Safety Profile of Porcine Factor VIII and Its Use as Hospital and Home-Therapy for Patients with Haemophilia-A and Inhibitors: the Results of An International Survey

Abstract

SummaryA multicentre retrospective survey was conducted to re-assess the use of porcine factor VIII (HYATE:C), its side effects and the selection of patients for regular or home-therapy. 15,152,000 units of HYATE:C were used by 154 patients. The median inhibitor cross-reactivity to porcine VIIIC of 137 patients was 15%, 27% of patients lacking cross-reactivity. An absent, intermediate or brisk specific antiporcine anamnestic response was observed in 29, 40 and 31% of patients respectively. Seven patients were treated on-demand as home-therapy for a median 6.2, range 1.5-13 years. 23 further patients were treated regularly in hospital for a median of 3, range 2-7 years. This group used 8,319,000 U of porcine VIIIC for 2,000 bleeding episodes.The incidence of transfusion reactions was 0.001%, 0.64% and 2.3%, for domiciliary infusions, infusions in multiply treated inpatients, and unselected in-patient infusions, respectively. The risk of reactions was dose-related. A post-infusion fall in platelet count was common, but usually transient and clinically insignificant. This was also dose-related (r = -0.64, p = 0.002). Marked reductions in platelet count were occasionally seen, usually with intensive replacement therapy. The relative lack of side effects observed amongst patients treated at home is attributable to the low, median 33 U/kg, dose used by this group.A subgroup of inhibitor patients, identifiable by their absent or modest anamnestic response to porcine factor VIII may be treated regularly and safely with this product in small doses, over a period of years.

Toward optimal therapy for inhibitors in hemophilia

“…However, there have been reports of patients receiving plasmaderived porcine fVIII for extended periods of time without antibody cross-reactivity and with continued good clinical response. 15 Highdose human fVIII is an option for selected patients with a highresponding inhibitor that has decreased to a titer ,5 BU/mL at the time of a serious limb or life-threatening bleeding event. There have also been recent reports of improved thrombin generation ex vivo with combinations of fVIII and bypassing agents in samples from patients with hemophilia A and inhibitors and in vivo in a small pilot study.…”

Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction

“…Porcine-derived FVIII (pFVIII) is a therapeutic alternative for FVIII replacement in inhibitor patients whose antibodies have limited cross-reactivity with the pFVIII molecule [22]. Porcine FVIII can result in measurable FVIII replacement for patients whose inhibitors have less than 5 BU activity against pFVIII.…”

“…Unfortunately, inhibitors arising in patients with congenital hemophilia often present with crossreactivity high enough to prevent the effective use of pFVIII (i.e., inhibitor titers 5 BU or higher against pFVIII). Moreover, many patients in whom pFVIII is initially useful develop pFVIII antibodies after 5-10 days of treatment, limiting the usefulness of this product in controlling bleeds over the long term [22].…”

Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C)

“…Recombinant or puri®ed PvWF has been demonstrated to activate platelets and cause transmembrane signaling [5À7]. PFVIII is now prepared by ion-exchange chromatography with polyelectrolytes to remove most of the PvWF [23], and subsequently thrombocytopenia post-infusion has been mild and reversible [1,24,25]. However, as shown in the current study, small amounts of PvWF remain in the product; this may potentially be bene®cial in restoring hemostasis.…”