Thrombophilia Research Articles

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.

Exploring the mechanism of IgA vasculitis pathogenesis through the interaction of thrombin and inflammatory factors using urinary proteomics

To explore the evidence, urinary biomarkers, and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis (IgAV). Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry, followed by Reactome pathway analysis. Protein-protein interaction (PPI) network analysis was conducted using STRING and Cytoscape software. In the validation cohort, 15 healthy children and 25 children with IgAV were included, and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay. A total of 772 differential proteins were identified between the IgAV group and the control group, with 768 upregulated and 4 downregulated. Reactome pathway enrichment results showed that neutrophil degranulation, platelet activation, and hemostasis pathways were involved in the pathogenesis of IgAV. Among the differential proteins, macrophage migration inhibitory factor (MIF) played a significant role in neutrophil degranulation and hemostasis, while thrombin was a key protein in platelet activation and hemostasis pathways. PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses, and these interactions involved MIF. Validation results showed that compared to healthy children, children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels (P<0.05). Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors. Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation.

The coronavirus disease 2019 (COVID-19) pandemic has not only challenged global health systems but also spurred intense scientific inquiry into its pathophysiology. Among the multifaceted aspects of the disease, coagulation abnormalities have emerged as a significant contributor to morbidity and mortality. From endothelial dysfunction to dysregulated immune responses, various factors contribute to the hypercoagulable state seen in severe COVID-19 cases. The dysregulation of coagulation in COVID-19 extends beyond traditional thromboembolic events, encompassing a spectrum of abnormalities ranging from microvascular thrombosis to disseminated intravascular coagulation (DIC). Endothelial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers a cascade of events involving platelet activation, coagulation factor consumption, and fibrinolysis impairment. Moreover, the virus direct effects on immune cells and the cytokine storm further exacerbate the prothrombotic milieu. Unraveling this intricate web of interactions between viral pathogenesis and host responses is essential for elucidating novel therapeutic targets and refining existing management strategies for COVID-19-associated coagulopathy. In the quest to unravel the complex interplay between coagulation and COVID-19, numerous clinical and laboratory studies have yielded invaluable insights into potential biomarkers, prognostic indicators, and therapeutic avenues. Anticoagulation therapy has emerged as a cornerstone in the management of severe COVID-19, although optimal dosing regimens and patient selection criteria remain subjects of ongoing investigation. Additionally, innovative approaches such as targeting specific components of the coagulation cascade or modulating endothelial function hold promise for future therapeutic development.

Demographic Profile and Outcome of Covid- 19 Obstetric Patients Undergoing Caesarean Section in a Tertiary Care Government Hospital in Dhaka, Bangladesh

Background: Pregnancy itself is a hypercoagulable state. COVID-19 infection makes it more deleterious. As a consequence of exaggerated inflammatory response in COVID 19 infected mothers, there is alterations of coagulation system occurs, causing thrombi (micro and macro) in various organs reducing blood flow in capillaries , followed by emboli formation mainly in lung, heart, brain and kidney, resulting in multiple organ failure even death. The present study aims to observe retrospectively the clinical outcome of parturients with COVID-19 infection undergoing caesarean sections. Methods: This observational study was done in the COVID dedicated operation theatre of Department of Anaesthesia, Pain, Palliative and Intensive Care, Dhaka Medical College Hospital, Bangladesh, between May 2020 and December 2021. A total 640 obstetric patients undergoing caesarean section (both COVID positive and suspected) were observed. The demographic and outcome data of mothers ( transferred from post-operative ward to parent ward/ICU) were collected. Informations of ultimate fate (alive/death) of operated mothers were also noted. Demographic (sex) data and outcome data of newborn baby (alive/dead) were also included. The statistical analysis was carried out by using the Statistical Package for Social Sciences version 22.0 for Windows. Results: In this study, the age of the most (n=532, 83.13%) of the pregnant mothers belongs to 18-30 years of age group, remaining 16.86% patients are within the age group of 31-45 years (n=108). Although 18.75% study subjects were illiterate below class VIII(31.25), SSC(17.97%), HSC(16.40%), Graduate(12.5%), masters(3.13%)], miscellaneous type of occupational status [home-maker(70%), service holder(19.85%), entrepreneurship(1.56%) &amp; others(8.59%. and came from different category of social class[ most of the patients belong to lower(54.68%) and lower middle class (27.81%) socioeconomic status]. Among total study sample (n=640), 55.63% (n=356) patients were infected with COVID 19 virus confirmed by RT-PCR and 44.38% (n-284) mothers were clinically COVID infected or suspected cases. The majority of the pregnant mothers (n=565. 88.28%) experienced sub-arachnoid block or spinal anaesthesia whereas only 6.09% (n=39) patients got experience of general anaesthesia. Apparently, 93.44% (n=598) of mothers come back to the parent ward after observing in post-operative ward. Of them, (n=640), 2.19% of mothers were not survived in operation theatre or post-operative ward and 4.34% (n=21)of patients had to go to Covid dedicated Intensive Care Unit. Survivors mothers (n=619, 96.72%) were greater than that of non-survivors (n=21, 3.28%). Among the delivered new born babies, the number of female babies (n=330, 51.56%) were slightly higher than that of male (n=310, 48.44%). In a total 640 babies, 560 babies (87.50%) were survived but 12.50% (n-=80 ) of babies were not survived. Conclusions: This observational study represents that among 640 number of COVID positive or suspected pregnant mothers who were undergoing caesarean section , 93.44% of mothers come back to the parent ward, 2.19% of mothers were expired in operation theatre or post operative ward because of complications. Unfortunanely, 4.34% of mothers had experience to go to Intensive Care Unit. Survivors mothers were greater than that of non-survivors. New born babies of confirmed and suspected COVID mothers were slightly female predominant. Total of them, 87.50% of babies were survived. J Dhaka Med Coll. 2022; 31(2) : 187-193

