Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Jul 2005
Randomized Controlled TrialThe effects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass.
Systemic inflammation and the activation of the coagulation system following cardiopulmonary bypass (CPB) may contribute to postoperative complications. In vitro studies have demonstrated that heparin possesses anti-inflammatory properties. To ascertain the relative benefits of high versus low heparin doses, we studied the impact of varying heparin doses on the inflammatory response and coagulation system during and following CPB. ⋯ Higher heparin doses were associated with higher heparin concentrations during CPB. A high heparin dose achieved a better preservation of the coagulation system with less thrombin formation and platelet activation. The heparin dose had small influence on proinflammatory cytokines release.
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Blood Coagul. Fibrinolysis · Jun 2005
Multicenter StudyMulti-centre investigation on reference ranges for ROTEM thromboelastometry.
Reagent-supported thromboelastometry (TEM) with the ROTEM Whole Blood Haemostasis Analyser is an enhancement of thromboelastography, a method that is increasingly used for the point of care monitoring of acute perioperative bleeding disorders. We investigated the reference ranges of two activated tests (INTEM and EXTEM) and a test analysing specifically the fibrin component of coagulation (FIBTEM) in a multi-centre approach. The reference ranges obtained for the clotting time (CT), clot formation time (CFT), alpha angle (ALP), maximum clot firmness (MCF) and clot lysis parameters were comparable from centre to centre. ⋯ The repeatability (within-run imprecision) of the results was dependent on the test with the following coefficients of variation: 1-5% (clot firmness, alpha angle), 3-12% (CT, CFT), 6-13% (FIBTEM clot firmness). Citrated blood samples were stable for ROTEM analysis stored within 6 h from drawing. In summary, the data showed that ROTEM thromboelastometry yields consistent values between centres and that providing general orientating reference ranges seems to be possible.
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Blood Coagul. Fibrinolysis · Apr 2005
Randomized Controlled Trial Clinical TrialUsing thrombelastography to determine the efficacy of the platelet glycoprotein IIb/IIIa antagonist, roxifiban, on platelet/fibrin-mediated clot dynamics in humans.
The effect of platelet glycoprotein IIb/IIIa antagonists on the dynamics of platelet/fibrin clot formation and strength was determined using thrombelastography (TEG) under conditions of recalcification or tissue factor addition. In the present investigation, the effect of roxifiban (class I) on ex vivo clot dynamics using recalcified blood was tested in normal, healthy volunteers (n = 7) dosed with 1 mg BID roxifiban for 9 days. ⋯ These data suggest that a subthreshold blood level of 40-50 nmol/l roxifiban active form was achieved in those subjects, as estimated from an in vitro calibration with XV459. These data indicate (not studied) that roxifiban, at a targeted clinical dosing regimen, failed to achieve sufficient exposure to modulate platelet-mediated clot retraction.
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Blood Coagul. Fibrinolysis · Apr 2005
Comparative StudyPlasma levels of tissue factor and soluble E-selectin in sickle cell disease: relationship to genotype and to inflammation.
Microvascular occlusion, the pathophysiological hallmark of sickle cell disease (SCD), is a complex multifactorial process with alterations in coagulation, endothelial function and inflammation. However, relationships between these process in the two most common genotypes, HbSS and HbSC, are unknown. We hypothesized differences in the hypercoagulable state [as assessed by tissue factor (TF), fibrinogen and D-dimer], endothelial function [markers soluble E-selectin (sE-sel) and von Willebrand factor (vWf)], and inflammation [markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] in these two SCD genotypes. ⋯ Raised vWf in HbSS compared with HbSC may be important in determining pathophysiology in these two genotypes. Positive correlations between IL-6 and TF in both HbSC and HbSS disease leads us to speculate that inflammation may be important in coagulation activation in these patients, or vice versa. However, lack of correlation of sE-sel with inflammatory markers implies that other mechanisms are responsible for increased levels of this marker of endothelial activation.
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Blood Coagul. Fibrinolysis · Apr 2005
P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose.
A large variability in the antiplatelet response to clopidogrel has been consistently reported. Recently, a P2Y12 haplotype was shown to be associated with enhanced adenosine diphosphate (ADP)-induced platelet aggregation in healthy volunteers. The aim of this study was to test in patients (n = 416) scheduled for coronary artery stenting whether P2Y12 haplotype H2 carriage is associated with increased ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. ⋯ Haplotype combinations and genotypes were not associated with parameters of ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Maximal ADP (5 mumol/l)-induced platelet aggregation was similar in patients carrying haplotype H2 and homozygous carriers of haplotype H1 (43.9 +/- 21.4 versus 43.2 +/- 21.1%, respectively; P = 0.77). Carriage of P2Y12 H2 haplotype does not seem to affect the platelet response to a 600 mg loading dose of clopidogrel in coronary artery disease patients prior to stenting.