Phospholipid composition controls thromboplastin sensitivity to individual clotting factors

S. A. Smith, P. C. Comp, James H. Morrissey

Research output: Contribution to journalArticlepeer-review


Background: Tissue factor is the active ingredient in thromboplastin reagents used to perform prothrombin time (PT) clotting tests tomonitor 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 varywidely 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 tomonitor coagulopathies in patients with sepsis or liver failure, applications forwhich 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 valuesmay 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.

Original languageEnglish (US)
Pages (from-to)820-827
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Issue number4
StatePublished - Apr 2006


  • International normalized ratio
  • International sensitivity index
  • Prothrombin time
  • Tissue factor

ASJC Scopus subject areas

  • Hematology


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