Coagulation Abnormalities Research Articles

Cirrhosis Progression Is Not Associated with Clinically Significant Alterations in Global Hemostasis Assessed by Thromboelastography

(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether liver disease severity leads to progressive alterations in the thromboelastography-based assessment of coagulation. (2) Methods: Consecutive patients with cirrhosis and abnormal standard coagulation tests (at least one of International Normalized Ratio > 2, platelet count < 50 × 103/µL, fibrinogen < 200 mg/dL) were analyzed using native thromboelastography. (3) Results: A total of 106 patients were included, of whom 69 (65.1%) had a normal thromboelastography. While the standard coagulation tests were significantly worse in patients in the Child C group (n = 62, 58.5%) than in patients staged in Child A and B, no significant differences existed between any of the thromboelastography variables. Of the 50 patients (47.1%) with an International Normalized Ratio > 2, only two patients (4%) had features of hypocoagulation, while 26% had features of hypercoagulability on thromboelastography. Patients with a platelet count < 50 × 103/µL had significantly lower platelet function as assessed by thromboelastography, yet only eight patients (20%) met the criteria for platelet transfusion. A thromboelastography-based transfusion protocol might lead to a 94.6% reduction in blood product transfusion indications in a simulation where the included patients would require interventional procedures. (4) Conclusion: Standard coagulation tests showed a poor correlation with thromboelastography. Based on thromboelastography, patients with severe, decompensated liver disease have a preserved hemostasis balance despite abnormal standard coagulation tests. Therefore, standard coagulation tests should not be used to guide the administration of blood products in patients with cirrhosis.

Spinal Anesthesia for Open Appendectomy in a Patient With Cystic Fibrosis and Coagulation Abnormalities: A Case of Tailored Anesthetic Management

Spinal Anesthesia for Open Appendectomy in a Patient With Cystic Fibrosis and Coagulation Abnormalities: A Case of Tailored Anesthetic Management

Role of Thrombosis in Neurodegenerative Diseases: An Intricate Mechanism of Neurovascular Complications.

Thrombosis, the formation of blood clots in arteries or veins, poses a significant health risk by disrupting the blood flow. It can potentially lead to major cardiovascular complications such as acute myocardial infarction or ischemic stroke (arterial thrombosis) and deep vein thrombosis or pulmonary embolism (venous thrombosis). Nevertheless, over the course of several decades, researchers have observed an association between different cardiovascular events and neurodegenerative diseases, which progressively harm and impair parts of the nervous system, particularly the brain. Furthermore, thrombotic complications have been identified in numerous clinical instances of neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Substantial research indicates that endothelial dysfunction, vascular inflammation, coagulation abnormalities, and platelet hyperactivation are commonly observed in these conditions, collectively contributing to an increased risk of thrombosis. Thrombosis can, in turn, contribute to the onset, pathogenesis, and severity of these neurological disorders. Hence, this concise review comprehensively explores the correlation between cardiovascular diseases and neurodegenerative diseases, elucidating the cellular and molecular mechanisms of thrombosis in these neurodegenerative diseases. Additionally, a detailed discussion is provided on the commonly employed antithrombotic medications in the context of these neuronal diseases.

Correlations between coagulation abnormalities and inflammatory markers in trauma-induced coagulopathy

IntroductionIn multiple trauma patients, the occurrence of trauma-induced coagulopathy (TIC) is closely associated with tissue damage and coagulation function abnormalities in the pathophysiological process.MethodsThis study established a multiple trauma and shock model in Sprague-Dawley (SD) rats and comprehensively utilized histological staining and radiographic imaging techniques to observe injuries in the intestine, liver, skeletal muscles, and bones. Monitoring activated partial thromboplastin time (APTT), platelet (PLT) count, respiratory rate, blood pressure, and other physiological indicators revealed time-dependent alterations in coagulation function and physiological indicators. Enzyme-linked immunosorbent assay (ELISA) measurements of inflammatory factors Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and vascular endothelial injury marker (Syndecan-1) were also conducted.ResultsExperimental results demonstrated significant changes in tissue structure after multiple traumas, although widespread necrosis or hemorrhagic lesions were not observed. There were time-dependent alterations in coagulation function and physiological indicators. ELISA measurements showed a strong positive correlation between the significant decrease in PLT count and the increase in TNF-α and IL-6 concentrations.DiscussionThe study provides crucial information for the early diagnosis and treatment of TIC. The findings suggest that structured monitoring of coagulation and inflammatory indicators can help in understanding the pathophysiological changes and aid in the management of TIC in multiple trauma patients.

Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis.

The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors, patients who died during the hypercoagulable period of characteristic coagulation abnormality (CAC), and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

The economic and social burden of congenital thrombotic thrombocytopenic purpura (cTTP) in Italy

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare genetic disorder characterized by an abnormal clotting process leading to serious health complications such as thrombocytopenia and hemolytic anemia. Despite its clinical significance, the estimated broader economic and social impacts in Italy on patients and society remain underexplored. Methods: A detailed questionnaire, developed and validated by a panel of cTTP experts, was distributed to healthcare professionals and patient associations to gather comprehensive data on the economic and social burden of cTTP in Italy. The study was focused on direct and indirect costs associated with the disease management of 15 patients with cTTP, as well as out-of-pocket expenses incurred by patients. Results: The analysis revealed that of the 15 patients diagnosed with cTTP in Italy, 60% were adults aged 40-55 years. Productivity loss and diminished quality of life dominated the economic burden of cTTP, accounting for 81.05% of total costs. Direct medical costs, while substantial, represented a smaller portion of the overall financial impact. Additionally, out-of-pocket expenses, though constituting the smallest fraction, underscored the financial contributions made by patients towards their own care management. Conclusion: The findings underscore the need for a multidisciplinary and holistic approach to cTTP management that extends beyond the clinical treatment. Addressing the economic and social implications of the disease is crucial for improving patient well-being and ensuring the sustainability of healthcare systems. The study advocates for increased awareness, research, and access to care for cTTP patients, highlighting the importance of comprehensive support networks to mitigate the disease’s broader societal impacts, estimated to be around 2 million euro for 15 patients in 10 years.

Dietary Antioxidants and Natural Compounds in Preventing Thrombosis and Cardiovascular Disease

Reactive oxygen species (ROS) contribute to endothelial dysfunction, platelet activation, and coagulation abnormalities, promoting thrombus formation. Given the growing interest in non-pharmacological approaches to modulate oxidative stress, we examine the potential of various dietary interventions and antioxidant supplementation in reducing oxidative damage and preventing thrombotic events. Key dietary patterns, such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets, as well as antioxidant-rich supplements like curcumin, selenium, and polyphenols, demonstrate promising effects in improving oxidative stress markers, lipid profiles, and inflammatory responses. This review highlights recent advances in the field, drawing from in vitro, ex vivo, and clinical studies, and underscores the importance of integrating dietary strategies into preventive and therapeutic approaches for managing thrombosis and cardiovascular health. Further research is needed to better understand long-term effects and personalize these interventions for optimizing patient outcomes.

Development of a predictive model for assessing the risk factors associated with recurrence following surgical treatment of chronic subdural hematoma

