Abstract
Blood coagulation occurs efficiently on cell surfaces such as activated platelets
and monocytes, and fibroblasts. It is initiated by limited amounts of 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, including FVIIa-TF as well as factors Xa and IXa
as they are formed in subsequent steps. For sustained normal coagulation to proceed,
effective in vivo activation of factor X requires the participation of factor IXa
generated via the FVIIa-TF complex. This may, in part, be due to effective inhibition
of factor Xa and FVIIa-TF complex by tissue factor pathway inhibitor that results
in blockage of direct activation of factor X by the FVIIa-TF complex. Additional generation
of factor Xa at injury sites may then proceed via the FIXa-VIIIa pathway. Thrombin
generated from prothrombin via complex formation 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 current understanding of how blood clots in vivo, it is clear
that both prothrombin time (PT) and activated partial thromboplastin time (APTT) are
highly artificial in vitro systems with major limitations. Nevertheless, these tests
are quite useful as global screening tests for abnormalities in the intrinsic or extrinsic,
as well as common, pathways of coagulation and for monitoring of anticoagulant therapy.
Keywords:
Extrinsic coagulation - intrinsic coagulation - activated partial thromboplastin time
- prothrombin time - monitoring anticoagulant therapy
