Mechanism of inhibition of prothrombinase by TFPIα. TFPIα inhibits thrombin generation by prothrombinase during the initiation phase of coagulation (A) but not during the propagation phase (B). This inhibition is mediated by the interaction of K2 with the active site of FXa (yellow), as well as the interaction of the TFPIα basic C terminus (blue) with the B-domain acidic region (red), present in FXa-activated FVa and some forms of platelet-released FVa (green). This region is absent in thrombin-activated FVa. Based on the model of Bos and Camire,¹²⁷  it may be hypothesized that the TFPIα basic region and FVa B-domain acidic region bind to the FVa heavy chain A2 domain (expanded box). Modified from Wood et al⁵  with permission.