Thrombophilia Research Articles

Abstract TMP108: Incidence and Characteristics of Acute Ischemic Stroke after Cardiac Arrest

Introduction: Brain injury is the main cause of death and disability post-cardiac arrest, and hypoxic-ischemic brain injury (HIBI) severity is associated with poor outcomes. There is limited information about the co-occurrence of acute ischemic stroke with HIBI post-cardiac arrest and its impact on outcome. Methods: We performed a retrospective analysis of brain MRI reports from patients with cardiac arrest in a multicenter cohort to evaluate the incidence of acute ischemic stroke and HIBI. Patients with MRI in the first 7 days after cardiac arrest were included. Patients with traumatic brain injury, intracranial hemorrhage, recent neurosurgical procedures, or ischemic stroke at admission were excluded. A secondary manual review by a board-certified vascular neurologist was pursued if the MRI report did not specify the absence of ischemic stroke. Univariate and multivariable analysis was performed to explore the characteristics of the ischemic lesions and to evaluate if it was related to poor functional outcomes (i.e., Cerebral Performance Category of 4-5). Results: Among 396 patients who met the inclusion criteria, 91 had cerebral infarction based on MRI (22.9%). The most common pattern of stroke was multifocal small embolic (51.6%), followed by single embolic (25.3%), watershed (12.1%), territorial (7%), and lacunar (5%). The patients with acute ischemic stroke were older (p<0.01). In the logistic regression, older age, non-witnessed cardiac arrest, and non-shockable rhythm were associated with worse prognosis (p<0.05). The presence of acute ischemic stroke was not significantly associated with the cause of arrest, percutaneous coronary intervention (PCI), or the use of targeted temperature management (TTM). Individuals with acute ischemic stroke had lower rates of HIBI (odds ratio [OR] 0,55 [0.34-0.87], p<0.01). In univariate and multivariate analysis, the presence of acute ischemic stroke was not associated with outcome, as opposed to the presence of HIBI (p<0.01). Conclusion: More than one-fifth of the comatose patients after cardiac arrest present acute ischemic stroke on MRI. The most common pattern is multifocal embolic, which may be related to cardiac embolism and hypercoagulable state after the arrest and not from PCI or cardiac arrest rhythm. The detection of acute ischemic stroke is higher among individuals without HIBI and is not associated with worse outcomes.

Post Thrombotic Syndrome Morbidity in Mechanical Thrombectomy Versus Pharmacomechanical Catheter-Directed Thrombolysis of Iliofemoral Deep Venous Thrombosis

ObjectivesIliofemoral deep venous thrombosis (IFDVT) is strongly associated with post thrombotic syndrome (PTS). Interventional treatment options include catheter-directed thrombolysis (CDT) and pharmacomechanical thrombectomy (PMT). More recently, there has been a wide dissemination of large-bore devices for mechanical thrombectomy (MT). Both treatment types have been shown to be effective in clinical practice; however, the rates of PTS after MT are poorly characterized. MethodsWe conducted a retrospective review of patients with acute IFDVT from 2007 – 2022. Patients were divided into two treatment groups: PCDT and MT with large-bore devices. Our primary endpoint was PTS (Villalta score > 4). Secondary outcomes included vessel patency, mortality, and moderate/severe PTS (Villalta score > 9). Predictors of PTS were analyzed using multivariable logistic regression. ResultsThe median age of our cohort (n = 349) was 49 (IQR 35 - 63) years, 54.2% were female. There were 294 (84.2%) patients treated with PCDT. There were no significant baseline characteristic differences between patients treated with PCDT versus MT aside from increased preoperative anticoagulant use in the MT cohort. The overall rate of PTS was 19.1%. There were no differences in rates of PTS, mod-severe PTS, stent patency, mortality between groups, or hospital length of stay (LOS). However, patients treated with MT had higher rates of single operating room (OR) visit during their admission treatment relative to patients that underwent PCDT (33.3% vs. 9.0% , p < 0.01) and decreased intensive care unit LOS (2 (1-3) vs. 0.5 (0-2), p < 0.01). MT treatment was not a risk factor for the development of PTS (aOR 0.73; [95%CI 0.30, 1.74]; p = 0.47) or associated with increased Villalta score (β: -0.34; [95%CI -1.28, 0.60]; p = 0.47). Infrainguinal DVT extension (aOR 2.18; [95%CI 1.16, 4.09]; p = 0.02), prior DVT (aOR 2.67; [95%CI 1.38, 5.13]; p < 0.01), and a hypercoagulable state (aOR 2.32; [95%CI 1.19, 4.50]; p = 0.01) were associated with increased risk of PTS. ConclusionsTreatment with large-bore MT was not a significant predictor for the development of PTS. MT appears safe, durable, and associated with greater rates of single OR visit relative to PCDT, which suggests that rapid thrombus removal may be of value.

