title: Identification of prothrombin as a major thrombogenic agent in prothrombin complex concentrates.
abstract: Prothrombin complex concentrates (PCC) were compared in an in vitro test system for thrombogenicity (thrombin generation assay) employing plasma from coumarin-treated patients. Among these concentrates one had a proven history of thrombogenicity, whereas the remainder did not cause such fatal casualties in the past. Investigations into the thrombogenic component were performed by spiking experiments in which we biased a typical PCC without reported thromboembolic complications into one with a performance in the thrombin generation assay like that with a proven history of thrombogenicity. Hereby, it was possible to identify prothrombin as the most plausible thrombogenic component. Additional experiments performed with anticoagulant components (antithrombin together with heparin) resulted in a perfect reversal of the observed in vitro thrombogenicity. Our in vitro observations corroborate on an experimental basis the widespread medicinal usage of antithrombin administration as a regimen for the avoidance of thromboembolic complications during treatment with PCC and related products, and vice versa. Our observation casts doubts upon the widely accepted idea of activated factor IX as the thromboembolic agent in PCC. Also, our finding may be taken as an example for the feasibility of this test system as an in vitro model for thrombogenicity.
authors.affiliation: Paul Ehrlich Institut, Langen, Germany.
authors.forename: Christine Hanker
authors.initials: CH
authors.lastname: Dusel
authors.forename: Claudia
authors.initials: C
authors.lastname: Grundmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eich
authors.forename: Rainer
authors.initials: R
authors.lastname: Seitz
authors.forename: Herbert
authors.initials: H
authors.lastname: König
mesh_terms: D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use; D015949:Factor IXa / Q000737:chemistry; D002836:Hemophilia B / Q000628:therapy; D006801:Humans; D010949:Plasma / Q000737:chemistry; D011516:Prothrombin / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry*
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D011516:Prothrombin; D015949:Factor IXa; D013917:Thrombin