Studies of the prothrombin activation pathway utilizing radioimmunoassays for the F2/F1 + 2 fragment and thrombin--antithrombin complex

Abstract

We have evaluated the efficacy of utilizing radioimmunoassays (RIAs) for prothrombin activation fragments (F2/F1 + 2) and for thrombin-- antithrombin complex (TAT) in purified systems and in whole blood. During venipuncture, appropriate anticoagulants were employed in order to prevent the generation of thrombin and factor Xa. The RIAs were shown to be specific for F2/F1 + 2 as well as TAT and did not interact with other plasma components. Initially, thrombin generation was studied in a purified human system of prothrombin, antithrombin, factor Xa, and factor V as well as phospholipid and Ca++. Under these conditions, the kinetics of F2/F1 + 2 and TAT generation were virtually superimposable. However, when factor V was omitted from the reaction mixture, a significantly greater amount of F2/F1 + 2 as compared to TAT was observable. Subsequently, prothrombin activation was monitored during the spontaneous coagulation of freshly drawn blood. Throughout the entire course of thrombin generation, the observable rate of formation of F2/F1 + 2 was considerably greater than that of TAT. We have examined the levels of F2/F1 + 2 and TAT in normal individuals. Our studies indicate that the concentrations of F1 + 2 and TAT average 1.97 nM and 2.32 nM, respectively. We have also quantitated the concentrations of F2/F1 + 2 and TAT in patients with disseminated intravascular coagulation. In these individuals, the levels of both components are elevated. However, the ratio of F1 + 2 to TAT ranges from 2.37 to 5.55. Thus, we conclude that under in vivo conditions, prothrombin activation is characterized by the accumulation of a stable precursor, such as prethrombin-2, and that this phenomenon may be related to an alteration of factor V function.

Haemostatic and fibrinolytic factors in men with a small abdominal aortic aneurysm

“…The coagulation cascade involves a complex series of enzymatic reactions that culminate in thrombin generation and the deposition of insoluble fibrin. TAT complex and prothrombin F1 + 2 are established markers for thrombin activation 30 , whereas the action of plasmin on crosslinked fibrin generates degradation products including D-dimer. Epidemiological data suggest that fibrinogen and D-dimer levels independently predict the presence of an AAA 31 ; however, as baseline aortic diameter was not measured in the present study the temporal nature of this association remains uncertain.…”

Efficacy and safety of desloratadine combined with dipyridamole in the treatment of chronic urticaria

“…The prothrombin activation fragment F 1+2 is an index of in vivo thrombin generation; one molecule of F 1+2 is released with the generation of each thrombin molecule. [20][21][22] Anticoagulation suppresses the F 1+2 level in a dose-response fashion. 23 It has been shown that CU patients showed high blood coagulation state with F 1+2 levels higher than normal.…”

Novel and diagnostically applicable information from optical waveform analysis of blood coagulation in disseminated intravascular coagulation

“…However, the frequent need for serial samples on a patient to highlight changes in one or more of the laboratory parameters inevitably delays the diagnosis and initiation of appropriate therapeutic intervention. Although more specific assays, which are generally centred around thrombin generation and its consequence (Heeb et al, 1989;Teitel et al, 1982), are available, the practical need for systems that are robust, simple and rapid in performance precludes their use in the acute clinical setting.…”