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Aims Further decompensation events markedly increase mortality in patients with decompensated cirrhosis. The coagulation factor VIII/protein C (FVIII/PC) ratio, previously considered as an indicator of thromboembolic events, has recently been recognized as an important prognostic factor in cirrhosis. This study aimed to identify risk factors for predicting further decompensation and to evaluate the predictive value of the FVIII/PC ratio in patients with decompensated cirrhosis. Methods A total of 227 patients were enrolled between January 2020 and December 2021, and followed until June 30, 2023, or until the occurrence of further decompensation. Fine‐Gray competing risk models and the Shapley additive explanations method were used to identify significant predictors of 1‐year further decompensation. The predictive performance of the FVIII/PC ratio was assessed using time‐dependent receiver operating characteristic curves (ROC) and Kaplan–Meier analysis. Results During follow‐up, 62 patients (27.3%) experienced further decompensating events. A high FVIII/PC ratio and an elevated model for end‐stage liver disease score were identified as independent risk factors for further decompensation. The FVIII/PC ratio showed superior predictive performance within 1 year, with an area under the curve of 0.717. Patients were categorized into low (n = 126) and high FVIII/PC (n = 101) groups using the optimal cutoff value (2.86) derived from time‐dependent ROC analysis. Kaplan–Meier analysis demonstrated that patients with a high FVIII/PC ratio had a significantly greater risk of further decompensation (high vs. low FVIII/PC groups: 16.2% vs. 3.3%, p = 0.001), including variceal hemorrhage (high vs. low FVIII/PC groups: 8.9% vs. 1.7%, p = 0.017), jaundice (high vs. low FVIII/PC groups: 8.0% vs. 1.7%, p = 0.031), and recurrent ascites (high vs. low FVIII/PC groups: 16.2% vs. 4.8%, p = 0.010). In contrast, neither the FVIII/PC ratio (high vs. low FVIII/PC groups: 10.7% vs. 9.2%, p = 0.670) nor PC levels (high vs. low PC groups in those without portal vein thrombosis (PVT) at baseline: 7.1% vs. 14.0%, p = 0.200) predicted PVT, while FVIII levels alone remained significant (high vs. low FVIII groups in those without PVT at baseline: 17.9% vs. 6.1%, p = 0.029). Conclusion An increased FVIII/PC ratio is a key predictor of higher risk for further decompensation in patients with decompensated cirrhosis. The activity of FVIII, rather than the FVIII/PC ratio, is recommended for evaluating and predicting the occurrence of PVT. Summary Elevated coagulation factor VIII/protein C (FVIII/PC) ratio predicted increased risk of further decompensation in cirrhotic patients with variceal bleeding. Elevated FVIII/PC ratio is linked to severe liver dysfunction and higher portal pressure. Elevated FVIII/PC ratio does not demonstrate a correlation with portal vein thrombosis; whereas FVIII may serve as a significant predictor of portal vein thrombosis in cirrhosis independently. Cirrhosis is a major global health burden, the progression to further decompensation is associated with significantly increased mortality. However, the specific predictors of further decompensation in cirrhotic patients remain underexplored. The FVIII/PC ratio has emerged as a significant prognostic marker beyond merely reflecting hypercoagulability in liver disease. Our study found that an elevated FVIII/PC ratio could predict further decompensation while FVIII activity alone serves as an independent predictor for portal vein thrombosis.

It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis.

Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients.

We have previously demonstrated that platelet-poor plasma (PPP) obtained from patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state and contains hyperactivated platelets and considerable numbers of already-formed amyloid fibrin(ogen) or fibrinaloid microclots. Due to the substantial overlap in symptoms and etiology between Long COVID/PASC and ME/CFS, we investigated whether coagulopathies reflected in Long COVID/PASC—hypercoagulability, platelet hyperactivation, and fibrinaloid microclot formation—were present in individuals with ME/CFS and gender- and age-matched healthy controls. ME/CFS samples showed significant hypercoagulability as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated PPP from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed hyperactivation of platelets in ME/CFS hematocrit samples. Using a quantitative scoring system, the ME/CFS platelets were found to have a mean spreading score of 2.72 ± 1.24 vs. 1.00 (activation with pseudopodia formation) for healthy controls. We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, the fibrinaloid microclot load was not as great as was previously noted in Long COVID/PASC. Fibrinaloid microclots, in particular, may contribute to many ME/CFS symptoms, such as fatigue, seen in patients with ME/CFS, via the (temporary) blockage of microcapillaries and hence ischemia. Furthermore, fibrinaloid microclots might damage the endothelium. The discovery of these biomarkers represents an important development in ME/CFS research. It also points to possible uses for treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation.

