title: 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.
abstract: The global assay of Overall Haemostasis Potential we previously described has been refined. The coagulation cascade in platelet-poor 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.
authors.affiliation: Karolinska Institutet, Department of Clinical Science, Royal Institute of Technology, Stockholm, Sweden. he_shu@yahoo.com
authors.forename: Shu
authors.initials: S
authors.lastname: He
authors.forename: Kun
authors.initials: K
authors.lastname: Zhu
authors.forename: Mika
authors.initials: M
authors.lastname: Skeppholm
authors.forename: Jenny
authors.initials: J
authors.lastname: Vedin
authors.forename: Jan
authors.initials: J
authors.lastname: Svensson
authors.forename: Nils
authors.initials: N
authors.lastname: Egberg
authors.forename: Margareta
authors.initials: M
authors.lastname: Blombäck
authors.forename: Hakan
authors.initials: H
authors.lastname: Wallen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000378:metabolism; D001777:Blood Coagulation; D005337:Fibrin / Q000096:biosynthesis* / Q000378:metabolism*; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D008875:Middle Aged; D010743:Phospholipids / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012984:Software; D013925:Thromboplastin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D010743:Phospholipids; D011994:Recombinant Proteins; D005337:Fibrin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator