Thrombophilia Research Articles

Hypercoagulable state and risk of venous thromboembolism in Cushing syndrome.

Cushing syndrome (CS) is an endocrine-metabolic disorder characterized by hypercortisolism. Elevated cortisol levels can induce a hypercoagulable state, increasing the risk of venous thromboembolism (VTE). Both pituitary-origin Cushing disease (CD) and adrenal-origin non-adrenocorticotropic hormone (ACTH)-dependent CS are primarily treated with surgery. The dual impact of surgery and the underlying disease further elevates the risk of VTE, potentially leading to pulmonary embolism, which poses a severe threat to patient survival. Additionally, CS patients in a hypercoagulable state have a higher incidence of cardiovascular diseases and VTE, and even mortality compared with the general population. Untreated active CS patients have a 17.8-fold increased risk of VTE compared to the general population. In recent years, the relationship between the hypercoagulable state in CS and VTE has garnered increasing attention from clinicians. A better understanding of the clinical epidemiological characteristics, pathophysiological mechanisms, and clinical prevention and treatment of VTE and pulmonary embolism in CS can provide valuable references for the standardized use of prophylactic anticoagulant therapy in CS patients.

Right Atrial Thrombus Masquerading as Myxoma.

In-situ right atrial (RA) thrombus is a rare occurrence typically associated with heightened inflammatory or hypercoagulable states. Here, we present a case of in-situ RA thrombus mimicking atrial myxoma in a patient with sepsis and bacteraemia. A 41-year-old man presented with septic arthritis and bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA). A transoesophageal echocardiogram revealed a large pediculated mass resembling atrial myxoma, which was not visible on transthoracic echocardiography performed four days earlier. Cardiac magnetic resonance (CMR) imaging strongly suggested a thrombus, leading to the patient undergoing transcatheter aspiration. Subsequent pathology confirmed an organised fibrin thrombus without evidence of infection. The patient's in-situ RA thrombus likely developed in response to a heightened inflammatory state associated with sepsis. Limited data exist on in-situ RA thrombi in the absence of atrial fibrillation, though some reports suggest a correlation between heightened inflammation and a hypercoagulable state. CMR imaging is invaluable for characterising such masses and can aid in distinguishing a thrombus from a myxoma. Differentiating right atrial (RA) thrombus from myxoma: cardiac magnetic resonance imaging is essential for distinguishing RA thrombus from myxoma, preventing unnecessary surgeries.Hypercoagulable and inflammatory states: spontaneous in-situ RA thrombi can occur without deep vein thrombosis (DVT) or atrial fibrillation, especially in hypercoagulable and inflammatory conditions.Transcatheter aspiration: this less invasive alternative to surgery is effective for large, mobile RA thrombi, reducing embolisation risk.

Thermal Influence on the Heart: The Impact of Hot Weather on Cardiovascular Conditions.

Dear Editor, We are cognisant of the fact that cardiovascular diseases (CVDs) have a considerable impact on public healthcare systems. Cardiovascular disorders rank as the primary global reason of fatality, claiming an estimated 17.9 million lives in 2019, which equates to 32% of all global fatalities. The majority of these deaths, around 85 percent, result from heart attacks and strokes. Low- and middle-income countries tolerate the brunt of heart-related fatalities, accounting for over three quarters of all deaths attributed to these conditions. Additionally, out of the 17 million premature deaths caused by noncommunicable diseases in 2019, CVDs were responsible for 38 percent.1 The prevailing cardiovascular risk factors encompass increasing age, hypertension (commonly referred to as a double-edged sword), diabetes mellitus, tobacco use, obesity, dyslipidaemia, and stress.1,2 A sedentary lifestyle together with poor eating habits have also led to an increased rate of CVS-related illnesses.1 Often overlooked as a risk factor, experiencing high temperatures significantly adds to the increased occurrence of cardiovascular diseases. Multiple studies support the connection between extreme temperatures and heightened cardiovascular risks.2-5 Being exposed to higher temperatures can lead to intravascular volume depletion, haemoconcentration, a hypercoagulable state, electrolyte imbalance, and raised sympathetic activity, placing substantial stress on the heart, especially in individuals with pre-existing cardiovascular disease.3 To investigate cardiovascular mortality associations with extremes of temperatures, Barrak Alahmad et al. assembled daily counts of specific cardiovascular causes of death from 567 cities across 5 continents in overlapping periods ranging from 1979 to 2019, and the city-specific daily ambient temperatures were noted. The findings indicated that higher temperature extremes (99th percentile for heat and 1st percentile for cold) were linked to an increased probability of mortality from various cardiovascular conditions, including ischaemic heart disease, stroke, and heart failure.4 In a case-crossover study conducted using the England and Wales MINAP database, involving 24,861 participants (hospital admissions for myocardial infarction) during the warmest months (June to August) from 2003 to 2009, it was found that each 1-degree Celsius increase in temperature beyond the established threshold of 20 °C temporarily increased the risk of heart attack by 1.9 percent.5 The cardiovascular-related illness and fatalities are quite prevalent in Pakistan. Pakistan due to her geographical location, usually encounters summer temperatures ranging from 45 to 55 degrees Celsius across most areas of the country. ---Continue

Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome

BackgroundHypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome.MethodsThirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry.ResultsPatients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68–0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78.ConclusionIncreased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients.

β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in β-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in β-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 μL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies β-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all β-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-β-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.

Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient: A case report and review of literature

BACKGROUND It is well-described that the coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of thrombotic complications. While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients, reports of COVID-19 associated portal vein thrombosis (PVT) have been uncommon. We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient. CASE SUMMARY A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain. One week earlier, the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir. Physical exam revealed mild right and left lower quadrant tenderness, but was otherwise unremarkable. Significant laboratory findings included white blood cell count 12.5 K/μL, total bilirubin 1.6 mg/dL, aminoaspartate transferase 40 U/L, and alanine aminotransferase 61 U/L. Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches. Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct. Hypercoagulable workup including prothrombin gene analysis, factor V Leiden, cardiolipin antibody, and JAK2 mutation were all negative. Anticoagulation with enoxaparin was initiated, and the patient’s pain improved. He was discharged on apixaban. CONCLUSION It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion, as in the case of our patient. Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders. Viral infections such as Epstein-Barr virus, cytomegalovirus, viral hepatitis, and COVID-19 have all been found to increase the risk of splanchnic venous occlusions, including PVT. In our patient, prompt abdominal imaging led to early detection of thrombus, early treatment, and an excellent outcome. This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

A Bibliometric Analysis of Thromboelastography in Veterinary Clinical Use

The evaluation of coagulation with thromboelastography (TEG) has been of high interest for the last two decades in veterinary medicine. The main cause is the ability to detect hypo-, normo- and hypercoagulative states in a single TEG analysis. In clinical veterinary medicine, the importance of coagulation in terms of course and outcome in many diseases had been realized through research over time. TEG studies had gained importance as traditional coagulation tests were inadequate, especially in cases complicated with hypercoagulation. The bibliometric analysis determined topics, researchers and countries of studies in veterinary clinical use of TEG. According to the Web of Science database, a total of 371 documents in this research field were identified between 1998 and 2023. In 2012, with 39 articles, the highest number of studies were published. The most relevant author was Kristensen A.T. with 39 articles. In the list of corresponding authors’ countries, the first country with 189 authors was determined as the USA. Trend topics and their distribution over time have shown that dogs were the most studied animal species in this field. A high number of studies on the topic hypercoagulability and immune-mediated hemolytic anemia were detected, but in the last 3 years new topics like antithrombotics and rational use were involved. The bibliometric analysis carried out showed the changes over time and the currentness of the subject. The results of the present study could be used in planning future studies in the field of veterinary clinical use of TEG.

Characterization of Unique Pathological Features of COVID-Associated Coagulopathy: Studies with AC70 hACE2 Transgenic Mice Highly Permissive to SARS-CoV-2 Infection.

COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.

Stress-Induced Hypercoagulability: Insights from Epidemiological and Mechanistic Studies, and Clinical Integration.

By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, the findings from numerous prospective cohort studies indicate that stress and hemostatic factors of a hypercoagulable state are associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism. Mendelian randomization studies suggest that these associations are partially causal. The review synthesizes extensive research on the link between acute and chronic stress and hypercoagulability, outlining a potential pathway from stress to thrombosis risk. Consistent with the allostatic load concept, acute stress-induced hypercoagulability, initially adaptive, can turn maladaptive under chronic stress or excessive acute stress, leading to arterial or venous thrombotic events. Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress. Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability. Research into the neuroendocrine, cellular, and molecular bases reveals how stress influences platelet activation coagulation and fibrinolysis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, and thrombopoiesis additionally contribute to stress-induced hypercoagulability. Further research is needed to prove a causal link between chronic stress and hypercoagulability. This includes exploring its implications for the prevention and management of thrombotic diseases in stressed individuals, with a focus on developing effective psychosocial and pharmacological interventions.

Perioperative Hyper-coagulation and Thrombosis: Cost Analysis After Congenital Heart Surgery.

Thrombosis, a major adverse event of congenital heart surgery, has been associated with poor outcomes. We hypothesized that in CHD patients undergoing cardiac surgery, increased perioperative use of pro-coagulant products may be associated with postoperative thrombosis in the setting of hyperfibrinogenemia, leading to greater hospital and blood product costs. Single-center retrospective study. Data from Boston Children's Hospital's electronic health record database was used in this study. All patients undergoing congenital heart surgery between 2015 and 2018 with postoperative fibrinogen levels above 400mg/dl were reviewed. Of 334 patients with high plasma fibrinogen levels, 28 (8.4%) developed postoperative thrombosis (median age: one year, 59% male). In our cohort, 25 (7%) demonstrated evidence of baseline hypercoagulability by one or more panel test results. Thrombosis was associated with greater hospital and blood product costs, longer ventilation times, and longer hospital and ICU length of stays. Preoperative hypercoagulable state (odds ratio: 2.58, 95% CI [1.07, 9.99], p = 0.002), postoperative red blood cell transfusion (odds ratio: 1.007, 95% CI [1.000, 1.015], p = 0.04), and single ventricle physiology (univariate odds ratio: 2.94, 95% CI [1.09, 7.89], p = 0.03) were predictors of postoperative thrombosis. Preoperative hypercoagulable state and intraoperative platelet transfusion were predictors of hospital cost. Thrombosis was associated with worse in-hospital outcomes and higher costs. Preoperative hypercoagulable state and postoperative red blood cell transfusion were significant predictors of thrombosis. Risk prediction models that can guide thrombosis prevention are needed to improve outcomes of patients undergoing congenital heart surgery.

Activated platelet-derived exosomal LRG1 promotes multiple myeloma cell growth

The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.

Underlying Mechanisms of Thrombosis Associated with Cancer and Anticancer Therapies.

Cancer-associated thrombosis (CAT) has been identified as the second most prevalent cause of death after cancer itself. Moreover, the risk of thrombotic events in cancer patients increases due to anticancer drugs, such as tyrosine kinase inhibitors (TKIs). Venous thromboembolism (VTE) as well as arterial thromboembolic (ATE) events are present in CAT. Although VTE occurs more frequently, ATE events are very significant and in some cases are more dangerous than VTE. Guidelines for preventing thrombosis refer mainly VTE as well as the contribution of ATE events. Several factors are involved in thrombosis related to cancer, but the whole pathomechanism of thrombosis is not clear and may differ between patients. The activation of the coagulation system and the interaction of cancer cells with other cells including platelets, endothelial cells, monocytes, and neutrophils are promoted by a hypercoagulable state caused by cancer. We present an update on the pathomechanisms of CAT and the effect of anticancer drugs, mainly targeted therapies with a focus on TKIs. Considering the risk of bleeding associated with anticoagulation in each cancer patient, the anticoagulation strategy may involve the use of FXIa inhibitors, direct oral anticoagulants, and low-molecular-weight heparin. Further research would be valuable in developing strategies for reducing CAT.

A Case of Acute Renal Infarct Secondary to Protein S Deficiency

Renal infarction is an underdiagnosed and underreported condition with multiple etiologies. A 45-year-old man presented with acute pain in the right lumbar region, CT scan showed a wedge shaped, non-enhancing, hypodense lesion in the cortex of the upper pole of the right kidney- suggestive of infarct. A pro-thrombotic workup revealed a protein S deficiency and a heterozygous mutation for MTHFR gene. Protein S is a vitamin-K dependent plasma glycoprotein, the deficiency of which is associated with a hypercoagulable state, which in turn led to renal infarction in this patient.

Advancing Thrombosis Research: A Novel Device for Measuring Clot Permeability.

