The Coagulant Active Phospholipid(Pl) Content Of Prothrombin Complex Concentrates(Pcc) Is A Critical Determinant Of Their In Vivo Thrombogenicity

It has generally been assumed that the thrombogenicity of PCC relates to their invariable contamination by activated products of their component clotting factors. In earlier studies we demonstrated a lack of correlation between the activated clotting factor content ᶓ in vivo thrombogenicity of some PCC. In contrast, in vitro measurement of coagulant active PL content appeared to be a more reliable determinant of subsequent in vivo activity. In recent studies we have confirmed the presence of PL of known coagulant activity in PCC ᶓ studied its activity both in vitro ᶓ in vivo after its extraction from the parent PCC. PCCs were obtained from various agencies or prepared in our laboratory to a standard protocol either from fresh frozen plasma or plasma obtained from outdated platelet concentrates. Each was assayed for Xa (S-2222) ᶓ PL (thrombin generation assay with DAPA) ᶓ an index of thrombogenicity in vivo determined in a stasis model in rabbits. There was a significant correlation between the latter ᶓ PL (r=0.8727 p<0.01) but not Xa. Thin layer chromatography of an ethanol ether extract of the most thrombogenic PCC showed the presence of PL known to be coagulant active including Phospho- tidylserine ᶓ -choline. This extract retained full PL replacing activity in the DAPA assay in vitro but was non- thrombogenic in vivo. When, however, a highly purified preparation of Xa was added, in the same relative proportions as in the parent PCC, thrombogenicity in vivo was restored. It is concluded that the content of coagulant active PL is a critical determinant of the potential thrombogenicity of PCC in vivo. It appears to act in concert with Xa ᶓ conceivably, other serine proteases perhaps by protecting them from inactivation by AT III. This may explain why relatively “non-activated” PCCs may still be associated with thromboembolic complications.