ABSTRACT
Thrombin generation is a key process that determines the extent of a hemostatic plug
or a thrombotic process. The ensuing thrombin burst is crucial for the formation of
a stable fibrin clot. During its active life, thrombin exerts a multitude of highly
regulated actions on the blood and the vessel wall, including the clotting of fibrinogen.
The inappropriate generation of thrombin may lead to pathologic processes, foremost
of which are hemorrhagic or thrombotic diseases. The coagulation system is usually
investigated by means of two in vitro classic clotting tests, the activated partial
thromboplastin time (APTT) and prothrombin time (PT), which assess only time to initiation
of clot formation and do not entirely reflect global hemostatic balance. The APTT
and PT permit identification of connectivity between the component activities identified
as required for plasma coagulation and define the concept of intrinsic and extrinsic
coagulation pathways, which converge at the point of formation of the prothrombinase
complex. However, the mechanisms established by in vitro tests are not always mirrored
in the human pathologies associated with bleeding or thrombosis. The recent development
of newer tests based on the continuous registration of thrombin generation under in
vitro conditions that mimic more closely what occurs in vivo prompt a reinvestigation
of the balance between procoagulants and anticoagulants in patients with various hemostatic
disorders. Thrombin-generation assays not only provide an overall assessment of hemostasis
but also target potential extrahemostatic effects of the generated thrombin, a potent
agonist of a multitude of cellular activation pathways. Moreover, estimation of an
individual's thrombin-generation potential may correlate more closely with a hypercoagulable
or hypocoagulable phenotype when compared with traditional coagulation tests. In this
review, we discuss to what extent thrombin generation can be expected to reflect the
clotting function of blood, the development and use of different thrombin-generation
assay systems suitable for detecting changes in the kinetics of thrombin generation,
and the clinical utility of thrombin generation.
KEYWORDS
Thrombin-generation assay - coagulation - thrombin - endogenous thrombin potential
- APTT - PT
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Gian Luca SalvagnoM.D.
Sezione di Chimica e Microscopia Clinica, Dipartimento di Scienze Morfologico-Biomediche
Università degli Studi di Verona, Ospedale Policlinico G.B. Rossi, Piazzale Scuro,
10, 37134 – Verona, Italy
Email: gsalvagno77@yahoo.it
Email: gianluca.salvagno@univr.it
