Thrombosis research
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Thrombosis research · Jul 2012
The clinical significance of differences between point-of-care and laboratory INR methods in over-anticoagulated patients.
Patients receiving warfarin are at increased risk of bleeding when their International Normalised Ratio (INR) >4.5. Although not standardised above 4.5 the INR is measured in over-anticoagulated patients, consequently we have examined the reliability of INR results ≥4.5. We assessed: the relationship between different prothrombin time systems for INRs >4.5; the relationships between the INR and levels of vitamin K-dependent coagulation factors (VKD-CF) and thrombin generation test (TGT) parameters; and the impact that variation in results would have on warfarin dosing. ⋯ Our data suggest that CoaguChek XS Plus INRs >4.5 and <8.0 are comparable to laboratory INRs (both methods) and it is probably unnecessary to perform laboratory INRs for clinical management of patients with INRs >4.5 including those >8.0.
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Bleeding and thrombosis are the ultimate clinical outcomes of aberrations in the haemostatic process. Haemostasis prevents excessive blood loss due to the effort of various compartments like the vasculature, blood cells, coagulation and fibrinolysis. The complexity of all processes involved makes the diagnosis of aberrations difficult, cumbersome and expensive. ⋯ Despite years of research, such an assay is not yet available; however, some interesting candidates are under development and combine the effects of various compartments. This review describes the development of global haemostasis assays and summarizes the current state of the art of these haemostasis assays covering thrombin and plasmin generation, turbidity and thromboelastography/thromboelastometry. Finally, we discuss the applicability of global assays in clinical practice and we provide a future perspective on the ongoing development of automation and miniaturisation as it is our belief that these developments will benefit the standardization of global haemostasis assays.
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Thrombosis research · Jun 2012
The procoagulant properties of purified fibrinogen concentrate are enhanced by carbon monoxide releasing molecule-2.
Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate. ⋯ CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.
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Thrombosis research · May 2012
Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population.
PERC rule was created to rule out pulmonary embolism (PE) without further exams, with residual PE risk<2%. Its safety is currently not confirmed in high PE prevalence populations even when combined with low clinical probability assessed by revised Geneva score (RGS). As PERC rule and RGS are 2 similar explicit rules with many redundant criteria, we hypothesized that the combination of PERC rule with gestalt clinical probability could resolve this limitation. ⋯ PERC rule combined with low gestalt probability seems to identify a group of patients for whom PE could easily be ruled out without additional test. A larger study is needed to confirm this result and to ensure safety.
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Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. ⋯ This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.