A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma

Shu He; Kun Zhu; Mika Skeppholm; Jenny Vedin; Jan Svensson; Nils Egberg; Margareta Blombäck

doi:10.1160/TH06-07-0370

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 871-882
DOI: 10.1160/TH06-07-0370

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma

Shu He

¹Karolinska Institutet: Department of Clinical Science, Danderyds Hospital, Royal Institute of Technology, Stockholm, Sweden

⁴Department of Molecular Medicine & Surgery, Coagulation Research, Royal Institute of Technology, Stockholm, Sweden

,

Kun Zhu

⁶Department of Numerical Analysis and Computer Science, Royal Institute of Technology; Stockholm, Sweden

,

Mika Skeppholm

²Karolinska Institutet: Division of Cardiology and Danderyds Hospital, Royal Institute of Technology, Stockholm, Sweden

,

Jenny Vedin

⁵Department of Cardiothoracic Surgery & Anaesthesia and Royal Institute of Technology, Stockholm, Sweden

,

Jan Svensson

¹Karolinska Institutet: Department of Clinical Science, Danderyds Hospital, Royal Institute of Technology, Stockholm, Sweden

³Karolinska Institutet: Division of Clinical Chemistry, Danderyds Hospital, Royal Institute of Technology, Stockholm, Sweden

,

Nils Egberg

⁴Department of Molecular Medicine & Surgery, Coagulation Research, Royal Institute of Technology, Stockholm, Sweden

,

Margareta Blombäck

¹Karolinska Institutet: Department of Clinical Science, Danderyds Hospital, Royal Institute of Technology, Stockholm, Sweden

⁴Department of Molecular Medicine & Surgery, Coagulation Research, Royal Institute of Technology, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

The global assay of Overall Haemostasis Potential we previously described has been refined. The coagulation cascade in plateletpoor plasma is triggered by adding a minimal dose of recombinant tissue factor together with purified phospholipids and calcium; fibrinolysis is initiated by adding recombinant tissue type-plasminogen activator in a concentration similar to what can be obtained during thrombolysis. Numerical differentials of optical densities reflecting rates of fibrin formation and degradation are calculated by a new software, and the Coagulation Profile (Cp) and the Fibrinolysis Profile (Fp) are determined. The combined effect of these counteractive systems is expressed as a ratio of Cp to Fp, called the Overall Haemostasis Index. Commercially available coagulant-deficient patient plasma samples and plasma with various amounts of added PAI-1 are examined; changes of fibrin turbidity demonstrate that this assay can determine Cp and Fp in a physiologically relevant way. Increased Cp and decreased Fp in prothrombotic patients, as well as expected effects of heparin or a thrombin inhibitor on Cp and Fp, suggest that our method can detect hypercoagulability and assist in monitoring antithrombotic treatment. Ongoing studies will show whether this simple assay can be of value in clinical routine.

Keywords

Global assay - reaction rate determination - haemostasis balance - hypercoagulability - anticoagulation

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References

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