Thrombophilia Research Articles

Recurrent thrombotic events in pediatric antiphospholipid syndrome: A systematic review and meta-analysis

BackgroundPediatric antiphospholipid syndrome (APS) is one of the most common acquired hypercoagulable states in children, yet it remains poorly characterized. ObjectivesTo perform a systematic review and meta-analysis of the pooled incidence of thrombotic recurrence in this population (primary outcome), exploring the effect of age, APS type (primary vs. secondary to autoimmune diseases), and type of index thrombotic event. Secondary outcomes included the incidence of bleeding events and mortality. Materials and methodsThe MEDLINE, EMBASE, and COCHRANE databases were searched for studies reporting outcomes of cohorts of children aged ≤18 years with thrombotic APS as defined by the revised Sydney classification criteria. ResultsA total of 1011 studies were identified; of those, 9 were included in the final analysis (352 patients). The pooled incidence proportion of thrombosis recurrence was 0.27 [0.18–0.37], with an overall follow-up duration of a median of 2.7 to 5.8 years or a mean of 2.6 to 6.1 years. The estimate did not change meaningfully according to APS type (0.30 [0.18–0.46] for primary APS vs. 0.29 [0.19–0.42] for autoimmune APS), nor when the index thrombotic event was venous vs. arterial (0.30 [0.20–0.41] vs. 0.27 [0.27–0.51], respectively). The incidence of bleeding events was not reported in these studies. The incidence proportion of mortality was estimated at 0.07 [0.04–0.11] over the follow-up period, with 8/10 of the reported deaths directly associated with recurrent thrombotic events. ConclusionsThe incidence of thrombotic recurrence in children with APS is high and requires attention to evaluate anticoagulation management in this population.

Cerebral venous thrombosis at high altitude: more severe symptoms and specific predisposing factors than plain areas

BackgroundExposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas.MethodsWe retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People’s Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups.ResultsA total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively.ConclusionsThe more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

Impact of thyroid function on coagulation and venous thromboembolism: a two-sample mendelian randomization study.

The association between thyroid function, coagulation and venous thromboembolism (VTE) has been reported in observational studies with conflicting findings. This study aimed to elucidate the causal effects of thyroid function on coagulation and VTE from a genetic perspective. Two sample Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies in a European population. Coagulation status was associated with nine coagulation-related factors (F VIII, F IX, F XI, Fibrinogen, Antithrombin-III, Thrombomodulin, Plasminogen activator inhibitor-1, Protein C and Protein S). Inverse variance weighting with random effect method was used as the main analytic approach with MR-Egger, weighted median, simple mode and weighted mode methods serving as complements. Sensitivity analyses including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis were conducted to further assess the reliability of results. No genetic causal effects of thyroid function on VTE (including pulmonary embolism and deep venous thrombosis) were found. Genetically, hyperthyroidism was suggestively related to decreased Antithrombin-III (β: -0.04 [95% CI: -0.06 to - 0.01], p = 0.010) and Protein C (β: -0.03 [95% CI: -0.06 to 0.00], p = 0.045). No notable associations were observed between other thyroid function parameters and coagulation-related factors. We provide suggestive genetic evidence supporting the causal effect of hyperthyroidism on decreased level of anticoagulant factors including Antithrombin-III and Protein C. However, whether this genetic causality could lead to clinically significant hypercoagulable state and increased risk of VTE in hyperthyroid population needs to be further addressed.

Clinical Significance of Hyperhomocysteinemia in Free Flap Failure: A Case Report

AbstractFailure of a microvascular free flap remains rare, yet multiple failures can occur, particularly in the presence of hypercoagulable conditions. This case series highlights our experience with a rare hypercoagulable state: hyperhomocysteinemia.We present two cases of patients with hyperhomocysteinemia in this report. High-dose heparinization was administered to both patients, resulting in successful salvage of one flap and failure of the other. Notably, one patient had a history of prior free flap failures. However, after correcting hyperhomocysteinemia, subsequent free flaps were successful.In cases of detected complications, a coagulability study is warranted, and adjustments to anticoagulation treatment may be necessary. Furthermore, when a history of flap failures is evident, screening for hyperhomocysteinemia may be warranted, with correction made prior to reconstruction.

An Investigative Study of Prothrombin Time, Activated Partial Thromboplastin Time and Antithrombin Levels in Patients with Ischaemic Stroke

Background: The haemostatic system maintains a balance between prothrombotic and antithrombotic components in the body. The role of this system in ischaemic stroke is not certain. Objective: Prothrombin time (PT) and Activated Partial Thromboplastin Time(APTT) are widely used screening tests to assess the haemostatic cascade. We sought to evaluate the relevance of these test and antithrombin (AT) levels in patients with ischaemic stroke. Methods: AT, platelet count, PT and APTT tests were carried out for 65 patients with ischaemic stroke and 65 controls with no history of stroke. Results: The mean age of stroke subjects was 60.4 ± 12.3yrs. PT and APTT in the test and control groups were similar and Antithrombin levels did not show significant difference. But there was a significant association between functional AT deficiency and diabetes mellitus in the ischaemic stroke group. A significant negative correlation existed between functional AT activity and prothrombin and between AT Ag levels and APTT Conclusion: There was no difference in the Antithrombin levels, PT and APTT values in patients with ischaemic stroke and those without a history of stroke and carrying out these tests routinely to assess hypercoagulable states in ischaemic stroke patients may not have any diagnostic value in our population.

Chronic systemic thrombosis of unknown etiology with concurrent essential thrombocythemia and recurrent stroke: A case report

Here, we report a male patient under hypercoagulable state of unproven etiology, who used to present with recurrent thrombotic episodes since young age after he stopped taking anticoagulant. At the age of 73, he was detected to have essential thrombocythemia while grappling with recurrent strokes. On both occasions, he presented with a basilar thrombus. His National Institutes of Health Stroke Scale (NIHSS) score improved from 18 to 2 on the first occasion and from 17 to 2 sixteen days later on the second occasion. Thrombolysis was done on both occasions, but endovascular therapy was not done on either occasion due to chronicity of the thrombus and remarkably improved NIHSS post-thrombolysis. For patients with recurrent thrombotic events of undetermined etiology, an anticoagulant should be indicated. Repeat thrombolysis can be performed without endovascular therapy within a brief gap of 16 days, even in stroke patients with moderate to high NIHSS.

Abstract We127: Infective Endocarditis in COVID-19 - An Unusual Suspect

Introduction: The COVID-19 pandemic globally overwhelmed healthcare systems and the complications associated with this illness have contributed to poor outcomes. The hypercoagulable state associated with COVID-19 is well recognized in the literature. Thromboembolic complications such as left ventricular thrombus (LVT), deep venous thrombosis (DVT) and pulmonary embolism (PE) have been increasingly reported. Dhakal et al. published an association between COVID-19 and cardiovascular disease, including possible complication by infective endocarditis (IE) which was confirmed by Amir et al. reporting the first case. Since then, there have been few reported cases. We present a case of COVID-19 in a patient who developed LVT, complicated by non-valvular IE by an underreported organism, Granulicatella adiacens. Case Presentation: A 55-year-old male with history of dental caries, provoked DVT/PE, NSTEMI x2 and STEMI in-stent restenosis requiring thrombectomy presented to the hospital with a 2-day history of shortness of breath, fatigue, cough, change in mentation and right-sided weakness. He tested positive for COVID-19 by NAAT. CXR revealed cardiomegaly and multiple bilateral infiltrates. CT head demonstrated acute ischemic stroke of the left occipital, parietal and posterior temporal lobes, also confirmed on MRI. CTA neck showed 30% stenosis of left ICA. Blood cultures x2 resulted positive for G. adiacens. Echocardiogram was obtained, demonstrating reduced EF of 35% and the presence of a large, 2.7 x 2.2cm mobile thrombus in the apical-septal region of the left ventricle, not visualized on previous echocardiogram 6 months earlier. Methods: Data was collected from direct patient care and electronic medical records. Discussion: G. adiacens is a fastidious gram-positive coccus, part of the nutritionally variant streptococci (NVS) species, and part of the normal oral and gastrointestinal flora. It is also found in dental plaques and endodontic abscesses. NVS account for less than 5% of cases of bacteremia and IE. G. adiacens account for even fewer cases. Two separate meta-analyses conducted by Quintero-Martinez et al. and George et al. failed to reveal any cases of IE attributable to G. adiacens in the setting of COVID-19 infection. In conclusion, we believe that the hypercoagulable state of COVID-19 infection led to endocardial damage and development of LVT, thereby creating a nidus for microorganism adherence from underlying dental carries resulting in thromboembolic stroke.

