Premium
Thrombomodulin Inhibits Tissue factor Mediated Thrombin Generation in blood and Prothrombin Complex Concentrates
Author(s) -
Fareed Jawed,
Hoppensteadt Debra,
Syed Daneyal,
Kahn Daniel,
Mosier Michael,
Kaul Inder
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.609.11
Subject(s) - thrombomodulin , thrombin , tissue factor , fibrin , chemistry , thrombin generation , coagulation , platelet , immunology , medicine
A recombinant thrombomodulin (Recomodulin, Asahai Kasei, Tokyo, Japan) is currently used for the management of DIC and related disorders. Beside inhibiting thrombin and forming complexes with this enzyme, Recomodulin (RM) mediates its therapeutic effects involving modulation of inflammatory processes and thrombogenesis. The purpose of this study is to determine the effect of RM on thrombin generation in plasma and prothrombin complex concentrates. RM (2.02 mg/ampule) was commercially obtained. Working solutions of buffered RM were prepared at 100ug/ml. Tissue factor mediated generation of thrombin and its inhibition in normal human plasma (NHP) (n=25), platelet rich plasma (PRP) (n=25) and various prothrombin complex concentrates such as Beriplex, Cofact, Feiba, Konyne, Octaplex, Preconativ, Profilnin, Prothromplex ( 1u/ml) were investigated utilizing a fluorometric thrombokinetics method. The effect of RM on thrombin mediated fibrinokinetics was also measured using an optical method. RM produced a concentration dependent inhibition of thrombin generation in all systems. In the NHP the IC50 was 0.29 + 0.06 ug/ml in contrast to PRP where the IC50 was 1.99 + 0.31 ug/ml. The inhibition of thrombin generation in various PCCs was also concentration and product dependent. Marked inhibition was noted in Preconativ, Prothromplex and Beriplex. RM also inhibited the fibrin formation in both the PRP and NHP system in a differential manner. These results suggest that beside the direct inhibition of thrombin, RM is capable of inhibiting thrombin generation in a matrix dependent fashion and is also capable of modulating fibrin formation as evident by fibrinokinetic studies.