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Semin Thromb Hemost 2021; 47(01): 063-073
DOI: 10.1055/s-0040-1718888
Review Article

The Clotting Trigger Is an Important Determinant for the Coagulation Pathway In Vivo or In Vitro—Inference from Data Review

Shu He
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
2   Division of Coagulation Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
,
Honglie Cao
2   Division of Coagulation Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
,
Charlotte Thålin
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
,
Jan Svensson
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
,
Margareta Blombäck
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
2   Division of Coagulation Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
,
Håkan Wallén
1   Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
› Author Affiliations Funding This study is supported by the Clas Groschinsky fund.
› Further Information
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Abstract

Blood coagulation comprises a series of enzymatic reactions leading to thrombin generation and fibrin formation. This process is commonly illustrated in a waterfall-like manner, referred to as the coagulation cascade. In vivo, this “cascade” is initiated through the tissue factor (TF) pathway, once subendothelial TF is exposed and bound to coagulation factor VII (FVII) in blood. In vitro, a diminutive concentration of recombinant TF (rTF) is used as a clotting trigger in various global hemostasis assays such as the calibrated automated thrombogram, methods that assess fibrin turbidity and fibrin viscoelasticity tests such as rotational thromboelastometry. These assays aim to mimic in vivo global coagulation, and are useful in assessing hyper-/hypocoagulable disorders or monitoring therapies with hemostatic agents. An excess of rTF, a sufficient amount of negatively charged surfaces, various concentrations of exogenous thrombin, recombinant activated FVII, or recombinant activated FIXa are also used to initiate activation of specific sub-processes of the coagulation cascade in vitro. These approaches offer important information on certain specific coagulation pathways, while alterations in pro-/anticoagulants not participating in these pathways remain undetectable by these methods. Reviewing available data, we sought to enhance our knowledge of how choice of clotting trigger affects the outcome of hemostasis assays, and address the call for further investigations on this topic.

Keywords

coagulation cascade - assays - clotting trigger - thrombin generation - fibrin formation


Publication History

Article published online:
21 December 2020

© 2020. Thieme. All rights reserved.

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