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Traces of factor VIIa modulate thromboplastin sensitivity to factors V, VII, X, and prothrombin
Author(s) -
SMITH S. A.,
COMP P. C.,
MORRISSEY J. H.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.01971.x
Subject(s) - thromboplastin , factor x , factor viia , factor vii , medicine , sensitivity (control systems) , coagulation , prothrombin complex , prothrombin time , tissue factor , thrombin , platelet , engineering , electronic engineering
Summary. Background: Thromboplastin reagents are used to conduct prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and screen for clotting factor deficiencies. Thromboplastins made from purified, recombinant tissue factor are generally more sensitive to changes in plasma factor (F) VII levels than are thromboplastins prepared from tissue extracts. This may be problematic as FVII's short plasma half‐life can result in day‐to‐day fluctuation during oral anticoagulant therapy. We hypothesized that trace contamination of tissue‐derived thromboplastins with FVII(a) blunts sensitivity to plasma FVII levels. Methods: Traces of purified FVIIa were added to thromboplastin reagents prepared using recombinant human tissue factor and the effect on sensitivity to individual clotting factors was quantified in PT clotting assays. Results and conclusions: Adding 5–100 p m FVIIa not only decreased thromboplastin sensitivity to plasma FVII, it surprisingly increased sensitivity to plasma levels of FV, FX and prothrombin. In addition, traces of FVIIa interacted with changes in the salt content and phospholipid composition of recombinant thromboplastins to further modulate their sensitivities to individual clotting factors. These results help explain how thromboplastin reagents of differing composition exhibit differing sensitivities to individual clotting factor levels. Implications of our results for monitoring oral anticoagulant therapy and other uses of the PT assay are discussed.