Clinical outcomes of malignant portal vein thrombosis in patients with pancreatic cancer: A retrospective analysis.

784 Background: Portal vein thrombosis (PVT) includes portal vein blockage with a blood clot. Recently, there has been an increase in the incidence of PVT with solid malignancy. Portal vein thrombosis (PVT) is a potentially high-risk complication associated with pancreatic cancer. A hypercoagulable state is frequently observed in pancreatic cancer, with the incidence of thromboembolic events reported to range between 17% and 57%. We wanted to analyze the prevalence of PVT in patients with pancreatic cancer and its impact on hospital outcomes. Methods: We performed a retrospective analysis using the National Inpatient Sample Database (NIS) from 2018 to 2020. Patients with the primary diagnosis of pancreatic cancer and age &gt;18 were diagnosed using ICD-10 codes. They were then stratified based on the presence of portal vein thrombosis. The Chi-square test was used to analyze categorical variables, and the T-test was used to analyze continuous variables. The confounders were adjusted using multivariate regression analysis. We observed the outcomes on mortality, length of stay, and total hospital charges. Results: A total of 336894 patients were diagnosed with a primary diagnosis of pancreatic cancer. Of them, 0.04% (n=13475 patients) were diagnosed with metastatic portal vein thrombosis. The mean age of the patients was 64 years (p &lt;0.001). Out of them, 47% of patients were female. In comparison, the remaining 53% were male (p-value: 0.5). Almost 71% f the patients were White, 13% were African American and 0.09% were Hispanics (p-value &lt;0.001). The presence of PVT was found to be associated with increased mortality in pancreatic patients (aOR 1.6, p-value &lt;0.001) as compared to those without PVT. It was also associated with an increase in mean length of stay (LOS)(7.1 vs 6 days, p-value 0.009) and total hospital charges ($86,000 vs $73794, p-value &lt;0.001). It was also observed that the presence of PVT was associated with increased odds of secondary outcomes, including venous thromboembolism (p-value &lt;0.001), stroke (p-value 0.5), and acute kidney injury (p-value &lt;0.001). Conclusions: The presence of portal vein thrombosis (PVT) in pancreatic cancer patients is associated with significantly worse hospital outcomes. These findings emphasize the importance of early detection and aggressive management of PVT in this patient population. Comparison of hospital outcomes between pancreatic cancer patients with and without portal vein thrombosis. Hospital Outcomes Pancreatic cancer patients with PVT Pancreatic cancer patients without PVT Adjusted Odds Ratio (aOR) 95% CI P-value Mortality 9.4% (n=1310) 7.2% (n=23300) 1.3 0.3-1.5 &lt;0.001 LOS (Days) 7.1 6.0 1.6 1.1-2.3 0.009 Venous thromboembolism (VTE) 11% (n=1645) 4.2% (n=13734) 2.9 2.5-3.3 &lt;0.001 Stroke 0.03% (n=5) 0.02 (n=79) 1.8 0.2-14 0.5 Acute Kidney Injury 21% (n=2970) 20% (n=68499) 1.2 1.09-1.3 &lt;0.001

Beyond Khorana score 2: Molecular correlates of venous thromboembolism in pancreatic cancer.

751 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a hypercoagulable state leading to thrombosis. Risk models such as the Khorana score automatically classify PDAC as intermediate-high risk, and recent guidelines recommend consideration of thromboprophylaxis. However, little is known about the molecular correlates of PDAC for venous thromboembolism (VTE). Methods: We examined clinical and genomic data from the prospective multi-institution COMPASS trial (NCT02750657), which enrolled patients with treatment-naïve metastatic PDAC who underwent a fresh tumor biopsy for real-time whole genome and transcriptome sequencing. Laser capture microdissection was performed. Patients underwent restaging scans at 8-week intervals. Detailed chart review was conducted to focus on VTE risk factors, timing of VTE diagnosis, and anticoagulation. We also compared clinical and molecular factors based on timing of VTE diagnosis. Overall survival was defined as time from VTE to death. Results: Of 268 patients enrolled in the COMPASS trial, 166 patients had detailed clinical data available regarding VTE status. 82 patients (49%) developed a VTE, where 16 (20%) had breakthrough clots. Baseline epidemiological variables were similar for those with and without VTE, including no differences between age, sex, BMI, and baseline CA 19-9. No patients were on routine prophylactic anticoagulation. SMAD4 mutations were more frequently seen in the VTE subgroup (57% vs. 40%, p= 0.04), but no differences were seen in other driver genes (KRAS, TP53, CDKN2A), Moffitt subtype, or homologous recombination deficiency status. Patients who developed an early VTE (within 3 months) had a higher baseline CA 19-9 (median 4015 vs. 891, p= 0.02), and none were port-associated. A higher incidence of KRAS wildtype cases (10%) were observed in the early vs. later VTE groups (p= 0.03), but no differences in KRAS allelic status. There were no differences in burden of SNVs, indels, or SVs. Early VTE occurred in 46% of all basal cases, which are typically more aggressive, and only in 37% of classical subtypes. Overall survival was shorter with early VTE (HR 1.74, p= 0.02). Conclusions: A higher incidence of SMAD4 alterations were observed among patients with metastatic PDAC who developed VTE. VTE diagnosed earlier were associated with shorter survival, suggesting that early thromboprophylaxis should be considered at the time of diagnosis. Clinical trial information: NCT02750657 .

