Probable regulation of factor VIIa-tissue factor and prothrombinase by factor Xa-TFPI and TFPI in vivo.
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.
Gouin-Thibault
I
I
Department of Pathology, McMaster University, Hamilton, Canada.
Dewar
L
L
Craven
S
S
Kulczycky
M
M
Wun
T C
TC
Ofosu
F A
FA
D000328:Adult; D000925:Anticoagulants / Q000378:metabolism*; D000990:Antithrombin III / Q000378:metabolism*; D001777:Blood Coagulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D015942:Factor VIIa / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013925:Thromboplastin / Q000378:metabolism*
D000925:Anticoagulants; D008074:Lipoproteins; D010446:Peptide Fragments; C051928:lipoprotein-associated coagulation inhibitor; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D013925:Thromboplastin; D015942:Factor VIIa