Probable regulation of factor VIIa–tissue factor and prothrombinase by factor Xa–TFPI and TFPI in vivo Journal Articles uri icon

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abstract

  • Given that factor VIIa–tissue factor (TF) probably initiates coagulation in vivo, this study investigated the relationship between plasma concentrations of factor VIIa and prothrombin fragment 1+2 in plasma (the latter as an index of prothrombinase activity in vivo). The relationships between these two parameters and the concentrations of tissue factor pathway inhibitor (TFPI) and factor Xa–TFPI in plasma were also investigated. TFPI inactivates factor Xa in a reaction accelerated by heparin, whereas factor Xa–TFPI inactivates factor VIIa–TF and prothrombinase. Established enzyme‐linked immunosorbent assays (ELISAs) were used to quantify TFPI and prothrombin fragment 1+2, whereas we developed an ELISA to quantify factor Xa–TFPI using affinity purified rabbit (anti‐human TFPI)‐IgG and chicken anti‐(human factor Xa–TFPI)‐IgY as the capture and detector antibodies, respectively. Plasma factor VIIa was quantified using truncated tissue factor. The concentrations of factor VIIa and prothrombin fragment 1+2 increased in parallel in the plasmas of up to 145 healthy adults assayed (P = 0.007), as did the concentrations of factor VIIa and TFPI (P = 0.0039), and prothrombin fragment 1+2 and TFPI (P = 0.013). In contrast, there was an inverse relationship between the concentrations of free factor Xa–TFPI and factor VIIa (P <0.0001) and free factor Xa–TFPI and prothrombin fragment 1+2 (P=0.0095). These results are consistent with factor Xa–TFPI regulating factor VIIa–tissue factor and prothrombinase in vivo.

authors

  • Gouin‐Thibault, Isabelle
  • Dewar, Lori
  • Craven, Sharon
  • Kulczycky, Myron
  • Wun, Tze‐Chein
  • Ofosu, Frederick A

publication date

  • December 1996