Anti-platelet factor 4 antibody-mediated disorders: an updated narrative review.

Anti-platelet factor 4 (PF4) antibody-mediated disorders are a heterogenous group of diseases characterized by the presence of highly pathogenic immunoglobulins G directed against PF4 and/or PF4/heparin complexes. These antibodies are able to activate platelets, neutrophils and monocytes, thus resulting in thrombocytopenia and a hypercoagulable state. Five different forms of anti-PF4 antibody-mediated disorders have been identified: i) classic heparin-induced thrombocytopenia (cHIT) mediated by heparin and certain polyanionic drugs; ii) autoimmune HIT (aHIT) characterized by the presence of anti-PFA/polyanion antibodies that can strongly activate platelets even in the absence of heparin; iii) spontaneous HIT (spHIT) characterized by thrombocytopenia and thrombosis without proximate exposure to heparin, with two subtypes: (a) post-total knee arthroplasty, and cardiac surgery using cardiopulmonary bypass or extracorporeal membrane oxygenation, and (b) post-infections; iv) vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by thrombocytopenia, arterial and venous thrombosis, or secondary hemorrhage after receiving adenoviral vector vaccines for COVID-19; v) VITT-like disorders triggered by adenoviral infections. Though extremely rare and largely unknown, there has been growing interest in the VITT syndrome in recent years due to its clinical relevance. Timely detection of these antibodies is crucial for the diagnosis and treatment of anti-PF4 antibody-mediated disorders, via anti-PF4 antibody immunoassays using several antibody-capture systems (e.g., ELISA based, particle gel, turbidimetry) and functional assays (e.g., serotonin release assay or heparin-induced platelet activation). We aimed to present the latest on laboratory findings, clinical characteristics and therapeutic approaches for anti-PF4 antibody-mediated disorders.

Exploring the relationship between coagulation profiles and histopathological diagnosis of breast lumps: a case control study from Vindhya region, India

Background: Breast cancer is the most common cancer among women in India. The country is on the verge of a potential breast cancer epidemic in the coming decade, driven by lifestyle changes such as delayed marriage and childbirth, influenced by Western trends. Hypercoagulable state is one of the adverse complication seen in cases of breast cancer, according to recent study. Therefore, the purpose of this study was to evaluate the coagulation anomalies in breast cancer patients. Methods: The study was a prospective, case control study carried out with patients presenting with complaints of lump in the breast which were confirmed to be malignant by histopathological examination. Results: Values of PT and aPTT were found to be comparable in patients with breast cancer when compared with controls. D-Dimers were found to be significantly elevated in patients with breast cancer when compared with controls. D-Dimers were also elevated in cases with high histological grade of cancer and lymphovascular invasion. Conclusions: Elevated levels of plasma D-dimer may offer some insight for the diagnosis breast lump.

Virus-Induced Hypercoagulable State: A Mythical Cause for Cerebral Venous Sinus Thrombosis in an Adult Male

Virus-Induced Hypercoagulable State: A Mythical Cause for Cerebral Venous Sinus Thrombosis in an Adult Male

The role of D-dimer changes in predicting delivery time in preterm premature rupture of membranes: a retrospective analysis.

