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

Abstract

Cryoprecipitate has proved to correct the hemostatic defects in von Willebrand’s disease (vWD) and platelet-type vWD. However, recent studies have revealed that transmission of the AIDS retrovirus (HIV) occurs through exposure to blood products including cryoprecipitate. Treatment with heat-treated factor VlII/von Willebrand factor (vWf) concentrates may have certain advantages over treatment with nonheated products, if these preparations are efficacious in these disorders. We found that a commercially available factor VIII/vWf concentrate, Haemate P, contained the high-molecular-weight multimers of vWf and had a ratio of ristocetin cofactor (RCof) to vWf antigen (vWf: Ag) close to unity. In addition, its capacity to directly induce aggregation of platelet-type vWD platelets in vitro was similar to that for cryoprecipitate. When infused into a patient with platelet-type vWD, Haemate P shortened the prolonged bleeding time and caused spontaneous platelet aggregation in vitro with a mild diminution of platelet count. These results indicate that some of the heat-treated factor VIII/vWf concentrates may provide a safer, yet still effective, treatment for platelet-type vWD.

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].…”

An intermediate‐purity factor VIII concentrate supports platelet adhesion under flow conditions

“…Von Willebrand factor antigen and RiCof activities have been evaluated in a series of intermediate-and highpurity FVIII:C concentrates [10,11]. One of the ®rst intermediate-purity factor VIII plasma derivatives commercially available that was known to retain vWF activities corrected ristocetin platelet aggregation when added to platelet-poor plasma from vWD patients [29]. The biochemical and safety characteristics of the concentrate prompted several investigators to test it in vWF-de®cient patients, with good clinical results [4,30].…”

Haemate®P von Willebrand factor/factor VIII concentrate: 25 years of clinical experience

“…Haemate P is characterized by its high content of VWF, with a ratio of approximately 2.4 IU VWF:ristocetin cofactor activity (VWF:RCo) for each IU of FVIII:C. So although Haemate P was first developed for use in haemophilia A patients, reports of its use in VWD began appearing by the mid to late 1980s [20,[35][36][37][38][39][40][41]. Prior to the availability of Haemate P, it was generally believed that FVIII concentrates were not effective in VWD because of the absence of high molecular weight (HMW) VWF multimers in the concentrate preparations.…”

“…Normally, the HMW multimers of VWF perform this function, and their presence is particularly important in the initial phase of haemostatic thrombus formation in areas under high shear stress [44]. Starting in the 1980s, there have been numerous demonstrations of the consistent presence of HMW VWF multimers in batches of Haemate P [37,38,40,42,[45][46][47][48][49][50][51]. Moreover, in comparison with other available commercial VWF-containing concentrates, Haemate P has the highest content of HMW VWF multimers [38,41,42,50,51].…”