Thrombosis Journal最新文献

Background: Antithrombin (AT) is a serine protease inhibitor which exerts its anticoagulant effect through binding to serine residues in the active centers of procoagulant serine proteases. Its deficiency is associated with increased risk of venous thrombosis. We aim to investigate the pathogenic mechanism of two natural mutants (W221C and M284R) in inherited AT deficiency.

Methods: We analyzed 9 unrelated patients with inherited AT deficiency by extracting peripheral blood DNA and sequencing the SERPINC1 gene after amplification by polymerase chain reaction. Enzyme-linked immunosorbent assay and heparin affinity chromatography were used to assess AT secretion and purification efficiency. The mutant AT models were evaluated via computational simulations.

Results: Among the 9 patients with inherited AT deficiency, 8 patients had type I AT deficiency, and one patient had type II AT deficiency with subtype of reactive site mutation. Seven of them experienced venous thrombotic events and all patients were found genetic mutations including missense (n = 6), deletion (n = 2) and insertion (n = 1). Two point mutations, W221C and M284R, were identified and were hypothesized to affect AT by destabilizing the central β-sheet. Based on immunoassays and heparin purification, the W221C mutant may impair AT secretion, whereas M284R mutant decreased the total AT production (696.8 ± 151.6 ng/ml versus 3833.72 ± 315.4 ng/ml, p = 0.029). Both mutants delayed the peak of AT release in heparin affinity chromatography.

Conclusions: Our study demonstrates that two mutations in SERPINC1 gene altered the production and structure of AT by in vitro protein expression and functional studies, including protein secretion and production. These findings enhance our understanding of the genetic basis of AT deficiency and its possible clinical implications.

Background: The gut microbiota of venous thromboembolism (VTE) patients exhibited significant alterations. However, the causal relationship between gut microbiota and VTE has not been fully understood. This study aimed to assess the causal relationship between gut microbiota and the risk of VTE using a two-sample Mendelian Randomization (MR) study.

Methods: The gut microbiota and VTE genetic data were collected from the MiBioGen consortium and the UK biobank, respectively. The potential causal relationship between gut microbiota and VTE was investigated using a two-sample MR analysis, including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode methods. Cochran's Q-test, MR-PRESSO, and MR-Egger regression intercept analysis were utilized to perform sensitivity analysis.

Results: At the genus level, the results of MR analysis found that Coprococcus1 (OR: 1.0029, 95% CI: 1.0005-1.0054, p = 0.0202) was suggestively linked with an increased risk of VTE, while Slackia (odds ratio (OR): 0.9977, 95% confidence interval (CI): 0.9957-0.9998, p = 0.0298), Butyricicoccus (OR: 0.9971, 95% CI: 0.9945-0.9997, p = 0.0309), Eubacterium coprostanoligenes group (OR: 0.9972, 95% CI: 0.9946-0.9999, p = 0.0445), and Bacteroides (OR: 0.9964, 95% CI: 0.9932-0.9995, p = 0.0234) were suggestively associated with a reduced risk of VTE. No heterogeneity and horizontal pleiotropy was detected.

Conclusion: This study found that there were potential causal relationships between five gut microbiota and VTE. Our findings may provide new insights into the mechanisms of VTE.

Background: Many studies have indicated that hyperuricemia is positively correlated with secondary deep venous thrombosis (DVT); however, the risk factors for idiopathic DVT based on gender differences, such as serum uric acid (SUA) and hyperuricemia, have not been fully examined.

Objectives: To investigate the association between hyperuricemia and the occurrence of idiopathic lower extremity DVT based on gender differences.

Methods: This was a retrospective analysis of 4299 patients who were hospitalized at the Affiliated Hospital of Qingdao University from January 2012 to October 2021 and who underwent ultrasound of the lower limbs. A total of 930 patients were diagnosed in the DVT group, and 3369 patients were diagnosed in the control group without DVT. The baseline SUA and other important baseline data were compared between the two groups, and sex was stratified. Multivariate logistic regression analysis models adjusted for potential confounders were used to investigate the associations between hyperuricemia and idiopathic lower extremity DVT.