Background The hypercoagulable state associated with pancreatic adenocarcinoma (PDA) results in increased risk of venous thromboembolism, leading to substantial morbidity and mortality. Recently, neutrophil extracellular traps (NETs), whereby activated neutrophils release their intracellular contents containing DNA, histones, tissue factor, high mobility group box 1 (HMGB1) and other components have been implicated in PDA and in cancer-associated thrombosis. Methods Utilizing an orthotopic murine PDA model in C57/Bl6 mice and patient correlative samples, we studied the role of NETs in PDA hypercoagulability and targeted this pathway through treatment with the NET inhibitor chloroquine. PAD4 and RAGE knockout mice, deficient in NET formation, were used to study the role of NETs in platelet aggregation, release of tissue factor and hypercoagulability. Platelet aggregation was assessed using collagen-activated impedance aggregometry. Levels of circulating tissue factor, the initiator of extrinsic coagulation, were measured using ELISA. Thromboelastograms (TEGs) were performed to assess hypercoagulability and changes associated with treatment. Correlative data and samples from a randomized clinical trial of preoperative gemcitabine/nab-paclitaxel with and without hydroxychloroquine were studied and the impact of treatment on venous thromboembolism (VTE) rate was evaluated. Results The addition of NETs to whole blood stimulated platelet activation and aggregation. DNA and the receptor for advanced glycation end products (RAGE) were necessary for induction of NET associated platelet aggregation. PAD4 knockout tumor-burdened mice, unable to form NETs, had decreased aggregation and decreased circulating tissue factor. The NET inhibitor chloroquine reduces platelet aggregation, reduces circulating tissue factor and decreases hypercoagulability on TEG. Review of correlative data from patients treated on a randomized protocol of preoperative chemotherapy with and without hydroxychloroquine demonstrated a reduction in peri-operative VTE rate from 30 to 9.1% with hydroxychloroquine that neared statistical significance ( p  = 0.053) despite the trial not being designed to study VTE. Conclusion NETs promote hypercoagulability in murine PDA through stimulation of platelets and release of tissue factor. Chloroquine inhibits NETs and diminishes hypercoagulability. These findings support clinical study of chloroquine to lower rates of venous thromboembolism in patients with cancer. Trial registration This study reports correlative data from two clinical trials that registered with clinicaltrials.gov, NCT01128296 (May 21, 2010) and NCT01978184 (November 7, 2013).

During the coronavirus disease 2019 (COVID-19) pandemic, some patients with severe COVID-19 exhibited complications such as acute ischemic stroke (AIS), which was closely associated with a poor prognosis. These patients often had an abnormal coagulation, namely, elevated levels of D-dimer and fibrinogen, and a low platelet count. Certain studies have suggested that COVID-19 induces AIS by promoting hypercoagulability. Nevertheless, the exact mechanisms through which COVID-19 leads to a hypercoagulable state in infected patients remain unclear. Understanding the underlying mechanisms of hypercoagulability is of utmost importance for the effective treatment of these patients. The present review aims to summarize the current status of research on COVID-19, hypercoagulability and ischemic stroke. The present review also aimed to shed light into the underlying mechanisms through which COVID-19 induces hypercoagulability, and to provide therapies for different mechanisms for the more effective treatment of patients with COVID-19 with ischemic stroke and prevent AIS during the COVID-19 pandemic.

BackgroundTrousseau syndrome is a cancer-associated hypercoagulable state characterized by recurrent thromboembolic events, including ischemic stroke. Optimal anticoagulation strategies remain controversial, particularly regarding the effectiveness of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin (LMWH).Case presentationWe report two patients with Trousseau syndrome who presented with recurrent multi-territory cerebral infarctions despite ongoing DOAC therapy. Case 1 was a 66-year-old man with active intrahepatic cholangiocarcinoma who developed repeated ischemic strokes and deep vein thrombosis while receiving rivaroxaban. After switching to LMWH, D-dimer levels decreased markedly. However, anticoagulation was de-escalated in the context of apparent normalization of D-dimer, followed by recurrent stroke, subsequent discontinuation of anticoagulation, and a rapid surge in D-dimer levels, ultimately resulting in death. Case 2 was a 74-year-old man with suspected recurrent metastatic gastric adenocarcinoma who developed ischemic stroke while on rivaroxaban. Following transition to LMWH, D-dimer levels progressively declined, and the patient remained clinically stable without recurrence during follow-up. A longitudinal timeline analysis integrating biomarker dynamics, treatment transitions, and clinical events demonstrated distinct patterns between the two cases, suggesting a potential discordance between D-dimer levels and underlying hypercoagulable activity.ConclusionThese cases highlight the dynamic nature of hypercoagulability in Trousseau syndrome. Normalization of D-dimer alone may not reliably indicate sustained control of malignancy-associated hypercoagulability and should not be used in isolation to guide anticoagulation de-escalation. LMWH may provide more consistent control in selected high-risk patients, although causal inference cannot be established from this report.

Estrogen-containing medication, prescribed either for contraception in women of reproductive age or for prevention of cardiovascular events and osteoporosis as well as for alleviation of symptoms related to menopause, is associated with changes in the hemostatic balance and contributes to increased risk of development of venous thromboembolic complications. This risk is dose and medication dependent, increases with age, congenital and/or acquired predisposition to thrombosis, and mode of administration. This review attempts to summarize the current knowledge regarding the pathophysiology of oral contraceptive (OC) and hormone replacement therapy (HRT) -induced prothrombotic state in women, the risk of thrombosis associated with administration of various commercially available OCs and HRT, the additional risk in women with hereditary or acquired thrombophilia, and the currently available recommendations regarding massive screening of women for thrombophilia prior to initial prescription or continuation of treatment with OCs and HRT preparations.

[This corrects the article DOI: 10.3389/fmed.2025.1650001.].

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) ( p  < 0.05); however, the OR for hepatic fibrosis was not statistically significant ( p  > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.