Mechanisms of Hypercoagulability Driving Stroke Risk in Obesity: A Mendelian Randomization Study.

Obesity is hypothesized to induce a hypercoagulable state that increases stroke risk. The molecular mechanisms underlying this association are largely uncharacterized. We aimed to apply mendelian randomization to identify whether the association of genetically proxied body mass index (BMI) with cardioembolic stroke risk is mediated by changes in levels of circulating coagulation factors. Genetic proxies for BMI and levels of circulating coagulation factors were obtained, respectively, from the Genetic Investigation of ANthropometric Traits consortium (n = 694,649) and deCODE cohort (n = 35,559). Genetic associations with cardioembolic stroke risk were obtained from the GIGASTROKE consortium (10,804 cases and 1,234,804 controls). We performed a two-sample mendelian randomization analysis testing the association of genetically proxied BMI with cardioembolic stroke risk, genetically proxied BMI with levels of coagulation factors, and genetically proxied levels of coagulation factors with cardioembolic stroke risk. These estimates were carried forward to mediation and sensitivity analyses. A 1-SD increase in genetically proxied BMI associated with increased cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD of BMI 1.20, 95% CI 1.08-1.33, p = 8.65 × 10-4) with similar findings in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants. Genetically proxied BMI was further associated with increased levels of Factor VII, Factor Xa, Factor XI, and Protein S (all p < 5.9 × 10-6). Of these factors, genetically proxied levels of Factor XI were associated with cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD increase in Factor XI levels 1.32, 1.19-1.46, p = 6.18 × 10-8). The mediated effect of genetically proxied BMI through Factor XI accounted for 26% (6%-49%) of the total effect of BMI on cardioembolic stroke. Human genetic data support increased levels of Factor XI as a mechanistic explanation for how obesity increases cardioembolic stroke risk. The clinical relevance of this association warrants further investigation within ongoing clinical trials of Factor XI inhibition.

Association of platelet to high-density lipoprotein cholesterol ratio with hyperuricemia

The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia.

Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis

Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

The coagulation status in women of endometriosis with stage IV

BackgroundEndometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV.MethodsThis retrospective case–control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann–Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve.ResultsThe time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717–0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578–0.697), 0.71 (95% confidence interval: 0.656–0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862–0.927) with sensitivity of 88.9% and specificity of 77.7%.ConclusionIn the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

Role of Doppler Ultrasound and Triphasic CT in Differentiation between Benign and Malignant Portal Vein Thrombosis

