C, reappearance of normal quantities of clotting factor VIII (VIII: C) in the plasma and resolution of the bleeding tendency. The anti-VIII: C was characterised as being predominantly of the IgG4 sub-class with k light chains. In vitro and in vivo studies showed the inactivation of VIII: C by anti-VIII: C was markedly non-linear. Normal quantities of factor VIII coagulant antigen (VIII: CAg) were detected in the patient’s plasma when VIII: C levels were negligible.

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Two unusual variants of von Willebrand's Disease (vWD) have been observed; one resembling Type Ic vWD and one an unclassified variant form of the disease. Both are associated with a history of mild bleeding and with a prolonged bleeding time.Two related patients (father and daughter) presented with reduced vWF activity (RiCoF) and vWF:Ag. Multimer analysis showed the presence of all molecular weight multimers but with a lack of triplet structure. This was confirmed in 3% agarose gels and resembled the pattern of multimers previously described as Type Ic vWD. Both patients responded well to DDAVP.In the second case the patient had a lowered vWF activity (RiCoF) but normal vWF:Ag, analogous to a Type Ila vWD pattern. Mutimer analysis however demonstrated the presence of all MW multimers with a normal triplet structure. This defect was not detected with two monoclonal antibodies that recognise the GPIb binding site on vWF and is thought to represent a minor abnormality in the vWF molecule in this patient.