Results: The SUA level in patients with idiopathic DVT was significantly greater than that in patients without DVT (total: 6.00 ± 1.75 vs. 5.40 ± 1.56 mg/dL, respectively; male: 6.42 ± 1.60 vs. 5.87 ± 1.57 mg/dL, respectively; female: 5.58 ± 1.79 vs. 4.72 ± 1.27 mg/dL, respectively; all P < 0.001). The proportion of patients with hyperuricemia in the idiopathic DVT group was significantly greater than that in the control group (total: 29.03% vs. 16.10%, respectively; male: 35.26% vs. 23.19%, respectively; female: 22.73% vs. 5.74%, respectively; all P < 0.001). The incidence of DVT in patients with hyperuricemia was significantly greater than patients with normouricemia (33.29% vs. 18.92%, respectively), and this difference was particularly prominent among women (58.01%). According to the univariate model, hyperuricemia was significantly associated with a grester risk of idiopathic DVT. After adjustment for potential confounders, this association remained significant. The risk of idiopathic lower extremity DVT in patients with hyperuricemia was 2.643-fold greater than that in patients with normouricemia (Model 3: OR: 2.643, 95% CI: 2.165-3.228). After stratification by sex, the risk of idiopathic lower extremity DVT in female patients with hyperuricemia was 7.482-fold greater than that in patients with normouricemia (Model 3, OR: 7.482, 95% CI: 4.999-11.199).

Conclusion: In the Chinese population, hyperuricemia is closely related to an increased risk of idiopathic lower extremity DVT, especially in female patients.

This critique evaluates a retrospective observational study on the impact of extracorporeal membrane oxygenation (ECMO) treatments on acquired von Willebrand syndrome (AVWS) in patients with out-of-hospital cardiac arrest (OHCA). The study is praised for its detailed observational methodology, robust statistical analyses, and comprehensive overview of patient outcomes. These strengths enhance the applicability of the results to real-world clinical practice. However, the study's retrospective design poses inherent risks of bias and confounding factors, which the authors acknowledge but do not extensively address. The absence of a control group of OHCA patients who did not receive ECMO is a significant limitation, as it weakens the ability to isolate the impact of ECMO on AVWS development. Additionally, a more in-depth exploration of the mechanisms by which ECMO contributes to AVWS is needed. Despite these limitations, the study contributes valuable insights into ECMO-related complications and underscores the necessity for vigilant management strategies to mitigate AVWS risks in this high-risk population. The critique concludes by calling for future prospective studies and the development of preventative protocols to improve patient outcomes in ECMO-treated OHCA patients.

Background: The relationship between venous thromboembolism and both insulin resistance and metabolic syndrome is still a matter of debate. The objective of this work was to investigate the possible association between cerebral venous sinus thrombosis (CVST) and both insulin resistance and metabolic syndrome. We aimed also to assess micro-RNA-122 serum levels in patients with CVST in comparison to controls.

Methods: This case-control study was conducted on patients having a clinical and neuroimaging diagnosis of acute CVST (within 1 week from the onset). Patients with inconclusive brain imaging, those with a history of malignancy, diabetic patients, and patients on drugs known to affect the insulin sensitivity or lipid profile were excluded from the study. Metabolic syndrome in the included cases and controls was evaluated by measuring waist circumference and blood pressure in addition to assessment of Triglycerides, HDL, and fasting blood sugar. The state of insulin resistance was established if the Homeostasis model assessment-insulin resistance (HOMA-IR) value > 2.5. Serum micro-RNA-122 serum level was measured for both patients and controls.

Results: In the present study, 36 cases diagnosed as having CVST and 34 age & sex matched controls were included. There were statistically significant differences between patients with CVST and controls regarding BMI, waist circumference, TG, fasting glucose, fasting insulin & HOMA- IR (P-value = 0.002, 0.001, 0.004, 0.003, 0.021, 0.008 respectively). There was no statistically significant difference between patients with CVST and controls regarding micro-RNA-122 serum level (P-value = 0.376), whereas CVST patients with insulin resistance had a significantly higher micro-RNA-122 serum level in comparison to those without (P-value < 0.001). Patients with CVST had a significantly higher frequency of both metabolic syndrome and insulin resistance in comparison to controls (P-value = 0.008, 0.002 respectively).