Pregnancy induces a hypercoagulable state, characterized by increased coagulation factors and decreased anticoagulants, alongside ongoing fibrinolysis marked by elevated D-dimer (DD) levels. Reference values for DD in pregnancy often exceed the non-pregnant cutoff due to these changes. Elevated DD levels are common in late pregnancy and may correlate with complications such as gestational diabetes, hypertension, and preterm delivery, particularly in cases of preterm premature rupture of membranes (PPROM). This study investigates the association between DD levels, the duration from PPROM diagnosis to delivery, and neonatal outcomes. This retrospective study was conducted at the Department of Perinatology, Etlik City Hospital, Ankara, Turkey, from October 2022 to May 2023. Eighty patients with PPROM between 24 and 36weeks of gestation were included. Routine blood tests and coagulation parameters, including DD, were monitored every other day for 2weeks. Patients were classified into two subgroups based on whether labor occurred within 7days of PPROM diagnosis. Statistical analyses included the Mann-Whitney U test, Student's t test, Chi-square test, Friedman test, Durbin-Conover test, generalized estimating equations (GEE), and ROC analysis. Gestational age at admission was significantly lower in patients who delivered later than 7days post-PPROM. Significant differences were observed in ultrasonographic measurements, with larger fetal parameters in the early delivery group. Higher DD levels at the third follow-up correlated with shorter durations to delivery (p = 0.021). Longitudinal analysis showed significant fluctuations in DD levels over time, particularly near delivery. The GEE analysis demonstrated a strong inverse relationship between DD levels and time to delivery (p = 0.004), supported by ROC analysis (AUROC = 0.811). Elevated DD levels are associated with shorter durations from PPROM diagnosis to delivery, indicating their potential utility in predicting labor onset. Monitoring DD levels may help in clinical decision-making for managing PPROM, including planning neonatal care and timing of interventions.

Hypercoagulability in Tuberculosis: Pathophysiological Mechanisms, Associated Risks, and Advances in Management—A Narrative Review

Tuberculosis (TB) induces a hypercoagulable state characterized by systemic inflammation, endothelial dysfunction, and alterations in the coagulation and fibrinolytic pathways. This review explores the pathophysiological mechanisms underlying hypercoagulability in TB, including increased pro-inflammatory cytokine release, endothelial damage, platelet activation, and reduced anticoagulant and fibrinolytic activity. These factors contribute to an elevated risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), which complicate TB prognosis and treatment. The potential role of adjunctive anti-inflammatory therapies, such as vitamin D, NSAIDs, corticosteroids, and anti-platelet agents, is highlighted as a strategy to mitigate systemic inflammation and reduce thrombotic risks in patients with TB. The challenges of anticoagulation therapy, particularly in managing the interactions between anti-TB medications and traditional anticoagulants, are discussed, along with the potential of novel oral anticoagulants (NOAs) as alternatives. We also address therapy of hypercoagulability in TB within resource-limited settings which requires low-cost diagnostics, accessible anticoagulation options, adjunctive therapies, and preventive strategies integrated into existing healthcare systems. Effective risk stratification and individualized management strategies are vital for reducing the morbidity and mortality associated with thrombotic complications in TB.

Comparison of thromboelastographic profiles and clinical characteristics in children with severe Mycoplasma pneumoniae pneumonia

BackgroundThis study aimed to compare Thromboelastographic (TEG) profiles and clinical characteristics between severe Mycoplasma pneumoniae (MP) pneumonia patients with normal and abnormal TEG parameters.MethodsThe clinical data of 133 children with severe MP pneumonia were retrospectively analyzed. Patients were divided into normal (n = 76) and abnormal (n = 57) TEG groups. Demographic characteristics, clinical manifestations, laboratory findings, imaging features, bronchoscopy results, treatment, complications, and outcomes were compared between groups.ResultsThe abnormal TEG group (42.9%) had longer fever duration (median: 8.5 vs. 7.0 days, P &amp;lt; 0.001) and hospital stay (median: 11.5 vs. 10.0 days, P = 0.003). They also showed higher levels of C-reactive protein (median: 30.2 vs. 20.1 mg/L, P &amp;lt; 0.001), lactate dehydrogenase (median: 334.5 vs. 276.0 U/L, P = 0.001), and D-dimer (median: 1.2 vs. 0.5 μg/ml, P &amp;lt; 0.001). HRCT revealed more lobar consolidation or multilobar involvement (36.8% vs. 18.4%, P = 0.016), and bronchoscopy showed more mucous plug obstruction (28.1% vs. 10.5%, P = 0.008) in the abnormal TEG group. TEG parameters indicated a hypercoagulable state with shorter R time (P &amp;lt; 0.001), shorter K time (P &amp;lt; 0.001), and higher MA (P = 0.003). The abnormal TEG group had higher incidences of coagulopathy (P &amp;lt; 0.001), cardiac involvement (elevated cardiac enzymes: 36.8% vs. 17.1%, P = 0.009; pericardial effusion: 10.5% vs. 1.3%, P = 0.017), and plastic bronchitis (P = 0.006). They also required longer azithromycin courses (median: 15 vs. 14 days, P = 0.026).ConclusionChildren with severe MP pneumonia and abnormal TEG profiles have more severe clinical manifestations, higher inflammatory markers, more extensive lung involvement, and a higher incidence of complications. TEG may help identify high-risk patients and guide management in severe MP pneumonia.