BackgroundChronic subdural hematoma (CSDH) is a common disease in neurosurgery. Although many studies have investigated the factors affecting the recurrence of CSDH, no comprehensive prediction model has been established for the risk effect of postoperative recurrence of the disease.ObjectiveThis study aims to collect and analyze the data of CSDH patients treated in our hospital to determine the influence of preoperative, postoperative and treatment factors on the recurrence of CSDH, and to establish a corresponding prediction model to provide neurosurgeons with more accurate basis for identifying high-risk patients and guiding treatment.MethodsA total of 431 patients were collected in this study, including 323 patients who underwent traditional hematoma removal and 108 patients who underwent endoscopic hematoma removal. Relevant preoperative and postoperative data and medical history of patients were collected respectively to study the relevant factors affecting postoperative hematoma recurrence of patients, and to establish a prediction model.ResultsA total of 431 patients were enrolled in this study, 71 of whom had subdural blood recurrence. Possible relevant factors were included in univariate logistic regression, and the results showed that the preoperative GCS score, postoperative residual gas, preoperative CT hematoma thickness, coagulation function, unilateral and bilateral surgery, whether statin was taken after surgery, hematoma site, hematoma density and hematoma volume were all P < 0.2. It is a risk factor for recurrence of chronic subdural hematoma. The obtained data were further included in a multi-factor review. Six factors, including preoperative GCS score, postoperative gas residual, abnormal coagulation function, high-density hematoma, large hematoma volume, and irregular statin use after surgery, were independent risk factors for chronic subdural hematoma recurrence (P < 0.05).ConclusionThis study confirmed that six factors, including preoperative GCS score, postoperative gas residual, abnormal coagulation function, high-density hematoma, large hematoma volume, and irregular statin use, were independent risk factors for recurrence of chronic subdural hematoma. At the same time, long-term use of statins can reduce the recurrence rate of hematoma to a certain extent. In addition, the predictive model in this study could help neurosurgeons accurately identify high-risk CSDH patients.

Prevalence of High Activated Partial Thromboplastin Time (aPTT) among Patients with Liver Cirrhosis Department of Medicine at Saidu Group of Teaching Hospital, Swat

Introduction: Chronic liver disease or liver cirrhosis is a disease condition in which fibrosis and the creasing of the liver are not functioning correctly. The severity of cirrhosis depends upon the extent of liver failure. Advanced stages of liver failure that create an abnormal coagulation profile have increased the tendency towards bleeding and have consequently increased the hospitalization rates and mortality among cirrhotic patients. Activated partial thromboplastin time is a test that measures activity of Factors VII, IX, XI, and XII. An increased aPTT is due to decreased synthesis of measuring clotting factors in the sample indirectly decreases synthesis from the liver. Department of Medicine, Saidu Group of Teaching Hospital Swat Duration of study: From 13 August 2020 to 14 Feb 2021. Total 195 cases of cirrhosis are consecutively selected from OPD and activated partial thromboplastin time (aPTT). Results: The mean age of sample was 45.2 + 7.3 years. 68.2% was male gender while 31.8% is female gender. The mean duration of the disease was 7.1 + 2.5 years. The results showed acute decompensation in 34.9% and 30.8% had hospitalization history due to decompensation. Cardiac drug use history was present in 34.9%. The results further showed that 45.1% patients were diagnosed with prolonged aPTT. Conclusion: Prolongation of aPTT is a frequent problem in our local cirrhotic population. Further studies are needed to develop an association of factors that lead to the prolongation of aPTT, its control, and its effect on morbidity and mortality of patients with cirrhosis. Keywords. Liver cirrhosis, coagulation disorders, activated partial thromboplastin time, acute decompensation

Advancements in Vascular Closure Devices for Effective Hemostasis in Femoral Artery Interventions.

With medical technology development, endovascular intervention has been widely used in clinical practice, and the establishment of surgical access through the femoral artery, where most vascular interventions are performed, is a common method. Postoperative hemostasis at the femoral artery puncture site is a key part of interventional procedures and is particularly important to ensure the safety and effectiveness of hemostasis. Some patients undergoing interventional therapy also use anticoagulant and antiplatelet drugs preoperatively and undergo systemic heparin session intraoperatively, which leads to abnormal coagulation, thus increasing the difficulty of hemostasis at the puncture point postoperatively. Certain patients with specific conditions, such as combined vascular calcification, obesity, diabetes mellitus, and renal impairment, present more challenging cases for postoperative puncture point hemostasis. Femoral artery puncture site hemostasis methods include manual compression, arterial compression devices, and vascular closure devices, which are a kind of equipment that helps interventional doctors stop bleeding quickly at the femoral artery puncture site. From the 1990s to the present, vascular occluders with many different concepts and mechanisms have emerged. Based on different hemostatic principles and materials, the mechanisms and principles of action are varied and include sealant occlusion, collagen patch embolization, polyester suture closure, absorbable polyethanol embolic agents, nickel-titanium alloy clips, polydiethanol sealant embolization, and suture bioabsorbable patches. Many studies have compared the hemostatic effect of vascular closure devices with those of manual compression. In this article, we review the hemostatic effects of the 2 modalities and the advances in the use of vascular closure devices in vascular intervention.

Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.

The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end-stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species-specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation-anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ-source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

8254 The Risk Of Thrombotic Complications In Patients With Post-COVID Syndrome Is High Even With Normal Coagulogram Values

Abstract Disclosure: A. Alieva: None. The high risk of thrombotic complications in patients with diabetes, even more increased in the post-Covid period, requires practicing physicians to be especially vigilant and carefully monitor the state of the hemostatic system and the function of the vascular endothelium. Routine laboratory tests may be insufficient for dynamic monitoring and timely detection of abnormalities. In this article, the author proposes the determination of cell adhesion molecules as a predictor of thrombotic complications in patients with type 2 diabetes mellitus in the post-Covid period. In our current study, VCAM-1 levels were elevated in all patients with type 2 diabetes within 24 months of COVID-19 infection and were not associated with increased von Willebrand factor or D-dimer or other coagulation abnormalities. This means that routine determination of coagulogram, D-dimer and von Willebrand factor may miss the stage of prothrombotic changes in the microvasculature. It is possible that an increase in the level of cell adhesion molecules precedes the appearance of other abnormalities in the hemostasiogram. Therefore, for patients with type 2 diabetes after a coronavirus infection with normal coagulogram values, it seems promising to determine the level of VCAM-1 molecules to prevent the occurrence of thrombotic complications. In addition, monitoring this indicator may be useful in determining the effectiveness of preventive therapy. Presentation: 6/3/2024

Factors influencing urinary retention following freehand transperineal prostate biopsy: Insights from a tertiary care center study

ABSTRACT Objectives: In this study, we evaluated the risk factors for urinary retention after freehand transrectal ultrasound (TRUS) guided transperineal prostate biopsy (TPB). Patients and Methods: Data from 102 cases of freehand TPB at a single institution were retrospectively collected and analyzed. All patients underwent magnetic resonance imaging (MRI)-TRUS cognitive fusion TPB using a transperineal needle guide, with systematic biopsies from 10 prostate sectors and additional MRI-guided targeted biopsies. Exclusions comprised patients with coagulation abnormalities, prior prostate surgeries including biopsy, active urinary tract infection, or a lack of pre-biopsy multiparametric MRI. Results: 14/102 (13.72%) had urinary retention and required urethral catheterization for voiding difficulty or discomfort along with a bladder volume of ≥500 ml. Patients with retention exhibited significantly larger prostate volumes (median 75 cc vs. 40 cc; P < 0.05). Receiver operating curve analysis revealed a prostate volume threshold of 57.5 cc and a core number cutoff of 23 for predicting post-TPB urinary retention, with sensitivities of 78.57% and 85.71%, specificities of 75% and 82.95%, positive predictive values of 33.33% and 44.44%, and negative predictive values of 95.75% and 97.33%, respectively, whereas the number of biopsy cores correlated positively with the development of urinary retention (median 25 vs. 22; P < 0.05). Urinary retention was independent of the patient’s age, comorbidities, presenting prostate-specific antigen levels, prebiopsy severity of lower urinary tract symptoms, and use of alpha-blockers. Conclusion: Patients with larger prostates and higher number of biopsy cores are at a higher risk of postfreehand TPB urinary retention and should receive appropriate counselling. Targeted biopsies alone, rather than a full template, may help mitigate urinary retention in these high-risk groups.