AB037. Association between systemic immune-inflammation index with hypercoagulable state in primary brain tumor: a retrospective study in Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

Hypercoagulable state is considered a common complication in brain tumors, which increases the risk of thromboembolic events, leading to mortality and morbidities. Detecting hypercoagulability typically requires expensive tests, such as D-dimer and fibrinogen, which are not accessible in many healthcare facilities in Indonesia. The systemic immune-inflammation index (SII) is known as an inflammation marker that contributes to hypercoagulability in many conditions. SII tests are more affordable and widely available, but there is still not much study that investigates the association between SII and hypercoagulable state in primary brain tumors. This preliminary study aimed to find an association between SII with hypercoagulable state in primary brain tumor conditions. We collected data from inpatients diagnosed with primary brain tumors from 2021 to 2023 in Dr. Cipto Mangunkusumo Hospital. Hypercoagulable states were established from high D-dimer serum testing (>660 µg/L). SII was calculated by the following formula: neutrophil counts × platelet counts/lymphocyte counts. Both D-dimer and SII were collected at first admission to the hospital. The receiver operating characteristic (ROC) curve were used to determine the SII cut-off value. Bivariate and multivariate logistic analyses were performed to confirm the association with the incidence of hypercoagulable state. This study enrolled 65 patients with primary brain tumors, 73.8% subjects with hypercoagulable state. A total of 61.5% were female, mean age 47.54±2.02 years. High-grade tumors exhibited a higher prevalence than low-grade tumors (53.8% vs. 46.2%). SII cut-off value determined at 1,343.50 (sensitivity 56.9%, specificity 57.1%). We found no significant association between SII and hypercoagulable state. Multivariate analyses show that duration of brain tumor before 6 months (P=0.04), and history of brain tumor surgery (P=0.02) were significantly associated with the incidence of hypercoagulable state in primary brain tumor. Based on the findings in this investigation, we find 73.8% subjects with hypercoagulable states in primary brain tumor. No significant relationship between high SII and hypercoagulable states but significant association of duration brain tumor before 6 months and history of brain tumor surgery with hypercoagulable state in primary brain tumor.

Clinical analysis of seven cases of primary hyperoxaluria type 1

We retrospectively analyzed the clinical data of seven patients (four men and three women) with primary hyperoxaluria (PH) type 1 (PH1) in the Department of Nephrology of Zhongda Hospital, Southeast University from January 2018 to October 2023. The mean age at disease onset was 32.1 (range: 26-42) years. The mean age at diagnosis was 40.6 (range: 28-51) years. All patients initially had kidney stones, and three patients were found to have renal insufficiency at the time of disease onset. Among them, two patients underwent hemodialysis immediately. Symptoms at the first visit included bone pain (n=7), joint pain or deformity (n=5), fatigue (n=5), hypotension (n=3), and subcutaneous nodules (n=2). Four patients had a family history of PH. All patients had varying degrees of anemia (60-114 g/L), significant hypoalbuminemia (16.5-32.1 g/L), and hypercoagulable state (D-dimer: 2 230-12 781 μg/L). Seven patients received maintenance hemodialysis; their mean age was 37.7 (range: 26-50) years. The mean duration from disease onset to hemodialysis was 5.6 (range: 0-20) years. Five patients repeatedly experienced dialysis access dysfunction. Three patients underwent kidney transplantation before a diagnosis was made, and all transplanted kidneys lost function due to oxalate deposition. The mean follow-up duration was 14.43 (range: 4-38) months. Unfortunately, one patient died. All seven patients underwent computed tomography of the abdomen. All patients suffered skeletal abnormalities, bilateral nephrolithiasis, and nephrocalcinosis. Six patients carried AGXT gene mutations, including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included: c.823-824dup.AG (p.S275Rfs*38)(exon 8), c.815-816ins.GA (p.S275Rfs*38)(exon 8), c.595G>A (p.G199S) (exon 5), c.32C>G (p.P11R) (exon 1), and c.638C>T (p.A213V)(exon 6). According to the American College of Medical Genetics and Genomics guidelines, two loci were identified as likely pathogenic variants, seven were identified as pathogenic variants, and one locus was identified as having uncertain significance. In addition, patients 1 and 4 underwent skin biopsy, patient 2 underwent renal transplant biopsy, and patient 3 underwent bone marrow biopsy. Interestingly, significant oxalate deposition was found in the tissues. Therefore, PH1 is a rare autosomal recessive inherited disease. This study not only enhanced the understanding of the clinical characteristics of PH1 patients but also had great significance in early diagnosis and treatment of the disease.

