Coagulation Inhibitor Potential: : a global assay for the detection of thrombophilia
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AbstractThrombophilia can be defined as an increased, persistent tendency to venous thrombosis. It can be acquired or inherited. The annual incidence of venous thrombosis is about 1 per 1000 in the adult population. Inherited thrombophilia may be caused by several genetic defects that mostly result in deficient inhibition of coagulation in the blood. Deficiencies of the natural coagulation inhibitors antithrombin (AT), protein C (PC) and protein S are rare and can be found in less than 1 % of the general population. Factor V (FV) Leiden and prothrombin gene mutation are clinically less severe causes of inherited thrombophilia. In northern Europe the prevalence of FV Leiden is about 5-10 %. Among acquired risk factors for venous thrombosis are use of oral contraceptives and postmenopausal hormone therapy.
The main aim of this study was to develop a global assay that could be used to detect a thrombophilic condition in blood samples. This could limit the need for multiple blood tests.
In the Coagulation Inhibitor Potential (CIP) assay coagulation in blood plasma is activated by tissue factor and fibrin polymerisation is monitored. In a parallel sample the inhibition of activation is potentiated by pentasaccharide and the snake venom Protac, which activate AT and PC in the blood. The effect of potentiated inhibition of coagulation is calculated.
Plasma samples from persons with inherited thrombophilia had deficient inhibition of coagulation. Women who received hormone therapy to prevent ill effects of the menopause had in many cases a similar reaction pattern. This may relate to the increased risk of venous thrombosis. A cooperation with foreign scientists verified earlier results. The CIP assay proved superior to two other global assays as to their ability to detect inherited thrombophilia. The CIP method can be used to detect thrombophilia with high sensitivity and specificity. It can also be used as a tool for further research.
List of papers
I. Andresen MS, Iversen N, Abildgaard U. Overall haemostasis potential assays performed in thrombophilic plasma: the effect of preactivating protein C and antithrombin. Thromb Res. 2002 Dec 15;108(5-6):323-8. Abstract.
II. Andresen MS, Abildgaard U, Liestol S, Sandset PM, Mowinckel MC, Odegaard OR, Larsen ML, Diep LM. The ability of three global plasma assays to recognize thrombophilia. Thromb Res. 2004;113(6):411-7. Abstract.
III. Andresen MS, Abildgaard U. Coagulation Inhibitor Potential: a study of assay variables. Thromb Res. 2005;115(6):519-26. Abstract.
IV. Andresen MS, Eilertsen AL, Abildgaard U, Sandset PM. Hormone therapy and raloxifene reduce the coagulation inhibitor potential. Blood Coagul Fibrinolysis. 2007;18:455-60. Abstract.