Patients with mild haemophilia A may have a discrepancy in the factor VIII (FVIII) level when measured with a one-stage assay (FVIII:C1) compared with a two-stage assay (FVIII:C2). This discrepancy usually results in the one-stage level being higher than the two-stage level. A F8 mutation resulting in a Tyr346-->Cys substitution within the a1 interdomain region has been described which results in the converse assay discrepancy. We report four individuals (three families) who have this mutation. Mean FVIII:C1 level was 25 IU dL(-1) compared with a mean FVIII:C2 level of 63 IU dL(-1). These individuals had presented opportunistically and did not have a clinically significant bleeding disorder. The bleeding phenotype correlated with the two-stage assay result rather than the one-stage result. FVIII replacement therapy does not appear to be required for these individuals.

Low-dose streptokinase has been established as an alternative to surgery in selected patients with acute peripheral arterial ischaemia. Tissue plasminogen activator (t-PA) is responsible for normal plasma fibrinolytic activity and has recently become available for clinical use owing to recombinant DNA technology. It has the theoretical advantage of fibrin specificity, which may result in enhanced thrombolytic effects with greater safety. Twenty-three patients with recent lower limb arterial occlusions received t-PA over a tenfold range of concentrations and five patients received low-dose streptokinase. One month after treatment with t-PA or streptokinase 19 (68 per cent) patients had limb salvage, five (18 per cent) had required amputations and four (14 per cent) had died. Systemic fibrinolytic effects were variable but basically dose related. Haemorrhage occurred most frequently at the highest t-PA concentration and was major in four (17 per cent) cases, including a fatal stroke. Plasma fibrinogen concentration fell below 1.2 gl-1 in five (22 per cent) patients who received t-PA and was found to be a significant risk factor for haemorrhage, t-PA was an effective thrombolytic agent at all concentrations studied. The dose currently used in clinical studies at this institution is 0.5 mg h-1.

We describe a case where danaparoid was used prophylactically in a high-risk twin pregnancy following the development of heparin-allergy while on prophylactic dalteparin. Danaparoid was substituted for dalteparin at 20 weeks of pregnancy following the development of a severe skin reaction while on the low molecular weight heparin. Although there was no significant fall in platelet count, an aggregation assay for heparin-induced thrombocytopaenia was positive. The skin lesions rapidly resolved following the change to subcutaneous danaparoid. Delivery was by emergency caesarian section at 35 weeks under a general anaesthetic, as a dose of danaparoid had been given 6 h prior to delivery. A sample of breast milk showed no anti-activated factor X activity. Danaparoid was continued post-delivery until the patient was fully warfarinized. To our knowledge, there are no previous reports of the use of danaparoid in this setting.