Conclusion: There is a significant association between CVST and both insulin resistance and metabolic syndrome.

The high incidence of deep vein thrombosis (DVT) in evacuees has been recognized since the 2004 Niigata-Chuetsu Earthquake in Japan. We hypothesized that the number and location of communicating branches of the soleal veins might influence thrombus development and that the median septum of the soleus muscle influences the venous network of the soleal veins. This study aimed to investigate how the network of soleal veins varies with the shape and thickness of the median septum and to elucidate factors predisposing soleal veins to DVT. The lower legs of 30 sides from 15 formalin-preserved cadavers were observed. The central soleal vein, the predilection site for thrombus among the six veins within the soleus muscle, divides into three branches: medial, central, and lateral. The soleus muscle has a unique architecture with converging muscle fibers on the anterior surface of the median septum. We examined the positional relationship between the central soleal vein and the median septum. The median septum morphology was either straight (14 sides, 46.7%) or curved (16 sides, 53.3%). The number of communicating branches was significantly higher in the curved type. The curved type also had a communicating vein penetrating the median septum, with the central branch passing deeper than in the straight type. The median septum could restrict the enlargement of communicating branches, causing thrombosis through disturbance of venous blood flow. Future research will clarify the median septum's influence on the soleal vein, potentially identifying soleus muscles at high risk of developing DVT.

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms.Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1.The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally "skin limited" inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes.

Background: Patients with traumatic pelvic fracture (TPF) are at high risk for developing deep vein thrombosis (DVT). However, there is still no unified standard on how to distinguish high-risk groups for DVT in patients with TPF and how to accurately use anticoagulants at present.

Objectives: This observational study aimed to establish a DVT risk nomogram score (DRNS) model for TPF patients, and to explore the value of the DRNS model as a clinical guideline in the prevention of DVT with low molecular weight heparin (LMWH).

Methods: Independent risk factors of lower extremity DVT were screened through Lasso regression and logistic regression. A DRNS model was established per this.

Results: The independent risk factors of DVT included combined femoral fractures, age ≥ 40 years old, BMI (body mass index) ≥ 24 kg/m², ISS score, fibrinogen concentration, and the minimum concentration of ionized calcium within 48 h after admission. The optimal cutoff value for DRNS was 78.5. In the low-risk population of DVT (DRNS < 78.5), there was no statistical significance of variation about the incidence of DVT progression between the LMWH once a day (qd) group and the LMWH once every 12 h (q12h) group, with P = 0.323. In the high-risk population of DVT (DRNS ≥ 78.5), the incidence of DVT progression in the LMWH qd group was significantly higher than that in the LMWH q12h group, with P = 0.002.

Conclusions: The DRNS model based on independent risk factors of DVT could stratify the risk of DVT for TPF patients, and it was able to provide more precise DVT drug prevention plans for clinicians.

COVID-19 may induce a state of hypercoagulability, particularly in critically ill patients, for reasons that remain unknown. Numerous studies have identified the presence of antiphospholipid antibodies in patients with COVID-19; however, the definitive diagnosis of antiphospholipid syndrome continues to pose challenges. Here, we present the case of a patient infected with SARS-CoV-2 who developed life-threatening severe thrombocytopenia, profound anaemia, acute pulmonary hypertension, right ventricular failure, and renal insufficiency. Laboratory investigations revealed significantly elevated levels of antiphospholipid antibodies. We conducted a one-year follow-up study with blood sampling performed every 12 weeks. The patient exhibited persistent high titres of antiphospholipid antibodies and ongoing renal dysfunction necessitating daily oral warfarin antithrombotic therapy. Antiphospholipid syndrome is a complex clinical condition that poses challenges for clinicians, particularly in critically ill patients, and is often associated with delayed and inaccurate diagnosis and treatment. Therefore, we extensively reviewed the literature and international guidelines to conduct a comprehensive analysis of the aetiology, pathogenesis, and treatment strategies of APS. We hope this work will provide a valuable reference for health care professionals.