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Recent advances in clot biology and assessment of clotting

University of Lund, Sweden

Mirella Ezban

Biopharmaceutical Research Unit, Novo Nordisk A/S, Mäløv, Denmark, mie{at}novonordisk.com

Since the first description of the haemostatic process by Morawitz in 1904, knowledge about the haemostasis mechanism has undergone substantial modifications. Increasing knowledge of enzymology, purification and characterisation of coagulation proteins led to the introduction of the waterfall or cascade model of coagulation. However, these models were based on in vitro studies in the presence of artificial phospholipids and the absence of cells. Two pathways to achieve the formation of a haemostatic fibrin plug were identified, the so-called `extrinsic system' involving both factors present in the circulation and from the extravascular space, and the `intrinsic system' using only factors present in the circulation. However, with increasing knowledge about the interaction between factors from the two systems, the relevance of this model was questioned. The availability of recombinant FVIIa has made further research of the role of FVII/FVIIa and TF feasible, resulting in the current concept of haemostasis according to which the process principally occurs on two cell surfaces, the TF-bearing cell and the thrombin-activated platelet. A limited amount of thrombin is generated by the FVIIa-TF complex on the TF-bearing cell resulting in activation of platelets, FIX, FVIII and FV. The further and full thrombin generation then takes place on the activated platelet surface. The most frequently used assays for evaluation of the global haemostatic capacity are the prothrombin time (PT) and the activated partial thromboplastin time (APTT). The PT measures the formation of a fibrin clot in the presence of an abundance of TF thereby principally reflecting the initial thrombin generation dependent especially on FVII, FV and FX, while the APTT mimics the processes on the activated platelet surface involving FVIII, FIX, FXl, FV, FX and prothrombin. For more specific analyses, assay systems measuring the level of various coagulation factors are available. Platelet function is measured by platelet count and bleeding time. The platelet aggregation response to different agonists can be measured in special aggregometers. The usefulness of these techniques in evaluating a potential bleeding risk is, however, doubtful.

Key Words: coagulation • clotting • hemostasis • clotting assays • bleeding

Trauma, Vol. 10, No. 4, 261-270 (2008)
DOI: 10.1177/1460408608098295


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