Toxic Effects of Tributyltin, Triphenyltin, and SnCl2 on the Development of Zebrafish (Danio rerio) Embryos

ABSTRACTTin (Sn) is one of the heavy metals to which various functions in biological development are attributed in small quantities, for example, a role in cell structure, enzyme activities, and protein and carbohydrate metabolism in fish. Tributyltin (TBT) and triphenyltin (TPT) are endocrine disrupting chemicals that are widely distributed in the aquatic environment. The aim of this study was to investigate the effects of TBT, TPT, and SnCl2 on the embryonic development of zebrafish. In this study, zebrafish embryos were used to observe the acute toxicity of TBT, TPT, and SnCl2. Fish embryo toxicity analysis was performed for different TBT, TPT, and SnCl2 concentrations (1, 5, 10, 15, and 20 ng/L). Fertilized eggs in 24‐well plates (20 eggs in each concentration) were incubated at 26°C for 4 days, and embryo clotting, embryo heartbeat, and morphological abnormalities were recorded after 96 h. Coagulation increased significantly in a dose‐dependent manner, and TBT was able to induce coagulation in zebrafish embryos. Heartbeat changes significantly decreased (p < 0.05) in a dose‐dependent manner at different TBT doses (p < 0.05). The percentage of mortality was higher in embryos at trace levels of TBT, indicating that the embryos are more sensitive to the toxicity of TBT. TBT is therefore extremely toxic and can have fatal consequences for zebrafish embryos, ultimately leading to the extinction of species and a decline in biodiversity in the aquatic environment. After analyzing the images 96 h after fertilization and converting them to a teratogenic index score, it was found that the index for the two compounds TPT and TBT was 4.6 and 9.6 ng/L, respectively.

Assessments of coagulation profile among good glycemic control and poor glycemic control type 2 diabetic patient attending at Wolkite University specialized hospital, Central Ethiopia: a comparative study

IntroductionDiabetes Mellitus (DM) is a worldwide health issue that is defined by elevated blood glucose levels and impaired metabolism of fat, carbohydrates, and proteins. Atherosthrombotic events are very likely to occur in patients with diabetes mellitus. This results in the development of both microvascular and macrovascular complications.ObjectiveTo compare the coagulation profile parameters between patients with good glycemic control and poor glycemic control and to evaluate the association of coagulation profile and glycemic control in type 2 DM patients.Materials and methodsThis study was conducted in Wolkite university specialized hospital on 90 type 2 Diabetics patients among which 45 were with good glycemic control and 45 were with poor glycemic control. Seven ml blood samples were collected from each study participant and analyzed to assess coagulation profile including Platelet Count, activated Partial Thromboplastin Time (aPTT), and Prothrombin Time (PT). Using SPSS 21.0, an independent sample t-test was used for statistical analysis.ResultsAccording to the current study, when comparing Type 2 Diabetes with poor glycemic control to those with good glycemic control, there was an increase in PT and aPTT concentration (statistically significant, p < 0.05). The platelet counts of the two groups did not differ significantly.ConclusionPeople with Type 2 diabetes have altered coagulation profiles, which have demonstrated that hyperglycemia causes abnormalities in coagulation. Patients with Type 2 diabetes who have poor glycemic control are particularly vulnerable to atherothrombotic and hemorrhagic events. In order to prevent the onset of microvascular and macrovascular illness as soon as possible, physicians may find it helpful to evaluate the coagulation profile of diabetic patients.

Comparative Study of Coagulation Profile and Haematological Parameters in Pregnancy-Induced Hypertension (PIH).

Background Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal morbidity and mortality. PIH, including gestational hypertension, pre-eclampsia, and eclampsia, often leads to significant alterations in coagulation profiles and haematological parameters, posing risks for thromboembolic and haemorrhagic complications. This study aimed to compare the coagulation and haematological parameters between women with PIH and normotensive pregnant women. Methods A cross-sectional observational study was conducted on 110 pregnant women, divided into two groups: 55 with PIH and 55 with normotensives. Coagulation markers such as prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), and platelet count were measured. Bleeding and clotting times were also evaluated. Data were statistically analysed using student's t-test and chi-square tests, with p ≤ 0.05 considered significant. Results Women with PIH exhibited significantly lower platelet counts, PT, aPTT, and INR values compared to the normotensive group (p < 0.0001). Thrombocytopenia and prolonged bleeding time were more common in the PIH group, suggesting an increased risk of both bleeding and clotting complications. Proteinuria was observed in 32 women (58.18%) in the PIH group, reflecting the severity of the disease. Additionally, the PIH group had markedly elevated blood pressure levels. Conclusion PIH is associated with significant coagulation and haematological abnormalities, including thrombocytopenia and a hypercoagulable state, which increase the risk of thromboembolic and hemorrhagic events. Routine monitoring of coagulation profiles and haematological parameters in PIH patients is essential for timely interventions and improving maternal and fetal outcomes.

