New insights into how blood clots: Implications for the use of APTT and PTas coagulation screening tests and in monitoring of anticoagulant therapy

Blood coagulation occurs efficiently on cell surfaces such as activated pla telets and monocytes, and fibroblasts. It is initiated by limited amounts o f tissue factor (TF) exposed at the sites of vascular injury that complexes with trace amounts of circulating factor VIIa (FVIIa). Additional FVIIa-TF complexes are formed from FVII-TF involving positive feedback loops, inclu ding FVIIa-TF as well as factors Xa and IXa as they are formed in subsequen t steps. For sustained normal coagulation to proceed, effective in vivo act ivation of factor X requires the participation of factor Ma generated via t he FVIIa-TF complex. This may, in part, be due to effective inhibition of f actor Xa and FVIIa-TF complex by tissue factor pathway inhibitor that resul ts in blockage of direct activation of factor X by the FVIIa-TF complex. Ad ditional generation of factor Xa at injury sites may then proceed via the F IXa-VIIIa pathway. Thrombin generated from prothrombin via complex formatio n of prothrombin with FXa and FVa on phospholipid surfaces (prothrombinase complex) powerfully accelerates coagulation by activation of FVIII and FV, and sustains coagulation through activation of FXI. Thus, in light of our c urrent understanding of how blood clots in vivo, it is clear that both prot hrombin time (PT) and activated partial thromboplastin time (APTT) are high ly artificial in vitro systems with major limitations. Nevertheless, these tests are quite useful as global screening tests for abnormalities in the i ntrinsic or extrinsic, as well as common, pathways of coagulation and for m onitoring of anticoagulant therapy.