Biochemical and in vivo properties of commercial virus‐inactivated factor VIII concentrates

Abstract

The following commercial virus‐inactivated factor VIII concentrates were studied in vitro: AHF‐Kabi and Octonativ, KabiVitrum; Hemofil T, Hyland; Factorate HP and Monoclate, Armour; Nordiocto, Nordisk Gentofte (dry heated); Kryobulin TIM3, Immuno (steam treated); Profilate, Alpha (heated as dry material slammed in heptane); Hemate P, Behring (wet heated) and Octa‐V.I., Octapharma (solvent/detergent treated). The concentration of VIII:C was lowest in AHF‐Kabi, whereas it ranged from 24 to 53 IU/ml in the high purity concentrates, except for Monoclate in which it ranged from 91–128 IU/ml. All concentrates but Octa‐V.I. had higher values for VIILAg than for VIII:C. von Willebrand factor with normal distribution of multimers could only be demonstrated in AHF‐Kabi and Hemate P. In vivo studies were performed in 12 severe hemophiliacs. Recovery and half‐life of VIILC did not differ between the various concentrates. Hemate P was given to 5 patients with severe von Willebrand's disease, in all of whom a correction of the hemostatic defect was seen.

A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate®P/ Humate®‐P: History and clinical performance

“…High‐purity FVIII products from human plasma and recombinant FVIII products, although substantially improving the treatment of HA, have not been adequate in treating VWD because they contain no or less‐than‐sufficient quantities of HMW‐VWF (112–116). Additionally, many VWD and HA patients have already been treated with DDAVP and shown to be unresponsive, or would have become unresponsive after several DDAVP doses.…”

“…The HMW multimers of VWF are thought to be critical in correcting the coagulation defects in patients with VWD (115, 137, 140, 148, 151–154). Multimer analyses have revealed that Haemate ® P contains relatively high levels of intermediate and HMW multimers of VWF, unlike most other VWF/FVIII products in which predominantly the lower and some intermediate‐molecular‐weight multimers are found (112–116, 155).…”

DDAVP‐induced enhancement of platelet retention: Its dependence on platelet‐von Willebrand Factor and the platelet receptor GP IIb/IIIa

“…DDA VP (MinirinO, Ferring, Sweden) (4 pg/ml) was dissolved in saline to a total volume of 10 ml and injected intravenously during 10 minutes at a dosage of 0.3 pg/kg. Hemate-P (Behring, Germany), a factor VIII concentrate containing native vWF (7), was injected intravenously during 20min at dosages shown in Table 1.…”

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].…”