Literatür Detay Bilgisi
Thrombin inhibition profiles in healthy individuals and thrombophilic patients.
Yazarlar : Rühl H, Müller J, Harbrecht U, Fimmers R, Oldenburg J, Mayer G, Pötzsch B.
Yayın : Thromb Haemost.
Yayın Yılı : 2012
Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22274722
Konu : Tromboz
Literatür İçeriği :
Abstract
Inhibition of thrombin by endogenous inhibitors plays a central role in the spatiotemporal control of clot formation. A failure to adequately inactivate thrombin such as in antithrombin deficiency generates a strong prothrombotic phenotype. To study if and to what extent delayed thrombin inactivation rates beyond antithrombin deficiency contribute to the prothrombotic phenotype we measured thrombin inhibition profiles in plasma samples obtained from 16 healthy individuals and 39 thrombophilic patients, including 17 patients diagnosed positive for anti-prothrombin/phospholipid antibodies. To test thrombin inhibition, thrombin was added to plasma, and endogenous thrombin inhibition stopped by addition of the reversible thrombin inhibitor argatroban. Subsequently, the amount of argatroban-complexed thrombin was measured using an oligonucleotide-based enzyme capture assay. In normal human plasma thrombin at concentrations up to 4 ng/ml (109 pM) became inactivated with an average half-life time of 56.4 ± 4.7 seconds (s). In antithrombin-deficient plasma the thrombin half-life was prolonged to 168.2 ± 14.9 s. Among the thrombophilic patients, only one with mild antithrombin deficiency showed impaired thrombin inactivation rates, whereas all other patients including the antiphospholipid positive patients showed thrombin inhibiting capacities within the normal range. We conclude that thrombin added to normal human plasma at subthreshold levels of ~100 pM or below becomes inactivated with a half-life time below 1 minute. Antiphospholipid antibodies do not prolong thrombin half-life times, making it unlikely that delayed thrombin inactivation contributes to the thrombotic phenotype of the antiphospholipid syndrome. In contrast, plasma levels of antithrombin falling below 80% of normal markedly prolong the thrombin half-lifeKonusu Aynı Olan Diğer Materyaller
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