Thromb Haemostasis
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Severe sepsis in children or adults may cause a life-threatening coagulopathy, with widespread consumption of activated protein C (APC); recombinant human APC (rhAPC) is a promising candidate anticoagulant treatment. We investigated the effects of rhAPC and other anticoagulants on coagulation triggered by adding small quantities of lipidated tissue factor to human umbilical-cord plasma in vitro. rhAPC, unfractionated heparin (UH), and melagatran (a direct thrombin inhibitor) were studied individually, and in combinations of rhAPC with either UH or melagatran. rhAPC alone dose-dependently prolonged the activated partial-thromboplastin time (aPTT) but not the prothrombin time (PT), and dose-dependently suppressed two indices of thrombin generation, namely prothrombin fragment F 1.2 (F 1.2) generation and thrombin-antithrombin (TAT) complex formation. UH alone dose-dependently prolonged the aPTT but not the PT, while melagatran alone dose-dependently prolonged both the aPTT and the PT. ⋯ Both the capacity of UH to prolong the aPTT and the capacity of melagatran to prolong the aPTT and the PT were augmented by adding rhAPC. In our in-vitro study, adding either UH or melagatran augmented the capacity of rhAPC to suppress thrombin generation in human umbilical-cord plasma, with the anticoagulant effect of melagatran being more predictable than that of UH. Hence, combining rhAPC with melagatran might be a valuable therapeutic option in patients with severe sepsis.
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Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. ⋯ For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.
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Excluding or confirming pulmonary embolism remains a diagnostic challenge. In elderly patients pulmonary embolism is associated with substantial co-morbidity and mortality, and many elderly patients with suspected pulmonary embolism are inpatients. The safety and efficacy of the combination of a clinical probability (CDR) and d-dimer test in excluding pulmonary embolism in this group is unclear. ⋯ In elderly outpatients the combination of a non-high CDR and a normal d-dimer result is a safe strategy to rule out pulmonary embolism. However, in inpatients this algorithm is not reliable to safely exclude pulmonary embolism. In addition, the proportion of patients >65 years in which this strategy excludes pulmonary embolism is markedly lower compared to younger patients.
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We recently demonstrated that patients with increased blood loss due to intraoperative coagulopathy show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration. We thus tested the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss in a study designed for diagnostic test evaluation in 168 patients admitted to the surgical service of our hospital. Intraoperative blood loss increased with preoperative fibrin monomer concentration (median blood loss of 50, 100, 200 and 400 ml in preoperative fibrin monomer quartile groups 1 to 4, p<0.001, ANOVA on ranks; interquartile comparisons p < 0.05 (4/6), Mann Whitney Rank Sum test). ⋯ Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration < 3 microg/l excluded intraoperative blood loss > 500 ml with 92% sensitivity and 95% negative predictive value. These results support our hypothesis that preoperative fibrin monomer concentrations are related to intraoperative blood loss in elective surgery. Fibrin monomer should be further investigated for it's potential to serve as a routine tool for preoperative risk stratification of intraoperative bleeding.