Abstract Background Portal vein thrombosis is typically a consequence of cirrhosis that already exists, abdominal malignancy, hypercoagulable conditions, or abdominal inflammation. Imaging techniques are used to identify portal vein thrombosis. Once a thrombus has been identified using ultrasound, Doppler ultrasonography can be used to determine if it is benign or malignant. The following step is contrast-enhanced computed tomography or magnetic resonance angiography if more information is needed. If these tests are insufficient, digital subtraction angiography should be carried out. Patients and Methods The study included 40 patients diagnosed by B mode ultrasound to have PVT and referred to the radiology department of the National Hepatology And Tropical Medicine Institute to differentiate between benign and malignant PVT using color Doppler and Triphasic CT. Results those 40 patients were classified according to triphasic CT criteria into 17 patients with benign PVT and 23 patients with malignant PVT which all of them had neovascularity and show early arterial enhancement and delayed wash out. Intra-thrombus pulsatile flow by color Doppler was detected in 19 patients with percentage of agreement 80%, sensitivity of 73.9% and specificity of 88.2%. Conclusion Color Doppler US considered an effective non invasive tool to differentiate between benign and malignant PVT, but it is an operator dependent which need an expertise to detect the vascularity within the thrombus. But is an easy, low cost, available, no contraindications to be done and no exposure to radiation. Although absence of intra-thrombus vasculature doesn`t exclude the malignant nature of the thrombus, and here come the role of Triphasic CT.

IgA Anti-β2-Glycoprotein I Antibodies as Markers of Thrombosis and Severity in COVID-19 Patients.

Patients with COVID-19 may develop a hypercoagulable state due to tissue and endothelial injury, produced by an unbalanced immune response. Therefore, an increased number of thromboembolic events has been reported in these patients. The aim of this study is to investigate the presence of antiphospholipid antibodies (aPL) in COVID-19 patients, their role in the development of thrombosis and their relationship with the severity of the disease. In this retrospective study, serum samples from 159 COVID-19 patients and 80 healthy donors were analysed for the presence of aPL. A total of 29 patients (18.2%) and 14 healthy donors (17.5%) were positive for aPL. Nineteen COVID-19 patients (12%) but no healthy donor presented a positive percentage of the IgA isotype aPL. IgA anti-β2-glycoprotein I antibodies (anti-β2GPI) were the most frequent type (6.3%) in patients but was not detected in any healthy donor. The positivity of this antibody was found to be significantly elevated in patients with thromboembolic events (25% vs. 5%, p = 0.029); in fact, patients with positive IgA anti-β2GPI had an incidence of thrombosis over six times higher than those who had normal antibody concentrations [OR (CI 95%) of 6.67 (1.5-30.2), p = 0.014]. Additionally, patients with moderate-severe disease presented a higher aPL positivity than patients with mild disease according to the Brescia (p = 0.029) and CURB-65 (p = 0.011) severity scales. A multivariate analysis showed that positivity for IgA anti-β2GPI is significantly associated with disease severity measured by CURB-65 [OR (CI 95%) 17.8 (1.7-187), p = 0.0016]. In conclusion, COVID-19 patients have a significantly higher positive percentage of the IgA isotype aPL than healthy donors. IgA anti-β2GPI antibodies were the most frequently detected aPL in COVID-19 patients and were associated with thrombosis and severe COVID-19 and are thus proposed as a possible marker to identify high-risk patients.

P-275 Advanced hemostasis assessment in endometriosis: strengthening confidence in the safety of hormonal treatments