P0322 Global coagulation assays for the assessment of hypercoagulable states in Inflammatory Bowel Diseases.

Abstract Background Inpatients with Inflammatory Bowel Disease (IBD) are at risk for thromboembolic events, but the risk for flaring outpatients is less understood1. Global Coagulation Assays (GCA) (Thrombin generation assay using Calibrated Automated Thrombogram [CAT] and Rotational Thromboelastometry [ROTEM]) have emerged as aiding tools in the assessment of hypercoagulable states2. Methods Cross sectional, case-control study of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Clinical activity indices (Simple Clinical Colitis Activity Index [SCCAI] for UC and Harvey-Bradshaw Index [HBI] for CD) and biomarkers (c-reactive protein [CRP] and fecal calprotectin [FC]) were registered. Exclusion criteria for IBD patients are listed under table 1. CAT values (endogenous thrombin potential [ETP], lag time [lt], peak, time to peak [ttp]) were compared between the IBD group vs healthy controls (HC) after incubation with PPP-Reagent LOW, MP-reagent and PRP-reagent. ROTEM values (clotting time [CT], clot formation time [CFT], alpha angle, maximum clot firmness [MCF], maximum velocity time [MaxVT] and lysis index at 30 min [LI30]) were assessed using the Non-Activated Thromboelastometry (NATEM) assay and compared with reference values. Heat maps and linear regression were modeled to assess for significant correlation and/or association between continuous variables. Results 55 patients (27 CD, 28 UC) and 75 HC have been included. Baseline characteristics of the IBD population are described in Table 1. No differences were regarded in CAT values between the IBD group vs HC, or IBD ROTEM values vs normal ranges (Figure 1). Significant correlation was found between the following variables (all p values &amp;lt;0.05): CAT-peak with PPPlow and MP-reagent with CRP (ρ=0.38 and ρ=0.32, respectively), CAT-ETP with CRP (ρ=0.28), CAT-peak after incubation with the three agents and SCCAI (ρ=0.5 with PPPlow, ρ=0.5 with MP-reagent and ρ=0.42 with PRP-reagent), CAT-ttpeak and SCCAI (ρ=-0.46), ROTEM-ct and CRP (ROTEM-ct and SCCAI (ρ=–0.38) and ROTEM-MaxVT and SCCAI (ρ=-0.45). Linear regression showed significant association of CAT-peak (after incubation with all three agents) with SCCAI (ß=14.25 for PPP-LOW, ß=22.92 for MP-reagent and ß=13.006 for PRP-reagent, all p values &amp;lt;0.05), ROTEM-MaxVT with SCCAI (ß=-26.1, p=0.01) and ROTEM-ct with SCCAI (ß=-18.02, p=0.02). No other significant associations or correlations were found. Conclusion Correlation of GCA values with CRP and SCCAI suggests enhanced thrombin generation and clot formation in symptomatic outpatients with UC, although overall CAT and ROTEM values are similar in IBD and HC groups. No correlation/association was found between CAT and ROTEM variables with Fcal (globally) or HBI in CD.

HMGB1 secretion by resveratrol in NSCLC: A pathway to ferroptosis-mediated platelet activation suppression.

Cancer-associated venous thromboembolism (CAT) is a frequent and serious complication in cancer patients. Resveratrol, a natural compound with reported anti-tumor effects, is not fully understood in its role regarding CAT in lung cancer. This study aims to explore resveratrol's potential to diminish platelet activation induced by lung adenocarcinoma cells and uncover the underlying mechanisms. Clinical data on coagulation function in non-small cell lung cancer (NSCLC) patients were gathered. A549 human lung cancer cells and Lewis mouse lung cancer cells were employed to assess tumor-induced platelet activation and the impact of resveratrol on this process. Western blotting analyzed protein expression, electron microscopy examined extracellular vesicle (EV) morphology, flow cytometry measured platelet activation, reactive oxygen species (ROS), and exocrine protein expression, while ELISA quantified secretory proteins. Tumor control and platelet function were studied in tumor-bearing mice. We identified that hematological profiles of NSCLC patients frequently manifest a hypercoagulable state relative to healthy controls and lung cancer cells could instigate platelet activation, yet resveratrol could attenuate this phenomenon induced by lung cancer. Resveratrol stimulates lung cancer cells to release HMGB1-enriched EVs, promoting platelet ferroptosis and inhibiting platelet activation through increased ROS, lipid peroxidation, and disrupted cystine transporters. In vivo studies confirm that resveratrol inhibits lung cancer cell growth and suppresses tumor-induced platelet activation in mice. Our studies revealed that resveratrol alleviated lung cancer-induced ferroptosis associated platelet activation. This suggests a potential pharmacological approach for preventing and treating both lung cancer and CAT.

