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This study was carried out to assess the clinical efficacy in von Willebrand's disease (vWD) of a new, very high purity (VHP), solvent/detergent (SD)-treated, vWF concentrate (VHP Human von Willebrand Factor Concentrate, Biotransfusion) characterized by a high specific ristocetin cofactor (vWF:RCo) activity and a low factor VIII (FVIII) coagulant activity (FVIII:C). Nine patients (four type I, one type IIA, one type IIB, one type IIC, one type III and one acquired type II) were infused on 13 occasions including a pharmacokinetic study. Satisfactory haemostasis was achieved in all cases, including the treatment of spontaneous haemorrhages and the prevention of bleeding following surgery. The bleeding time was corrected for 6-12 h in 6/9 patients and shortened in the others. Furthermore, it was shown that the plasma vWF multimeric pattern of types II and III patients was greatly improved. When measured in eight patients 1 h after infusion, the vWF:RCo recovery was 77.3 (+/- 10.7)% while the F VIII:C recovery was strikingly higher (876 +/- 906%). This high recovery is likely related to the predominant 'pseudo-synthesis' of FVIII following the restoration of normal vWF levels. Maximum levels of FVIII:C occurred 6-12 h after the first infusion and normal levels of FVIII:C were maintained throughout the treatments with a dosage of 26-39 IU/kg vWF:RCo and only 0.2-5 IU/kg FVIII:C. The half-lives of the vWF-related parameters determined in a type III vWD patient were 20.6 h for vWF antigen, 17.8 h for vWF:RCo, 14 h for the high molecular weight multimers of vWF, 55.3 h for FVIII:Ag and 74 h for FVIII:C. In conclusion, it does not appear necessary that vWF concentrates intended for the treatment of vWD should contain FVIII in addition to vWF to be clinically effective in most patients.

It has been recently suggested that an acquired deficiency of proteins C and S could contribute to the pathogenesis of meningococcemic purpura fulminans (PF) in children. Our study was designed to measure the levels of antithrombin III (AT III), protein C, and protein S during adult PF and to determine the effects of an early infusion of high doses of AT III concentrates on clinical and biological alterations of PF. We studied five consecutive adult patients with meningococcemia (type B) and PF. The levels of AT III, protein C (antigen and activity), and protein S (total and free) were measured at admission and 24 h and 1 month later. The treatment included in each case: amoxycillin, dobutamine and high doses of AT III concentrates. All patients survived and were discharged without any sequelae. At admission, biological data were consistent with severely depressed protein C and protein S levels and moderately decreased AT III levels, without any discrepancy between protein C antigen and activity. After 24 h, AT III and protein S levels were within normal ranges, whereas protein C levels were still depressed. These data are consistent with the theory of a particular imbalance in the anticoagulant systems during meningococcemic PF, contrasting with the usual findings observed during septic disseminated intravascular coagulation. The possibility must be considered that high doses of one anticoagulant (AT III concentrates) could compensate for the acute decrease in the other (protein C system).

A case of myocardial infarction (MI) in a hemophilia B patient with a factor IX (FIX) inhibitor (6 BU) is described. MI occurred after two infusions of FEIBA concentrate. Unexpectedly, these infusions resulted in a neutralization of the inhibitor and a consistent plasma FIX activity which may have increased the thrombotic risks. Four days later, a psoas hematoma was suspected. At that time the inhibitor remained undetectable, allowing a therapy with purified FIX concentrates. No recurrence of thrombotic complication was observed. This is an additional illustration of the thrombotic risks associated with the use of activated prothrombin complex concentrates, especially in patients having pre-existing risk factors for thrombosis. The management of bleeding episodes in hemophilia B patients with inhibitor represents an especially difficult challenge.

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