Studies on the effect of heat treatment on the thrombogenicity of factor IX concentrates in dogs

Abstract

This study examines the effects of heat treatment for 72 h at 80 degrees C on the potential thrombogenicity of lyophilized human coagulation factor IX concentrates. Since heating generated minor amounts of thrombin, concentrate was prepared with antithrombin III addition prior to heat treatment. Changes in coagulation parameters were followed prior to and after infusion of 100 iu/kg of heated and unheated concentrates to dogs. All batches produced a transient fall in platelet count during infusion and a delayed rise in plasma fibrinopeptide A, accompanied by a minor prolongation of the activated partial thromboplastin time. Such changes were less marked for heated batches. Control infusion of a 'failed' factor IX concentrate showed an additional fall in fibrinogen, rise in fibrin degradation products and a more rapid rise in fibrinopeptide A, while thrombin infusion caused an even more dramatic intravascular coagulation. These studies indicated no increase in the potential thrombogenicity of freeze dried factor IX concentrates as a result of heat treatment.

Effects of Plasma Collection Systems and Processing Parameters on the Quality of Factor IX Concentrate1

“…Following the work of other groups [17], we are at present evaluating these products in an animal model to assess thrombogenicity in a more physiological situation. As has been pointed out [18], this is especially important as the in vitro thrombogenicity tests used by fractionation and clinical laboratories may have little bearing on the actual behavior of products in the in vivo situation.…”

In vivo Models of Thrombogenic Potential: Usefulness and Limitations

“…The methodology involved in a canine nonstasis model is shown in Figure 1 [5,6]. It can be seen that the blood volume permits sequential sampling over a sustained period.…”

The manufacture of blood plasma products in Scotland: a brief history

“…A modification to Factor II, IX & X concentrate in 1985 enabled heat treatment to be applied which was effective against both HIV and HCV, with product being issued as soon as studies on freedom from thrombogenic reactions had been completed. 13 A high purity Factor VIII concentrate and a fibrin sealant kit were both developed in 1992 and high purity Factor IX and a heat-treated fibrinogen concentrates in 1993. The demand for plasma products continued to increase with use of Factor VIII concentrate doubling and output of IV IgG increasing 10-fold during this period.…”