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.
Circulating antibodies to factor VIII (anti-VIII, “inhibitors”) occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post- infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.
Circulating antibodies to factor VIII (anti-VIII, “inhibitors”) occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post- infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.