Social disparities in pulmonary embolism and deep vein thrombosis during the coronavirus disease 2019 pandemic from the Nationwide inpatient Sample

ObjectivesStudies have shown that coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Studies have yet to examine the interconnectedness between COVID-19, hypercoagulability, and socioeconomics. The aim of this work was to investigate socioeconomic factors that may be associated with pulmonary embolism (PE), deep vein thrombosis (DVT), and COVID-19 in the United States. MethodsWe performed a 1-year (2020) analysis of the National Inpatient Sample database. We identified all adult patients diagnosed with COVID-19, acute PE, or acute DVT using unweighted samples. We calculated the correlation and odds ratio (OR) between COVID-19 and (1) PE and (2) DVT. We executed a univariate analysis followed by a multivariate analysis to examine the effect of different factors on PE and DVT during the COVID-19 pandemic. ResultsWe identified 322,319 patients with COVID-19; 78,101 and 67,826 patients were identified with PE and DVT, respectively. PE and DVT, as well as inpatient mortality associated with both conditions, are significantly correlated with COVID-19. The OR between COVID-19 and PE was 2.04, while the OR between COVID-19 and DVT was 1.44. Using multivariate analysis, COVID-19 was associated with a higher incidence of PE (coefficient, 2.05) and DVT (coefficient, 1.42). Other factors that were significantly associated (P < .001) with increased incidence of PE and DVT along with their coefficients, respectively, include Black race (95% confidence interval [CI], 1.23-1.14), top quartile income (95% CI, 1.08-1.16), west region (95% CI, 1.10-1.04), urban teaching facilities (95% CI, 1.09-1.63), large bed size hospitals (95% CI, 1.08-1.29), insufficient insurance (95% CI, 1.88-2.19), hypertension (95% CI, 1.24-1.32), and obesity (95% CI, 1.41-1.25). Factors that were significantly associated (P < .001) with decreased incidence of PE and DVT along with their coefficients, respectively, include Asians/Pacific Islanders (95% CI, 0.52-0.53), female sex (95% CI, 0.79-0.74), homelessness (95% CI, 0.62-0.61), and diabetes mellitus (0.77-0.90). ConclusionsIn the Nationwide Inpatient Sample, COVID-19 is correlated positively with venous thromboembolism, including its subtypes, PE and DVT. Using a multivariate analysis, Black race, male sex, top quartile income, west region, urban teaching facilities, large bed size hospitals, and insufficient social insurance were associated significantly with an increased incidence of PE and DVT. Asians/Pacific Islanders, female sex, homelessness, and diabetes mellitus were significantly associated decreased incidence of PE and DVT.

Posterior Circulation Ischemic Stroke Is Associated with More Severe Forward Head Posture in Patients with Cervicalgia

