title: Heparin-induced inhibitory effects of a prothrombin complex concentrate on global tests of haemostasis.
abstract: Prothrombin complex concentrates (PCC) have been used as bypassing agents for the treatment of haemophilia A patients with inhibitor as well as for replacement therapy in congenital and acquired deficiencies of vitamin-K-dependent clotting factors. The efficacy of PCC is variable, however, especially during long-term and high-dose use, and all currently available products of this nature contain heparin. We have examined the haemostatic properties of PCC using reconstituted whole blood made by mixing coagulation-factor-deficient plasma and washed blood cells. In rotation thromboelastometry (ROTEM), the recommended therapeutic dose of Proplex ST corrected the abnormal patterns. At higher concentrations, however, the ROTEM patterns regressed. In addition, specific assays of coagulation factors appeared unreliable in the presence of 2.5 U/ml Proplex ST; the abnormalities were corrected when protamine sulfate was added. The findings suggest that the presence of heparin in PCC might have a greater effect on global haemostasis. Careful attention to the anticoagulant effect as well as thrombogenicity of PCC is required. Monitoring therapy using such as ROTEM analysis could be highly informative.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Nogami
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanaka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takeda
authors.forename: John C
authors.initials: JC
authors.lastname: Giddings
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshioka
mesh_terms: D001779:Blood Coagulation Factors / Q000032:analysis / Q000037:antagonists & inhibitors*; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D016903:Drug Monitoring / Q000592:standards; D006487:Hemostasis; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D006493:Heparin