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Standardization and clinical utility of thrombin-generation assays.

Berntorp, Erik LU and Salvagno, Gian Luca LU (2008) In Seminars in Thrombosis and Hemostasis 34(7). p.670-682
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Seminars in Thrombosis and Hemostasis
volume
34
issue
7
pages
670 - 682
publisher
Thieme
external identifiers
  • WOS:000262221700011
  • PMID:19085768
  • Scopus:58149084459
ISSN
1098-9064
DOI
10.1055/s-0028-1104546
language
English
LU publication?
yes
id
bf17e89c-006e-4f1f-8ff9-55d77158fec4 (old id 1276163)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19085768?dopt=Abstract
date added to LUP
2009-01-09 12:00:08
date last changed
2016-10-13 04:36:39
@misc{bf17e89c-006e-4f1f-8ff9-55d77158fec4,
  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.},
  author       = {Berntorp, Erik and Salvagno, Gian Luca},
  issn         = {1098-9064},
  language     = {eng},
  number       = {7},
  pages        = {670--682},
  publisher    = {ARRAY(0xbe06160)},
  series       = {Seminars in Thrombosis and Hemostasis},
  title        = {Standardization and clinical utility of thrombin-generation assays.},
  url          = {http://dx.doi.org/10.1055/s-0028-1104546},
  volume       = {34},
  year         = {2008},
}