Thrombosis and haemostasis最新文献

Background:  Complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with in-hospital mortality. Asian patients on extracorporeal membrane oxygenation (ECMO) have higher risks of bleeding and in-hospital mortality than Caucasian patients. This study aimed to characterize and identify bleeding complications and their associated factors related to in-hospital mortality in patients with severe coronavirus disease 2019 (COVID-19) requiring VV-ECMO in Japan.

Methods:  In this retrospective observational analysis, the prospective nationwide multicenter registry was used to track real-time information from intensive care units throughout Japan during the COVID-19 pandemic. VV-ECMO patients' registry data between February 1, 2020 and October 31, 2022 were used.

Results:  This study included 441 patients; 178 (40%) had bleeding complications in the following sites: 20% at the cannulation site, 16% in the gastrointestinal tract, 16% in the ear-nose-throat, 13% at the tracheostomy site, 9% intrathoracic, 6% intracranial, and 5% in the iliopsoas. Anticoagulation was discontinued in >50% of patients with intracranial, iliopsoas, and gastrointestinal tract bleeding. ECMO was discontinued in one-third of patients with intracranial, intramuscular, and iliopsoas hemorrhages. Multivariable logistic regression analysis revealed that only gastrointestinal tract bleeding was associated with in-hospital mortality (odds ratio: 2.49; 95% confidence interval: 1.11-5.60; p = 0.03).

Conclusion:  Incidence of bleeding complications was 40% in the Japanese population. Gastrointestinal tract bleeding emerged as a significant predictor of adverse outcomes, necessitating further research into preventive strategies and optimized care protocols. These findings can guide the management of VV-ECMO patients with COVID-19.

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Profound and transient thrombocytopenia of functional platelets without bleeding was observed in patients envenomed by Vipera a. ammodytes (Vaa). This condition was rapidly reversed by administration of F(ab)₂ fragments of immunoglobulin G targeting the whole venom, leaving platelets fully functional. To investigate the potential role of snake venom C-type lectin-like proteins (snaclecs) in this process, Vaa-snaclecs were isolated from the crude venom using different liquid chromatographies. The purity of the isolated proteins was confirmed by Edman sequencing and mass spectrometry. The antithrombotic effect was investigated by platelet agglutination and aggregation assays and blood coagulation tests. Using flow cytometry, the platelet activation and binding of Vaa-snaclecs to various platelet receptors was analyzed. Antithrombotic efficacy was tested in vivo using a mouse model of vascular injury. Two Vaa-snaclecs were purified from the venom. One of them, Vaa-snaclec-3/2, inhibited ristocetin-induced platelet agglutination. It is a covalent heterodimer of Vaa-snaclec-3 (α-subunit) and Vaa-snaclec-2 (β-subunit). Our results suggest that Vaa-snaclec-3/2 induces platelet agglutination and consequently thrombocytopenia by binding to the platelet receptor glycoprotein Ib. Essentially, no platelet activation was observed in this process. In vivo, Vaa-snaclec-3/2 was able to protect the mouse from ferric chloride-induced carotid artery thrombosis, revealing its applicative potential in interventional angiology and cardiology.

Background:  Oral anticoagulation (OAC) following catheter ablation (CA) of nonvalvular atrial fibrillation (NVAF) is essential for the prevention of thrombosis events. Inappropriate application of OACs does not benefit stroke prevention but may be associated with a higher risk of bleeding. Therefore, this study aims to develop clinical data-driven machine learning (ML) methods to predict the risk of thrombosis and bleeding to establish more precise anticoagulation strategies for patients with NVAF.

Methods:  Patients with NVAF who underwent CA therapy were enrolled from Southwest Hospital from 2015 to 2023. This study compared eight ML algorithms to evaluate the predictive power for both thrombosis and bleeding. Model interpretations were recognized by feature importance and SHapley Additive exPlanations methods. With potential essential risk factors, simplified ML models were proposed to improve the feasibility of the tool.

Results:  A total of 1,055 participants were recruited, including 105 patients with thrombosis and 252 patients with bleeding. The models based on XGBoost achieved the best performance with accuracies of 0.740 and 0.781 for thrombosis and bleeding, respectively. Age, BNP, and the duration of heparin are closely related to the high risk of thrombosis, whereas the anticoagulation strategy, BNP, and lipids play a crucial role in the occurrence of bleeding. The optimized models enrolling crucial risk factors, RF-T for thrombosis and Xw-B for bleeding, achieved the best recalls of 0.774 and 0.780, respectively.

