Thromb Haemostasis
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Inflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. ⋯ Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients.
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Clinical use of non-vitamin K antagonist oral anticoagulants is increasingly well established. However, specific agents for reversal of these drugs are not currently available. It was to objective of this study to investigate the impact of activated prothrombin complex concentrate (aPCC) on the anticoagulant effects of dabigatran in a randomised, controlled, porcine trauma model. ⋯ Thromboembolic or bleeding effects were not detected. In conclusion, blood loss following trauma in dabigatran-anticoagulated pigs was successfully reduced by 50 U/kg aPCC. Optimal methodology for measuring amelioration of dabigatran anticoagulation by aPCC is yet to be determined.
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Comparative Study Observational Study
Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer.
Venous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). ⋯ The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot microstructure and greatest VTE risk.
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Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants.
Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. ⋯ More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.
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The thromboelastometry INTEM clotting time (CT) with heparinase (HEPTEM) is frequently used to detect residual heparin after cardiopulmonary bypass (CPB) in cardiac surgery. This study investigated whether the HEPTEM CT reflects the presence of residual heparin and the association of the protamine-to-heparin ratio to the INTEM and HEPTEM CT. We retrospectively evaluated thromboelastometry data that were obtained before CPB and after protamine infusion following CPB in two tertiary hospitals. The number of patients with an ⋯ HEPTEM CT ratio > 1.1 was observed in 16 % of the patients prior to CPB, and in 15 % after protamine administration. Interestingly, 23 % and 36 % of the patients had an HEPTEM CT exceeding the INTEM CT before CPB and following protamine administration. The HEPTEM CT was longer than the INTEM CT in patients with a P:H-ratio of 1:1 (265 ± 132 vs 260 ± 246 s; p=0.002) or P:H-ratio of 1.3:1 (357 ± 174 vs 292 ± 95 s; p=0.001). Increasing P:H-ratios induced a prolonged HEPTEM CT in fresh blood. In conclusion, limited agreement was observed between INTEM and HEPTEM clotting time in the absence of heparin. INTEM comparison to HEPTEM may not always reliably reflect the presence of residual heparin, while protamine may additionally affect the latter test. These observations complicate HEPTEM results interpretation in clinical situations with suspected residual heparin effect after protamine.