In vitro evaluation of factor VIII--bypassing activity of activated prothrombin complex concentrate, prothrombin complex concentrate, and factor VIIa in the plasma of patients with factor VIII inhibitors: thrombin generation test in the presence of collagen-activated platelets. 1993

Y Sultan, and F Loyer
Laboratoire d'Hémostase, Hôpital Cochin, Paris, France.

Clinical efficacy of plasma-derived products with factor VIII--bypassing activity in patients with factor VIII inhibitors is difficult to evaluate. It is also difficult to predict efficacy by coagulation assay. A test of thrombin generation in defibrinated plasma and in the presence of activated platelets was used to test the bypassing activity of the most currently used products (activated prothrombin complex concentrate from various origins, prothrombin complex concentrate, and factor VIIa). The bypassing activity was evaluated in the absence and presence of tissue factor. In plasma with inhibitor, activated prothrombin complex concentrate elicited dose-dependent thrombin formation, whereas prothrombin complex concentrate and factor VIIa induced only minimal thrombin activity. Addition of tissue factor in the assay elicited thrombin generation in the presence of factor VIIa and prothrombin complex concentrate and allowed additional thrombin formation in the presence of activated prothrombin complex concentrate. Although it is hazardous to extend results of in vitro testing to clinical efficacy, our study sheds some light on the mechanism of action of the various substances used to treat bleeding episodes in patients with factor VIII inhibitors.

UI MeSH Term Description Entries
D001779 Blood Coagulation Factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Clotting Factor,Coagulation Factors,Blood Coagulation Factor,Clotting Factors,Coagulation Factor,Coagulation Factor, Blood,Coagulation Factors, Blood,Factor, Coagulation,Factors, Coagulation,Factor, Blood Coagulation,Factor, Clotting,Factors, Blood Coagulation,Factors, Clotting
D005169 Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Coagulation Factor VIII,Factor VIII Clotting Antigen,Factor VIII Coagulant Antigen,Factor VIII Procoagulant Activity,Thromboplastinogen,Blood Coagulation Factor VIII,F VIII-C,Factor 8,Factor 8 C,Factor Eight,Factor VIIIC,Hyate-C,Hyatt-C,F VIII C,Hyate C,HyateC,Hyatt C,HyattC
D006441 Hemoglobin A Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D013925 Thromboplastin Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. Antigens, CD142,CD142 Antigens,Coagulation Factor III,Factor III,Tissue Factor,Tissue Thromboplastin,Blood Coagulation Factor III,Coagulin,Glomerular Procoagulant Activity,Prothrombinase,Tissue Factor Procoagulant,Urothromboplastin,Activity, Glomerular Procoagulant,Factor III, Coagulation,Procoagulant Activity, Glomerular,Procoagulant, Tissue Factor,Thromboplastin, Tissue
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015942 Factor VIIa Activated form of factor VII. Factor VIIa activates factor X in the extrinsic pathway of blood coagulation. Coagulation Factor VIIa,Factor VII, Activated,Blood Coagulation Factor VII, Activated,Factor 7A,Factor Seven A,Activated Factor VII,Factor VIIa, Coagulation
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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