Chronic risk factors of posterior circulation ischemic strokes remain unknown. There is, however, evidence that anatomical variations within the vertebrobasilar system could potentially lead to the development of posterior circulation strokes. We investigated the association of forward head posturing (FHP), a chronic anatomical change seen in patients with cervicalgia, with posterior circulation strokes. In this case-control study, we identified adult patients diagnosed with cervicalgia and ischemic posterior circulation infarcts from 2007 to 2023. Cases were paired with controls with cervicalgia without posterior circulation stroke and matched for known risk factors. C0-C2 angle, C2-C7 angle, and sagittal vertical axis shift were measured as metrics for FHP severity on lateral cervical spine x-rays. Paired t tests were applied to compare stroke risk factors and FHP between groups. Participants included 206 patients (103 cases and 103 controls) with a mean age of 64.4 years; 51.5% were female. There were no statistically significant differences between risk factors for stroke, including hypertension, hyperlipidemia, diabetes, smoking, hypercoagulable state, and atrial fibrillation. There were statistically significant differences in C0-C2 angle (30.7° vs. 23.2°, P=0.002) and sagittal vertical axis shift (35.4 mm vs. 25.3 mm, P < 0.001). This case-control matched-pair study found that in adults with cervicalgia, posterior circulation ischemic stroke was associated with more severe FHP as noted in C0-C2 angle and sagittal vertical axis shift measurements. Further, this association may be due to chronic changes in circulation flow dynamics within the vertebrobasilar system with the postural change.

Hypercoagulable state and effect of low-molecular-weight heparin prophylaxis on coagulation after lung cancer resection: results from thrombo-elastography.

Lung cancer patients undergoing surgery are at increased risk for Venous thromboembolism (VTE). We monitored changes in perioperative coagulation status through Thrombo-elastography (TEG), and monitored the anticoagulant effect of low molecular weight heparin through TEG for the first time. From July 2019 to January 2020, 207 patients receiving curative surgery were retrospectively screened. and 23 patients were excluded because they did not meet the inclusion criteria. Blood samples were required at three time points (prior to, the first and third day after surgery). Some patients were administrated nadroparin calcium daily from the first day after surgery. Repeated measures ANOVA and Chi-square test were used to analyze the coagulation states variation. To balance the confounders, propensity score matching (PSM) was used to determine the differences of coagulation states between patients with or without Low-molecular-weight heparin (LMWH) prophylaxis. In 184 patients, TEG parameters displayed significant procoagulant changes after lung surgery but conventional coagulation tests exhibited paradoxical trends. There were 6.5% (12/184) of patients identified as hypercoagulability before surgery. According to TEG results, the proportion of patients with hypercoagulability rose from 21.7% to 25% postoperatively, but more were classified into platelet or mixed hypercoagulability at third day compared with that at first day (3.8% vs 14.1%, P < 0.001). By PSM analysis, there were no significant differences in the proportion of hypercoagulable patients postoperatively between chemoprophylactic and nonprophylactic group. TEG was eligible to distinguish changing states of hypercoagulability postoperatively and indicate the role of platelet in blood hypercoagulability. Administration of postoperative LMWH prophylaxis showed little mitigation on hypercoagulable states.

Circadian misalignment disrupts biomarkers of cardiovascular disease risk and promotes a hypercoagulable state.

The circadian system regulates 24-h time-of-day patterns of cardiovascular physiology, with circadian misalignment resulting in adverse cardiovascular risk. Although many proteins in the coagulation-fibrinolysis axis show 24-h time-of-day patterns, it is not understood if these temporal patterns are regulated by circadian or behavioral (e.g., sleep and food intake) cycles, or how circadian misalignment influences these patterns. Thus, we utilized a night shiftwork protocol to analyze circadian versus behavioral cycle regulation of 238 plasma proteins linked to cardiovascular physiology. Six healthy men aged 26.2±5.6 years (mean ± SD) completed the protocol involving two baseline days with 8-h nighttime sleep opportunities (circadian alignment), a transition to shiftwork day, followed by 2days of simulated night shiftwork with 8-h daytime sleep opportunities (circadian misalignment). Plasma was collected for proteomics every 4h across 24 h during baseline and during daytime sleep and the second night shift. Cosinor analyses identified proteins with circadian or behavioral cycle-regulated 24-h time-of-day patterns. Five proteins were circadian regulated (plasminogen activator inhibitor-1, angiopoietin-2, insulin-like growth factor binding protein-4, follistatin-related protein-3, and endoplasmic reticulum resident protein-29). No cardiovascular-related proteins showed regulation by behavioral cycles. Within the coagulation pathway, circadian misalignment decreased tissue factor pathway inhibitor, increased tissue factor, and induced a 24-h time-of-day pattern in coagulation factor VII (all FDR <0.10). Such changes in protein abundance are consistent with changes observed in hypercoagulable states. Our analyses identify circadian regulation of proteins involved in cardiovascular physiology and indicate that acute circadian misalignment could promote a hypercoagulable state, possibly contributing to elevated cardiovascular disease risk among shift workers.