Potential causal relationships between blood metabolites, inflammatory cytokines, and venous thromboembolism.

Venous thromboembolism (VTE) is the abnormal coagulation of blood in deep veins, which impairs venous return and includes deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of VTE is increasing, leading to severe complications and sequelae. Despite the widespread application of multi-omics analyses in vascular disease research, identifying the specific links between various metabolic products, cytokines, and VTE, as well as their potential mediating roles, requires further validation due to confounding factors. Summary statistics for 1,091 metabolites, 309 metabolite ratios (8,299 individuals), and 41 inflammatory cytokines (8,293 individuals) were obtained from the largest genome-wide association studies (GWAS). Summary statistics for VTE (21,021 cases, 391,160 controls), DVT (6,501 cases, 357,111 controls), and PE (10,046 cases, 401,128 controls) were derived from the FinnGen R10 dataset. We initially examined causal relationships using two-sample MR analysis, followed by Two-step Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR) to identify potential mediating mechanisms. We identified causal associations for 78 blood metabolites with VTE, 79 with DVT, and 81 with PE. Among all 41 inflammatory cytokines included, only platelet-derived growth factor BB (PDGF-BB) levels showed a causal relationship with increased risks of VTE, DVT, and PE. MVMR analysis revealed that the associations between glycocholate levels and VTE, DVT, and PE were mediated by PDGF-BB, accounting for 14.54% (p=2.84E-04), 17.10% (p=3.64E-05), and 10.44% (p=1.39E-02), respectively. Furthermore, the associations between dodecanedioate (C12:1-DC) levels and VTE and DVT were also mediated by PDGF-BB, accounting for 12.79% (p=6.10E-04) and 12.17% (p=2.13E-04), respectively. This study reveals significant associations between specific blood metabolites and the risks of VTE, DVT, and PE, with some associations potentially mediated by PDGF-BB.

Hematological abnormalities in liver cirrhosis.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Rectum necrosis in a patient with severe COVID19 infection after CAR-T therapy: a case report

BackgroundCoronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear.Case presentationA 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved.ConclusionsGastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.

Coagulo-Net: Enhancing the mathematical modeling of blood coagulation using physics-informed neural networks

Blood coagulation, which involves a group of complex biochemical reactions, is a crucial step in hemostasis to stop bleeding at the injury site of a blood vessel. Coagulation abnormalities, such as hypercoagulation and hypocoagulation, could either cause thrombosis or hemorrhage, resulting in severe clinical consequences. Mathematical models of blood coagulation have been widely used to improve the understanding of the pathophysiology of coagulation disorders, guide the design and testing of new anticoagulants or other therapeutic agents, and promote precision medicine. However, estimating the parameters in these coagulation models has been challenging as not all reaction rate constants and new parameters derived from model assumptions are measurable. Although various conventional methods have been employed for parameter estimation for coagulation models, the existing approaches have several shortcomings. Inspired by the physics-informed neural networks, we propose Coagulo-Net, which synergizes the strengths of deep neural networks with the mechanistic understanding of the blood coagulation processes to enhance the mathematical models of the blood coagulation cascade. We assess the performance of the Coagulo-Net using two existing coagulation models with different extents of complexity. Our simulation results illustrate that Coagulo-Net can efficiently infer the unknown model parameters and dynamics of species based on sparse measurement data and data contaminated with noise. In addition, we show that Coagulo-Net can process a mixture of synthetic and experimental data and refine the predictions of existing mathematical models of coagulation. These results demonstrate the promise of Coagulo-Net in enhancing current coagulation models and aiding the creation of novel models for physiological and pathological research. These results showcase the potential of Coagulo-Net to advance computational modeling in the study of blood coagulation, improving both research methodologies and the development of new therapies for treating patients with coagulation disorders.