The effect of SARS-CoV-2 Omicron BA. 5.2 infection on perioperative physiological indicators in orthopedic patients

ObjectiveThe aim of this study was to investigate the effect of SARS-CoV-2 Omicron BA. 5.2 (hereafter referred to as Omicron BA. 5.2) infection on perioperative physiological indices and to provide clinical considerations for the precautions needed for patients who tested negative for SARS-CoV-2 infection perioperatively.MethodsPatients who underwent time-limited surgery (surgery that must be performed within a certain time) at the Department of Orthopedics of our hospital from September 1, 2022, to March 31, 2023, were divided into an observation group (those with Omicron BA 5.2 and a negative nucleic acid test after December 7, 2022, n = 100) and a control group (those negative for SARS-CoV-2 infection before December 7, 2022, n = 100). Changes in the following factors were compared within and between the two groups: heart rate, mean arterial pressure, oxygenation index at the time of entry into the operating room, incision of the skin and exit from the operating room and the neutrophil‒lymphocyte ratio (NLR), platelet‒lymphocyte ratio (PLR), systemic immune inflammation index (SII), D-dimer level, and fibrinogen degradation product (FDP) level. Changes in interleukin-6 and calcitonin levels were assessed the day after surgery, and multivariate regression analysis of the meaningful results was conducted.ResultsHeart rate, mean arterial pressure, oxygenation index, NLR, PLR, SII, interleukin-6 and calcitonin were similar between the two groups (P > 0.05). The observation group had higher postoperative D-dimer and FDP levels (P < 0.05). Multivariate regression analysis revealed that Omicron BA 5.2 infection, older age and a history of cerebral infarction were associated with increased D-dimer and FDP levels, and their odds ratios (ORs) and confidence intervals are 3.339 [95% CI, 1.372–8.419], P = 0.008; OR, 1.080 [95% CI, 1.023–1.139]; P = 0.005; OR, 10.644 [95% CI, 1.352–83.320], P = 0.025, respectively.ConclusionOmicron BA. 5.2 Infection affects the perioperative coagulation function of orthopedic patients, thereby inducing a hypercoagulable state characterized by significant elevations in D-dimer and FDP levels and increasing the risk of venous thrombosis. This infection had no obvious effect on other physiological indices. Early surgery is feasible, but thrombotic events need to be considered.

Thromboelastometry-Based Profiling of Haemostatic Alterations in Neonatal Sepsis by Causative Pathogens.

Background: Neonatal sepsis is a serious condition with high mortality, especially in premature and low-birth-weight neonates. This study aims to examine whether the haemostatic profile of neonates with sepsis defers depending on the type of bacteria (Gram-positive or Gram-negative), by using the method of Rotational Thromboelastometry (ROTEM). Methods: This single-centre prospective cohort study was conducted on 128 neonates with sepsis, including 95 cases caused by Gram-negative pathogens and 33 cases caused by Gram-positive bacteria. All participants were hospitalised in the Neonatal Intensive Care Unit (NICU). ROTEM parameters were compared between neonates with Gram-positive and Gram-negative infections. Results: The ROTEM parameters were found to be significantly different between neonates suffering from Gram-positive versus Gram-negative infections, with Gram-positive pathogens associated with an increased clotting potential compared to Gram-negative pathogens. This is reflected in the higher ROTEM values such as A10, α-angle, and MCF in the EXTEM and INTEM assays. Multivariant analysis showed that Gram-positive infections were linked to increased clot thickness at 10 min (coefficient: 8.9, CI: 2.8-15.0, p = 0.004), higher maximum clot stability (coefficient: 10.4, CI: 4.3-16.6, p = 0.001), and a bigger α-angle (coefficient: 8.0, CI: 2.7-13.2, p = 0.003). Similar findings were observed in the INTEM assay parameters. Conclusions: Neonatal sepsis caused by Gram-positive bacteria leads to a hypercoagulable haemostatic state, whereas neonates with sepsis caused by Gram-negative bacteria exhibit a more hypocoagulable profile and a higher incidence of haemorrhagic episodes. These findings provide valuable insights into the haemostatic disorders associated with sepsis, and may aid in developing an individualised approach for the treatment of those disorders, dependent on and adapted for the specific type of causative organism.