Abstract Study question Are women with endometriosis in a state of systemic imbalance between pro- and anti-coagulants? Summary answer Women with endometriosis do not seem to exhibit a coagulation imbalance, at least at a systemic level. What is known already A state of platelet hyperactivation potentially leading to a hypercoagulation status has been described in women with endometriosis. This phenomenon could induce an altered local environment, promoting platelet-mediated paracrine changes in endometrial tissue and also increasing cardiovascular risk, which could be worsened by the use of estrogen dependent hormonal treatments. However, despite a slight difference in some coagulation parameters has been observed between women affected and controls, their levels remain, generally, within the normal reference range. Study design, size, duration This prospective case-control study including 101 women seeking infertility consultation at the Infertility Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano between January and July 2023 aimed to assess hemostasis function beyond traditional coagulation parameters. Participants/materials, setting, methods Blood of women with endometriosis (n = 51) or tubal or male factor infertility (controls; n = 50) was obtained before any ART treatment, and a complete panel of coagulation tests were performed, including basic parameters (aPTT, PT, FVIII, FII, PC, AT, FIV-C, DD, vWF, ADMT) as well as more sophisticated ones, such as Thrombin Generation Assay and Thromboelastometry, providing data on endogenous thrombin potential (ETP), clot formation time (CFT) and maximal clot firmness (MCF). Main results and the role of chance There were no significant differences between cases and controls in terms of age (37 [34-39] vs 36 [33-39]; p = 0.53, respectively) and smoking habits (14% vs 28%; p = 0.14, respectively). Women affected had a lower BMI compared to controls (22.7 [20.9-24.9] vs 21.4 [19.6-23.8]; p = 0.03), as it is usually expected. Results from TGA were expressed as ETP ratio (with-/without- thrombomodulin), and high ones were indicative of thrombomodulin resistance, taken as indexes of procoagulant imbalance; however, it was not different between women with and without the disease (0.75 [0.65-0.82] vs 0.75 [0.66-0.82]; p = 0.82, respectively). Other markers of procoagulant imbalance evaluated by thromboelastometry were also similar between cases and controls, including CFT (66 sec [58-78] vs 65 sec [59-79]; p = 0.69, respectively) and MCF (65 mm [62-68] vs 66mm [63-68]; p = 0.95, respectively). Considering the vWF/ADAMTS13 ratio, recently proposed to be altered in endometriosis, no difference was seen between affected and no-affected women (0.95 [0.76-1.14] vs 0.91 [0.68-1.15]; p = 0.41, respectively). Finally, all the basic coagulation parameters were also similar between groups. Limitations, reasons for caution Our sample size does not allow us to perform sub-analyses regarding the type of endometriosis, although we cannot exclude differences according to the various manifestations of the disease. Also, not having a systemic haemostasis imbalance does not exclude the possibility of local coagulation imbalances. Wider implications of the findings An altered systemic haemostasis could be worsened by the use of hormonal treatments. Our result indicating that there is no coagulation imbalance at a systemic level reassures about the absence of further contraindications to hormonal drugs as a treatment for endometriosis. Trial registration number not applicable

Clinical characteristics of a COVID-19 cohort treated at UCLA Ronald Reagan Medical Center during the breaking phase of the pandemic: A retrospective study

To this date, COVID-19 remains an unresolved pandemic, and the impairment of redox homeostasis dictates the severity of clinical outcomes. Here we examined initial UCLA cohort of 440 COVID-19 patients hospitalized between March 1st and April 1st, 2020, representing the first wave of the pandemic. The mean age was 58.88 ± 21.12, among which males were significantly more than females (55.5 % vs. 44.5 %), most distinctively in age group of 50–69. The age groups of 50–69 (33.6 %) and ≥70 (34.8 %) dominated. The racial composition was in general agreement with Census data with slight under-representation of Hispanics and Asians, and over-representation of Caucasians. Smoking was a significant factor (28.8 % vs. 11.0 % in LA population), likewise for obesity (BMI ≥30) (37.4 % vs. 27.7 % in LA population). Patients suffering from obesity or BMI<18.5 checked into ICU at a significantly higher rate. A 74.5 % of the patients had comorbidities including diabetes, chronic kidney disease, chronic pulmonary disease, congestive heart failure and peripheral vascular disease. The levels of d-dimer were drastically upregulated (1159.5 ng/mL), indicating hypercoagulative state. Upregulated LDH (328 IU/L) indicated significant tissue damages. A distorted redox hemeostasis is a common trait associated with these risk factors and clinical markers. A quarter of the patients received antivirals, among which Remdesivir most prescribed (23.6 %). Majority received antithrombotics (75 %), and antibiotics. Upon admission, 67 patients were intubated or received CPR; 177 patients eventually received intensive care (40.2 %). While 290 were discharged alive, 10 remained hospitalized, 73 were transferred, and 36 died with 3 palliatively discharged. In summary, our data fully characterized a Californian cohort of COVID-19 at the breaking phase of the pandemic, indicating that population demographics, biophysical characters, comorbidities and molecular pathological parameters have significant impacts on the evolvement of a pandemic. These provide critical insights into effective management of COVID-19, and future break from another pathogen.