Conclusion:  The optimized models will have a great application potential in predicting thrombosis and bleeding among patients with NVAF and will form the basis for future score scales.

Background:  Protein C (PC) deficiency is a well-established risk factor for thromboembolism (TE), commonly manifesting in pediatric patients. This study aimed to elucidate the pathogenic mechanisms of two novel PC mutations, C238G and R189W, identified in Thai children with both venous and arterial TE.

Material and methods:  The effects of wild-type (WT), C238G, and R189W PC variants were investigated through transient transfection of HEK293T cells. PC secretion levels were measured, and immunofluorescence analysis was performed to assess intracellular localization. ER stress-related gene expression and UPR activation were evaluated. Structural analysis was conducted to explore the significance of the C238 and R189W residue in PC functionality.

Results:  The C238G mutation led to a severe 95% reduction in PC secretion, while R189W showed a 30% decrease compared with WT. Immunofluorescence revealed that C238G-PC was predominantly retained in the ER, indicating protein misfolding. C238G-expressing cells exhibited significant upregulation of ER stress-related genes and UPR activation. In contrast, R189W resulted in only a modest increase in UPR gene expression, suggesting a less pronounced impact on protein folding and secretion. Structural analysis demonstrated the critical role of the C238 residue in maintaining PC's disulfide bond and overall conformation.

Conclusion:  This study reveals distinct molecular mechanisms by which the C238G and R189W mutations contribute to PC deficiency and increased thrombotic risk. The findings emphasize the essential role of the C238 residue in preserving PC structure and secretion, enhancing the understanding of PC deficiency-associated TE in pediatric patients.

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.

Objective:  To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada. Individuals being newly prescribed an OC with or without an endometriosis and no VTE history.

Methods:  Detailed information was captured using self-administered questionnaires at baseline and every 6 to 12 months thereafter. Self-reported VTEs were medically validated and reviewed by an independent adjudication committee. Incidence rates (IRs) were calculated per 10,000 woman-years. The association of endometriosis on VTE was determined in a time-to-event analysis, calculating crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) using stabilized inverse probability of treatment weighting (IPTW).

Results:  A total of 22,072 women had an endometriosis diagnosis, and 91,056 women did not. Women with endometriosis contributed 78,751 woman-years during which 41 VTE events occurred (IR: 5.2/10,000, 95% CI: 3.7-7.1) compared to 127 VTEs during 310,501 woman-years in women without endometriosis (IR: 4.1/10,000, 95% CI: 3.4-4.9). The hazard ratio of VTE in women with endometriosis was 1.79 (95% CI: 1.24-2.57) using stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses showed similar results.

Conclusion:  These results highlight the importance of considering endometriosis as a potential factor contributing to VTE in women using OC; however, further research on the relationship between endometriosis and VTE is warranted.

Background Transcatheter mitral valve repair is performed in a patient population at risk for thrombotic and bleeding events. The effects on platelet function and reactivity and their association with bleeding events after mitral transcatheter edge-to-edge therapy (M-TEER) have not been systematically examined.

Objectives We sought to investigate the association of different parameters of platelet function and thrombogenicity with bleeding events post M-TEER.

Methods In this single-center study, 100 consecutive patients with mitral regurgitation receiving TEER were analyzed. Blood was taken directly from the guide-catheter in the left atrium before and after placing the device. Blood samples were analyzed using impedance aggregometry (Multiplate) and TEG6s. The results were compared pre- and postprocedural. The primary outcome was any bleeding complication according to the Bleeding Academic Research Consortium classification within 6 months.

Results A total of 41 patients experienced bleeding events. TEG analysis showed a significant decrease in ADP aggregation and increase in ADP inhibition. In ROC-analysis, TEG ADP aggregation and inhibition and Multiplate ADP aggregation showed moderate predictive values for bleeding events. The delta-ADP-Test (Multiplate) showed the strongest prediction of bleeding (area under the curve: 0.69). Adding platelet function and TEG markers to a model of clinical bleeding risk factors improved the prediction for bleeding events.

Conclusion This study indicates that thrombogenicity might be affected immediately after M-TEER probably due to changes in flow conditions. In particular, platelet aggregation involving the ADP receptor pathway significantly correlated with postprocedural bleeding events. Whether these results could guide peri-interventional antithrombotic therapy and improve peri- and postprocedural outcome requires further investigation.