Trastuzumab-induced Takotsubo Cardiomyopathy leading to LV Thrombosis and Thromboembolic Stroke: A Case Report

Abstract Background Left ventricular thrombus (LVT) formation is an uncommon phenomenon, typically observed in acute cardiac settings and hypercoagulable states. Takotsubo cardiomyopathy (TC) is a reversible condition originally thought to be linked to immense emotional stress. The occurrence of chemotherapy-related cardiotoxicity presenting with TC and LVT formation is a relatively new concept that remains not fully understood. Case Summary We present the case of a 77-year-old woman with Stage IV breast cancer being treated with trastuzumab and capecitabine therapy, who presented to our hospital with symptoms of right-sided weakness, facial droop and slurred speech. She was admitted for acute left frontal lobe infarction due to an occluded distal left posterior M2 branch of the left middle cerebral artery. As part of thromboembolic stroke work-up, TTE was obtained which showed moderately to severely decreased left ventricular systolic function (LVEF 35%) with wall motion abnormalities suggestive of TC and a 0.9 x 1 cm echogenic structure in the LV consistent with LVT. She was started on therapeutic anticoagulation and was discharged on oral warfarin with INR goal of 2-3. Both capecitabine and trastuzumab were held during her hospitalization. Repeat TTE after two weeks showed an LVEF of 60% with normal LV systolic function and absence of any LVT. Symptoms-wise her right-sided weakness was improving. She was continued on capecitabine and warfarin for now, and continued to follow up outpatient with oncology, cardiology and neurology. Discussion This case highlights TC and LVT as rare but life-threatening complications of trastuzumab-induced cardiotoxicity. We emphasize the importance of early diagnosis to prevent further complications, such as acute thromboembolic stroke, and the necessity of prompt therapeutic interventions to reduce morbidity and mortality. Additionally, we address the multifactorial etiology of TC and the need for frequent TTE monitoring in patients undergoing trastuzumab therapy to diagnose these complications early.

Unexplained Multi-Site Thrombosis: A Step-by-Step Strategy for Factor V Leiden Detection in a Hypercoagulable Patient

Thrombotic manifestations involve the development of blood clots within blood vessels. These conditions can occur unexpectedly in different areas and are often linked to life-threatening situations, presenting challenges for both diagnosis and treatment. We present a case of multi-site thrombosis in a patient with a confirmed hypercoagulable state, resulting from a positive factor V Leiden mutation. The patient’s medical history included hypertension, chronic obstructive pulmonary disease, previous thrombotic events, and changes in anticoagulant therapy. This case highlights the challenges associated with multisystem thrombosis and underscores the necessity of employing various diagnostic techniques, such as echocardiography, computed coronary angiography, and Doppler ultrasonography. In this instance, the patient presented with a history of unprovoked lower limb deep vein thrombosis and multiple arterial thromboses. The patient’s treatment regimen comprised anticoagulants, antiplatelet drugs, and vasodilators. While a reduction in thrombus size was noted, complete revascularization could not be attained. Effective diagnosis and treatment of venous and arterial thrombosis often require multimodal imaging. Selective blood test screening can be beneficial in diagnosing or detecting inherited or acquired abnormalities linked to thrombosis development.

Insights into Cancer-Associated Thrombosis Leading Towards Ischemic Stroke.

Stroke leads to significant disability in most patients, whereas cancer elevates the occurrence of stroke. The incidence of cancer-associated stroke (CAS) is projected to rise as a result of improvements in cancer therapies. Various forms of cancer have been demonstrated to be linked to ischemic stroke. Cancer might influence stroke pathophysiology either directly or through coagulation that creates a hypercoagulative state, in addition to infections. Treatment methods for cancer, including chemotherapy, radiotherapy, and surgery, have all been demonstrated to increase the risk of stroke as well. This review discusses the subtypes, epidemiology, pathophysiology, mechanisms of stroke within cancer patients, biomarkers, and signaling pathways of stroke in cancer while providing vital information on the involved transcription factors, treatment, and management of patients with cancer-associated ischemic stroke. Atherosclerosis, extracellular vesicles (EVs), and signaling biomolecules can also affect CAS. Overall, stroke is a significant and not uncommon complication of cancer, and there is an immediate demand for neurologists and oncologists to create strategies for screening and preventing strokes in cancer patients.

