Polyelectrolyte Fractionated Porcine Factor VIII Concentrate In The Treatment Of Haemophiliacs With Antibodies To Factor VIII: C

Abstract

Antibodies to procoagulant factor VIII (anti-VIII:C) occurring in patients with haemophilia neutralise porcine factor VIII:C less readily than human factor VIII: C in vitro. Porcine factor VIII concentrate (porcine VIII) therefore has potential advantages in the treatment of such patients. Polyelectrolyte-fractionated porcine VIII (PE porcine VIII) lacks a major drawback of earlier preparations of porcine VIII in that it contains negligible quantities of platelet aggregating factor (PAF). The purpose of this study was to make a preliminary clinical assessment of the therapeutic value of PE porcine VIII. Over 6 months, 12 courses of treatment were given to four patients with circulating anti-VIII: C. Bleeding episodes treated ranged from the potentially lethal to moderately severe joint and muscle haemorrhages. Duration of courses was from 24 hrs. to more than 3 weeks. Clinical responses were strikingly good and no patient developed thrombocytopenia. Occasional mild pyrogenic-type transfusion reactions were encountered, but these were easily controlled. Dose- response relationships were most favourable in patients with low pre-infusion levels of anti-VIII: C activity against PE porcine VIII but excellent clinical responses could be obtained without achieving high plasma VIII: C levels. Multiple courses of therapy (up to 6) were given to individual patients without evidence of loss of clinical or laboratory efficacy, or an increased tendency to adverse reactions. There was no evidence of resistance in the patient who was treated daily for more than 3 weeks. Only 1 course of therapy was followed by a classical anamnestic rise in anti-VIII: C, and this course had included human factor VIII. PE porcine VIII appears to have a low immunogenic potential, and is a rational and effective therapeutic alternative for patients with anti-VIII: C.

Acquired Factor VIII Inhibitors: Pathophysiology and Treatment

“…Most of the autoantibodies in acquired hemophiliacs have minimal inhibitory activity against porcine FVIII, leading to its successful use in these patients. 27,29,30 A Bethesda assay detecting the inhibitory activity of the patient's antibody to porcine VIII was used to determine those patients likely to respond to porcine FVIII. Unfortunately, porcine FVIII is no longer commercially available, but a recombinant, porcine, B domain-deleted FVIII molecule (OBI-1, Octagen) has been shown to neutralize antibodies to human FVIII in vitro and is currently in phase II clinical trials.…”

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.…”

The Evidence behind Inhibitor Treatment with Porcine Factor VIII

“…The first publication gave a detailed description of 45 treatment courses in eight inhibitor patients, a total of 297 infusions [1]. Where no cross-reactivity to porcine Lee FVIII was detectable, the mean increment in plasma FVIII was 1.29 IU/dl per IU/kg of porcine factor VIII administered.…”

“…In addition, patients with acquired haemophilia usually respond well to porcine FVIII, particularly when they have low or absent anti-porcine inhibitor titres. In general, patients with inhibitor titres of !20 BU/ml have a better response rate than those with higher titres [1]. Some patients with congenital haemophilia maintain low antiporcine inhibitor titres over long term use and can therefore be treated routinely at home over many years.…”

“…The first published clinical experience with polyelectrolyte fractionated porcine FVIII concentrate in the treatment of haemophilic patients with antibodies to FVIII was reported in 1984 [1]. It is of interest that the first patient to be treated in 1980 is still using this treatment as home therapy.…”