Morvan's syndrome with hypercoagulable condition in a patient positive for anti-CASPR2 antibodies: A case report.

The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan's syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2). A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable. The patient was diagnosed as Morvan's syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state. Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy. The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge. Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan's syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan's syndrome and exhibiting positivity for anti-CASPR2 antibodies.

Mechanisms and management of thrombosis in cancer: focus on gastrointestinal malignancies.

Cancer patients have an increased risk of venous thromboembolism (VTE) which is their second cause of death after disease progression itself. Several thrombotic risk factors coexist in cancer patients, including the ability of both cancer and tumoral microenvironment's cells to directly or indirectly activate platelets and the enzymes of the coagulation cascade, resulting in a hyper-coagulable state of blood. This narrative review gives an overview of the main mechanisms leading to VTE in cancer patients, including the role that platelets and the clotting proteins may have in tumor growth and metastasis. Noteworthy, the haemostatic balance is altered in cancer patients who may, next to a thrombosis tendency, also have an increased risk of bleeding. To highlight the complexity and the precariousness of the haemostatic balance of these patients, we discuss two specific gastrointestinal malignancies: hepatocellular carcinoma, which is frequently associated with liver cirrhosis, a condition that causes profound alterations of haemostasis, and colorectal cancer, which is characterized by a fragile mucosa that is prone to bleeding. Understanding the molecular mechanisms of cancer-associated thrombosis may give a unique opportunity to develop new innovative drugs, acting differently on distinct pathways and potentially allowing to reduce the risk of bleeding related to antithrombotic therapies. Significance Statement The topic is significant because understanding the molecular mechanisms leading to cancer associated thrombosis and bleeding, focusing on gastrointestinal malignancies, enables the development of more rationale and innovative antithrombotic strategies for cancer associated thrombosis. Eventually, this will support an improved and patient-tailored antithrombotic management in vulnerable oncologic patients.

Early Online.

Long-haul flights have been associated with a two- to four-fold increased risk of aviation-related thrombosis (ART). Several studies have investigated the extent to which hypoxic hypobaric exposure, dehydration and prolonged immobilisation during air travel induce changes in haemostasis. To investigate the role of high altitude as a risk factor for ART. Healthy volunteers aged ≥18 years (N=40), without risk factors for venous thromboembolism, were exposed to an exacerbated altitude of 18 000 feet (5 486 m) for 1 hour. During the flight, the oxygen (O2) levels of the participants, who received supplemental O2, were measured by pulse oximetry and maintained at >92%. Venous blood and urine samples were collected prior to departure and immediately after flying in an unpressurised twin-engine airplane. D-dimer levels, thromboelastography (TEG) parameters, von Willebrand factor (VWF) activity and urine osmolality were measured. The participants were 19 men and 21 women, with a mean (standard deviation) age of 46 (14) years. A significant difference in D-dimer levels, VWF activity, urine osmolality and TEG parameters (reaction (R) time, kinetic (K) time and maximum amplitude (MA)) before and after the 1-hour flight was observed (p<0.001). Urine osmolality correlated positively with VWF activity levels (r=0.469; p<0.002). Air travel at high altitude induced a hypercoagulable state in healthy volunteers. Future research should focus on whether thromboprophylaxis can significantly obviate the activation of coagulation in response to high altitude.

Antiphospholipid Syndrome: Insights into Molecular Mechanisms and Clinical Manifestations.