Hypercoagulable states in young adults with ischemic stroke in a Stroke Belt state: a retrospective study.

We theorize that the southeastern United States has a higher stroke mortality rate and higher recurrent ischemic stroke rate than the rest of the United States due to (1) an increased prevalence of hypercoagulable states among young adults in the region, (2) failure to diagnose hypercoagulable states as the cause of ischemic stroke in young adults, and (3) underutilization of anticoagulation for ischemic stroke secondary prevention in young adults with hypercoagulable states. In an attempt to investigate this hypothesis, we conducted a retrospective chart review of 311 inpatients with first-ever ischemic stroke from age 18 to 55 years at an Oklahoma academic medical center from 1 July 2011 to 30 April 2017. Using Chi-squared test, we compared the stroke etiologic diagnosis of the attending neurologist at discharge-when hypercoagulable profile results were rarely available-to the diagnosis of a vascular neurologist postdischarge who had access to all available etiologic test results. The inpatient neurologists identified the stroke etiology as hypercoagulable state in 79 patients (25.57%) and undetermined etiology in 105 (33.98%). With the benefit of final hypercoagulable profile results, the postdischarge vascular neurologist identified the stroke etiology as hypercoagulable state in 167 (54.22%, 95% CI 48.64-59.70%, p-value <2.2e-16) and undetermined etiology in 28 (9.09%, 95% CI 6.36-12.83%, p-value 1.03e-14). There was no significant change in the proportion of ischemic strokes classified under all other stroke etiologies. We conclude that hypercoagulable states are a common and underrecognized cause of ischemic stroke in young adults in the U.S. Stroke Belt.

Acute management of massive pulmonary embolism in pregnancy.

•Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but potentially lethal event.•Physiological changes in the coagulation system during pregnancy and puerperium would lead to a hypercoagulable state.•Diagnosis of PE in pregnancy remains a challenge due to physiological changes in pregnancy. There are no validated scoring systems for assessing pregnant/postpartum women with suspected PE. Massive PE should be suspected in all cases with haemodynamic instability in pregnancy.•The Management of massive pulmonary embolism should be timely and aggressive. Thrombolysis for massive PE during pregnancy and the postpartum period has shown to be associated with high maternal and fetal survival (94% and 88%). But other therapeutic options such as (catheter [or surgical] thrombectomy, ECMO) should be considered in the postpartum period, given the high risk of major bleeding with thrombolysis.•Thrombolysis remains the most-used and reasonably successful modality of treatment in pregnancy but should be avoided in the postpartum period as it can cause life-threatening haemorrhage. During the post-partum period, thrombectomy is the treatment of choice. •To understand the pathophysiology of massive PE.•To appreciate the treatment options in pregnancy and postpartum period and their pros and cons.•To understand the need for further work in this area especially in creating a validated algorithm for diagnosing PE in pregnancy and postpartum period.

A clinical study on the screening efficacy of six thrombotic markers TAT, PIC, TM, t-PAI-C, D-D, and FDP for hypercoagulable state in pregnant women.

To investigate the screening efficacy of six thrombotic markers for hypercoagulable state (HCS) in pregnant women, including thrombin-antithrombin III complex (TAT), plasmin-alpha-2 plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue-type plasminogen activator inhibitor complex(t-PAI-C), D-dimer(D-D), and fibrinogen degradation products (FDP). This was a retrospective study. Eighty-five high-risk pregnant women who underwent antenatal examination at Baoding maternal and Child Health Hospital from December 2022 to September 2023 were included as the observation group, while 85 healthy pregnant women without complications or comorbidities who underwent routine antenatal examinations at our hospital were randomly enrolled as the control group. Analyzed the screening value of these six thrombotic markers in pregnant women at risk of HCS. The levels of TAT, PIC, TM, FDP, and D-D in the observation group were significantly higher than in the control group (P < 0.05, respectively). Pearson correlation analysis showed a weak correlation between maternal age and TAT levels (r = -0.179, P< 0.05) as well as between BMI and FDP and D-D (r = 0.214, 0.232, P< 0.05, respectively). Binary logistic regression analysis revealed that abnormal D-D levels were a risk factor for HCS in pregnant women (OR = 0.117, 95% CI: 0.621-0.639, P< 0.05). The area under the joint curve was 0.757, indicating that the model is of certain predictive value for HCS in pregnant women. TAT, PIC, TM, t-PAI-C, D-D, and FDP can used for the screening of HCS in pregnant women and have a certain predictive value for high-risk pregnant women.