title: Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.
abstract: Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability.
  
  
  
  Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL-1plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL-1FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences regarding FVII sensitivity exist between various thromboplastins used for VKA monitoring. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Therefore, thromboplastin choice may affect FVII-mediated INR stability.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Star-Medical Diagnostic Center, Rotterdam, the Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Biedermann
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: A M H P
authors.initials: AM
authors.lastname: van den Besselaar
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: M P M
authors.initials: MP
authors.lastname: de Maat
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.|Star-Medical Diagnostic Center, Rotterdam, the Netherlands.
authors.forename: M J H A
authors.initials: MJ
authors.lastname: Kruip
mesh_terms: D000925:Anticoagulants / Q000737:chemistry; D001681:Biological Assay; D001780:Blood Coagulation Tests; D005167:Factor VII / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000737:chemistry; D006490:Hemostatics / Q000737:chemistry; D006801:Humans; D019934:International Normalized Ratio; D010949:Plasma / Q000187:drug effects; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000737:chemistry; D013925:Thromboplastin / Q000737:chemistry*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006490:Hemostatics; C082196:Innovin; D011994:Recombinant Proteins; D014812:Vitamin K; D005167:Factor VII; D013925:Thromboplastin
keywords: International Normalized Ratio; coumarins; factor VII; hemostasis; phospholipids; thromboplastin