Case Report: COVID-19 and Ischemic Stroke in A 16-Year-Old Patient

Introduction: Recent reports show an increasing trend of ischemic stroke at a young age. Diseases associated with ischemic stroke at a young age, namely hereditary hypercoagulable conditions. Case: In this case a 16-year-old boy with clinical complaints of sudden weakness of the right hand and leg, numbness, loss of appetite, nausea and vomiting. Laboratory tests showed results of increased levels of hemoglobin, hematocrit, erythrocyte count, platelet count, leukocyte count and NLR. The neutrophil-to-lymphocyte ratio (NLR), calculated as a simple ratio between the neutrophil and lymphocyte counts measured in peripheral blood. CT scan examination showed acute infarction in the medial left temporal lobe and old infarction in the left frontal lobe (medial gyrus). Thoracic CT Scan examination showed the results of bilateral pneumonia suggestive of viral. The patient encountered COVID-19. The patient experienced cough and shortness of breath and showed abnormal ABG results, namely respiratory alkalosis, decreased oxygen saturation, fever, increased procalcitonin and increased cardiac markers. Discussion: This case report prompts discussions on various aspects of ischemic stroke in young patients, including the role of COVID-19, hypercoagulable states, hematological abnormalities, and diagnostic challenges, with implications for patient management and future research directions. Conclusion: SARS CoV-2 can affect the nervous system through several mechanisms that cause persistent infection, resulting in neurological diseases, including stroke. Young ischemic stroke is usually hypercoagulable and the most common cause is APS. In this patient, polycythemia was occured,that causes blood flow slows and oxygen supply to the brain is reduced. This can cause ischemic stroke.

Pulmonary perfusion in long-term survivors of COVID-19-related severe acute respiratory distress syndrome treated by extracorporeal membrane oxygenation.

COVID-19associates with a hypercoagulant state and an increased risk for venous thromboembolic events (VTEs). Whether severe COVID-19 infection requiringextracorporeal membrane oxygenation(ECMO) support might lead to chronic pulmonary perfusion abnormalities and chronic thromboembolic pulmonary disease/hypertension remains unclear. The purpose of this study was to evaluate chronic pulmonary perfusion abnormalities in long-term survivors of COVID-19-related severe acute respiratory distress syndrome (ARDS) treated by ECMOat our institution. Pulmonary perfusion was examined by ventilation/perfusion(V/Q) single-photon emission computed tomographyor V/Q planar scintigraphy at least 3 months after ECMO explantation, comorbidities and incidence of thromboembolic events were recorded as well. Of 172 COVID-19 patients treated by ECMO for severe COVID-19 pneumonia between March 2020 and November 2021, only 80 were successfully weaned from ECMO. Of those, 37 patients were enrolled into the present analysis (27% female, mean age 52 years). Median duration of ECMO support was 12 days. In 24 (65%) patients VTE was recorded in the acute phase (23 patients developed ECMO cannula-related deep vein thrombosis, 5 of them had also a pulmonary embolism, and one thrombus was associated with a central catheter). The median duration between ECMO explantation and assessment of pulmonary perfusion was 420 days. No segmental or larger mismatched perfusion defects were then detected in any patient. In conclusion, in long-term survivors of COVID-19-related ARDS treated by ECMO, no persistent pulmonary perfusion abnormalities were detected although VTE was common.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus

ObjectiveTo assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. MethodsA cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. ResultsThe mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8–315.9) vs 158.1 (113.4–201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. ConclusionPatients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Rare presentation of recurrent ovarian carcinoma with secondary Budd–Chiari syndrome: a case report

BackgroundBudd–Chiari syndrome (BCS) is a rare condition, usually associated with hematological disorders such as thrombotic diathesis and hypercoagulability. Serum CA-125 level is an established tumor marker of ovarian malignancy; however, cases of primary BCS may also show raised CA-125 levels. BCS in a case of ovarian carcinoma is usually primary in nature due to hypercoagulable state, and raised CA-125 levels with tender hepatomegaly in a treated case of ovarian carcinoma usually imply metastatic recurrence in the liver. However, our case demonstrates an atypical secondary cause of BCS in such a patient caused by extrinsic compression of IVC due to recurrent disease.Case presentationWe report an unusual case of a 69-year-old female who presented with nausea and abdominal pain. She had a 7-year-old history of endometrioid carcinoma of the right ovary for which she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node dissection along with adjuvant chemotherapy. Currently, she had right hypochondrium tenderness, deranged liver function tests (LFT) and raised CA-125 levels, which raised suspicion of hepatic metastasis. However, CECT abdomen revealed peripheral mottled enhancement of liver with multifocal extrahepatic tumor deposits, one of them causing compression of inferior vena cava (IVC) implying a diagnosis of secondary Budd–Chiari syndrome.ConclusionsIn a background of treated ovarian malignancy with raised CA-125 levels and deranged LFT, primary suspicion is of hepatic tumor recurrence. However, in our case, radiological investigation revealed diagnosis of secondary Budd–Chiari syndrome due to perihepatic metastatic recurrence with the absence of frank intrahepatic lesions.