In Vitro Thrombogenicity Tests of Factor IX Concentrates

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Abstract
Summary. Three different types of test were compared in characterizing the properties of thrombogenic material in factor IX concentrates. The thrombin generation time (TGt50) of Sas et al (1975), the non‐activated partial thromboplastin time (NAPTT) of Kingdon et al (1975) and the factor VIII inhibitor bypassing activity (FEIBA) of Elsinger (1975) were used. When concentrates were incubated with purified antithrombin III (At III), the NAPTT lengthened but no effect was seen with the TGt50 and FEIBA. The TGt50 showed thermal sensitivity both in the presence and absence of antithrombin III. When concentrates were treated with the serine protease inhibitor diisopropylfluorophosphate (DFP), the thrombogenicity appeared to decrease slightly in all three tests, but was not completely eliminated. Heparinagarose was found to adsorb the material(s) responsible for shortening the NAPTT and TGt50, and it also adsorbed factor IX. Gel filtration studies clearly separated the three activities into different sizes; the TGt50 activity was the largest with an apparent molecular weight of 1 × 106, FEIBA activity was intermediate with an apparent molecular weight of 1.30 × 105 and NAPTT activity was the smallest with an apparent molecular weight of 7 × 104. Our results show that the thrombogenicity measured by these three tests may be related to the presence of physically distinct materials.