Phospholipid composition controls thromboplastin sensitivity to individual clotting factors

Abstract

To cite this article: Smith SA, Comp PC, Morrissey JH. Phospholipid composition controls thromboplastin sensitivity to individual clotting factors. 2006; 4: 820-7. Summary. Background: Tissue factor is the active ingredient in thromboplastin reagents used to perform prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and to screen for clotting factor deficiencies. Thromboplastins are complex mixtures prepared from extracts of brain or placenta, although newer thromboplastins contain recombinant tissue factor incorporated into phospholipid vesicles. Thromboplastins can vary widely in their sensitivity to reductions in the levels of vitamin K-dependent clotting factors. A system to compensate for this, the International Sensitivity Index (ISI) and International Normalized Ratio (INR), has revolutionized the monitoring of oral anticoagulant therapy. The INR system is also sometimes used to monitor coagulopathies in patients with sepsis or liver failure, applications for which it was not originally designed and for which it has not been rigorously validated. Objectives: To better understand thromboplastin performance, we systematically investigated which properties of recombinant thromboplastins influence their sensitivities to changes in the levels of specific clotting factors. Results: We now report that relative sensitivities to changes in the plasma levels of factors V, VII, X (FV, FVII, FX) and prothrombin are differentially influenced by a recombinant thromboplastin's content of phospholipid and sodium chloride. Furthermore, thromboplastins of similar ISI values may exhibit quite different sensitivities to each of these clotting factors. Conclusions: Differing sensitivities of thromboplastin reagents to individual clotting factor levels have implications for monitoring of oral anticoagulant therapy and interpreting results of the PT assay. J Thromb Haemost

Aortic thrombosis in dogs: Presentation, therapy, and outcome in 26 cases

“…42 Binding of canine clotting factors to human tissue factor has been demonstrated to be decreased compared to the binding of human clotting factors to human tissue factor, the interaction from which thromboplastin sensitivity and the ISI are in part derived. 42,43 To the authors' knowledge, there is no data currently available on thromboplastin sensitivity to canine clotting factors or on an ISI specific for canine samples. It has been demonstrated that correcting PT clotting data by the INR may not produce equivalent results when clotting times are measured using different thromboplastin reagents, 42 so it is unclear to what degree the INR values were affected in the patients in this study considering different laboratories using different thromboplastin reagents were utilized.…”

“…The ISI was developed to compensate for differences in thromboplastin potency to human clotting factors. 42 Thromboplastin reagents are comprised of tissue factor from crude extracts of animal or human tissue origin, or recombinant human tissue factor. 42 Binding of canine clotting factors to human tissue factor has been demonstrated to be decreased compared to the binding of human clotting factors to human tissue factor, the interaction from which thromboplastin sensitivity and the ISI are in part derived.…”

“…42 Thromboplastin reagents are comprised of tissue factor from crude extracts of animal or human tissue origin, or recombinant human tissue factor. 42 Binding of canine clotting factors to human tissue factor has been demonstrated to be decreased compared to the binding of human clotting factors to human tissue factor, the interaction from which thromboplastin sensitivity and the ISI are in part derived. 42,43 To the authors' knowledge, there is no data currently available on thromboplastin sensitivity to canine clotting factors or on an ISI specific for canine samples.…”

Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome

“…fibrinogen, factors II, VII, IX and X) in blood samples from anticoagulated patients play an important role in explaining discrepancies between the different INR test methods [26]. Additionally, the tissue factor content, the phospholipid composition and differences in ISI calibration may contribute to differences observed in the INR measurements using different thromboplastins [5,9,14].…”

“…Thromboplastin reagents contain either recombinant tissue factor or tissue factor extracted from the brain and placental sources [8]. Thromboplastins also vary in the type and amount of the phospholipid component, which has been shown to influence the results of PT testing [9]. With regard to the phospholipid composition used in the test system, the presence of antiphospholipid antibodies (APL) in a patient's plasma sample may have important implications for the dosing of VKA therapy due to an overestimation of the INR.…”