Antiphospholipid syndrome (APS) is a complex systemic autoimmune disorder characterized by a hypercoagulable state, leading to severe vascular thrombosis and obstetric complications. The 2023 ACR/EULAR guidelines have revolutionized the classification and understanding of APS, introducing broader diagnostic criteria that encompass previously overlooked cardiac, renal, and hematologic manifestations. Despite these advancements, diagnosing APS remains particularly challenging in seronegative patients, where traditional tests fail, yet clinical symptoms persist. Emerging non-criteria antiphospholipid antibodies offer promising new diagnostic and management avenues for these patients. Managing APS involves a strategic balance of cardiovascular risk mitigation and long-term anticoagulation therapy, though the use of direct oral anticoagulants remains contentious due to varying efficacy and safety profiles. This article delves into the intricate pathogenesis of APS, explores the latest classification criteria, and evaluates cutting-edge diagnostic tools and therapeutic strategies.

Assessment of Coagulation Factors in Patients with Severe Rheumatic Mitral Stenosis in Sinus Rhythm with Left Atrial Appendage Inactivity

BackgroundPatients with severe mitral stenosis (MS) in normal sinus rhythm (NSR), presenting with left atrial appendage (LAA) inactivity and associated left atrial spontaneous echo contrast (LASEC) are prone to left atrium (LA) or LAA thrombus formation. But unlike for atrial fibrillation, oral anticoagulants are not commonly prescribed for this patient subset. This study aimed to compare the levels of procoagulants and fibrinogen in both local (LA) and systemic contexts between patients with severe MS in NSR vs those in healthy control subjects. MethodsThe study involved 35 patients with severe MS in NSR with LAA inactivity and LASEC who were eligible for balloon mitral valvuloplasty vs 35 healthy controls. All patients underwent transthoracic and transesophageal echocardiography to assess MS severity, LAA activity, and LASEC grade, and had blood samples analyzed for procoagulant levels. ResultsResults showed comparable baseline characteristics between groups, with most patients in the New York Heart Association II or III functional classes, and with varying LASEC grades. Patients exhibited significantly higher levels of prothrombin fragment 1 + 2 [patient vs control, 9017 pg/mL (6228.0-10,963.5) vs 1790 pg/mL (842.3-2712), P < 0.0001], thrombin-antithrombin III [patient vs control, 39 ng/mL (5.45-74.85) vs 2.80 ng/mL (1.6-6.5), P < 0.0001], plasminogen activator inhibitor-1 (patients vs controls, 26.09 ± 8.18 ng/mL vs 8.05 ± 3.53 ng/mL, P < 0.0001), and fibrinogen (3.48 ± 0.89 g/L vs 3.01 ± 0.53 g/L, P = 0.029) in the LA of patients, compared to those in control subjects. Systemic procoagulant levels also were elevated in patients, but D-dimer levels were similar between the 2 groups. ConclusionsThe findings suggest a hypercoagulable state in patients, similar to that in patients with atrial fibrillation. The study advocates for consideration of use of oral anticoagulants in these patients until LA and LAA function improves, to mitigate thrombus formation.

Thrombotic Long-Term Consequences of SARS-CoV-2 Infection in Patients with Compensated Cirrhosis: A Propensity Score-Matched Analysis of a U.S. Database.

Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2's impact on hemostasis in compensated patients with cirrhosis. We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients' baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years.

Caffeic acid and its derivative caffeic acid phenethyl ester as potential therapeutic compounds for cardiovascular diseases: A systematic review.

Cardiovascular diseases (CVDs) contribute to major public health issues. Some studies have found that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) may effectively prevent or treat CVDs. However, there is a major need to sum up our current understanding of the possible beneficial or detrimental effects of CA and CAPE on CVDs and related mechanisms. Therefore, this study aimed to summarize the data on this topic. A methodical search was carried out on key databases, including Pubmed, Google Scholar, Scopus, and Web of Science, from the beginning to June 2024. Studies were then assessed for eligibility based on inclusion and exclusion criteria. Treatment with CA and CAPE significantly and positively affected cardiovascular health in various aspects, including atherosclerotic diseases, myocardial infarction, hypertension, cardiac arrhythmias, and hypercoagulation state. Several mechanisms were proposed to mediate these effects, including transcription factors and signaling pathways associated with antioxidant, cytostatic, and anti-inflammatory processes. CA and CAPE were found to have several beneficial effects via multiple mechanisms during the prevention and treatment of various CVDs. However, these promising effects were only reported through in vitro and animal studies, which reinforces the need for further evaluation of these effects via human clinical investigations.