Hemostatic effect of a heat-treated factor VIII concentrate (Haemate P) in von Willebrand's disease

Abstract

A heat-treated factor VIII (F VIII) concentrate (Haemate P) has been administered to patients with various types of von Willebrand's disease (vWD). The 4 activities of F VIII/vWF as well as change in the multimeric structure of vWF were then studied. In 4 patients with type I vWF who were given a Ristocetin cofactor (Rcof) dose of 42-78 U/kg, there was a clear reduction of the bleeding time and an increase of F VIII: C, F VIII: Ag, Rcof and vWF: Ag for several hours. The recovery of Rcof. after 1 h was 50-75%. Although the multimeric composition of vWF in these patients was similar to that of normal plasma, the density of each multimer band was very low. After infusion, however, the density of all multimer bands increased for several hours, to decrease again after 24 h. In 4 patients with type II A vWD who received a dose of Rcof of 55-76 U/kg, the 4 activities of F VIII/vWF increased similarly as was the case in type I. All patients had only 3-4 smaller multimer bands. New larger and intermediate multimers appeared for several hours after infusion of the preparation. Two patients with type III vWD who received doses of Rcof of 52 and 65 U/kg showed also a similar increase in the 4 activities of F VIII/vWF after infusion. All the multimers lacking in these patients appeared for several hours after infusion.

Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study

“…Overall mean in vivo incremental recoveries for VWF:RCof (2.7 IU/dL per IU/kg) and for FVIII:C (2.1 IU/dL per IU/kg) were similar to values reported for these and other FVIII/VWF concentrates. [8][9][10][11][12] The mean half-life of FVIII:C in patients with VWD, approximately 24 hours, was substantially longer than the half-life seen in patients with hemophilia A, approximately 12 hours. This is because Patients with type 3 VWD were administered, in random order, 1 infusion of either A-SD or A-SD/HT at a dose of 60 IU/kg WF:RCof, followed 7 or more days later by an identical infusion of the other preparation.…”

“…Virally attenuated plasma-derived FVIII/VWF concentrates, originally developed for the treatment of hemophilia A, are used in desmopressinunresponsive patients. [8][9][10][11][12] A prospective study of replacement therapy in VWD has not been previously conducted. Therapy has been largely empirical, not tailored to different VWD types, and it has been based primarily on FVIII for dosing recommendations.…”

Experience with Haemate P in von Willebrand’s Disease in Adults

“…Reports of successful use of Hae mate P in vWD were also published by Scharrer and Vigh [5], Takahashi et al [6], Czapek et al [7], Fukui et al [1], Vigh et al [8], Berntorp and Nilsson [2], Ieko et al [9], Rose et al [10], Logan [11], Mannucci et al [12], Rodeghiero et al [13], Yoshioka et al [14], and Foster [15], Several other new FVIII concentrates look promising for treatment of vWD. Successful use of SD-FVIII concentrates and other FVIII preparations were reported by Furlan et al [16], Gazengel et al [ 17], Mazurier et al [18], Logan and Higgins [ 19], Pasi et al [20], Palmer et al [21], Cumming et al [22], Lawrie et al [23], Oates et al [24], Retzios et al [25], and Hanna et al [26].…”

Heat-Treated Factor VIII/von Willebrand Factor Concentrate in Platelet-Type von Willebrand’s Disease

“…These findings indicate that factor VIII/vWf con centrates which contain the high-molecularweight vWf multimers would be hemostati cally effective in platelet-type vWD. In addi tion, Fukui et al [29] have quite recently reported the hemostatic effectiveness of Haemate P in type I, IIA and III vWD. Treatment with these heat-treated concen trates would have some advantages over treatment with nonheated cryoprecipitate, since these concentrates are highly purified preparations and the heat treatment results in the inactivation of human immunodefi ciency virus [13],…”