Thromboembolism, a global leading cause of mortality, needs accurate risk assessment for effective prophylaxis and treatment. Current stratification methods fall short in predicting thrombotic events, emphasizing the need for a deeper understanding of clot properties. Fibrin clot permeability, a crucial parameter in hypercoagulable states, impacts clot structure and resistance to lysis. Current clot permeability measurement limitations propel the need for standardized methods. Prior findings underscore the importance of clot permeability in various thrombotic conditions but call for improvements and more precise, repeatable, and standardized methods. Addressing these challenges, our study presents an upgraded, portable, and cost-effective system for measuring blood clot permeability, which utilizes a pressure-based approach that adheres to Darcy's law. By enhancing precision and sensitivity in discerning clot characteristics, this innovation provides a valuable tool for assessing thrombotic risk and associated pathological conditions. In this paper, the authors present a device that is able to automatically perform the permeability measurements on plasma or fibrinogen in vitro-induced clots on specific holders (filters). The proposed device has been tailored to distinguish clot permeability, with high precision and sensitivity, between healthy subjects and high cardiovascular-risk patients. The precise measure of clot permeability represents an excellent indicator of thrombotic risk, thus allowing the clinician, also on the basis of other anamnestic and laboratory data, to attribute a risk score to the subject. The proposed instrument was characterized by performing permeability measurements in plasma and purified fibrinogen clots derived from 17 Behcet patients and 15 sex- and age-matched controls. As expected, our results clearly indicate a significant difference in plasma clot permeability in Behcet patients with respect to controls (0.0533 ± 0.0199 d vs. 0.0976 ± 0.0160 d, p < 0.001). This difference was confirmed in the patient's vs. control fibrin clots (0.0487 ± 0.0170 d vs. 0.1167 ± 0.0487 d, p < 0.001). In conclusion, our study demonstrates the feasibility, efficacy, portability, and cost-effectiveness of a novel device for measuring clot permeability, allowing healthcare providers to better stratify thrombotic risk and tailor interventions, thereby improving patient outcomes and reducing healthcare costs, which could significantly improve the management of thromboembolic diseases.

The Effects of Different Forms of Contraceptives on the Coagulation Profile

Background: The association between combined oral contraceptive pills and increased risk of venous thromboembolism has been extensively researched but little has been reported on its effects on all haematological parameters and coagulation factors. This study aimed to evaluate the effects of different forms of oral contraceptives on the coagulation profile of female subjects in Enugu metropolis. This case-control study was conducted among women attending the Family planning unit of University of Nigera Teaching Hospital, Ituku Ozalla, Enugu State. Methods: The subjects were 36 women undergoing oral contraceptive medication and the control were 36 healthy women not taking this medication. ABO blood grouping and Full blood count (FBC) were carried out while prothrombin time (PT) and activated partial thromboplastin time (APTT) of test subjects were determined using test kits from Technoclone Austria. Most of the test subjects were found to be of the O + blood group. The haematological profile of test subjects showed a statistically significant increase in Red blood cell (RBC), packed cell volume (PCV), neutrophil, eosinophil, mean platelet volume (MPV) and plateletcrit while showing statisticallysignificant reductions in mean cell volume (MCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), lymphocyte, basophil, platelet volume distribution width (PDW) and red cell distribution widths in comparison to the control group. There was a significant decrease in the PT of test subjects (16.06±1.35 secs) in comparison to the control group (19.63±1.28 secs) while the slight increase in their APTT values was not significant. Conclusion: Thrombotic markers such as increased Red cell markers; RBC, haematocrit and platelet indices; MPV, PCT were increased along with decreased PT levels and prolonged APTT values though not significant can link oral contraceptives medication use to a hypercoagulable state in subjects thereby increasing their risk to venous thromboembolism.

Risk factors for thrombotic events among patients taking immune checkpoint inhibitors: A systematic review and meta-analysis.

e14610 Background: Cancer is well known to be a hypercoagulable state, and several studies suggest that targeted therapies, including immune checkpoint inhibitors (ICIs), may also cause thrombotic events. Despite the identification of multiple risk factors associated with ICI administration, no studies have definitively clarified these factors. This study aims to comprehensively investigate the risk factors of thrombotic events upon ICI use. Methods: We conducted a systematic review and meta-analysis. Search terms included immune checkpoint inhibitors (PD-1, PD-L1, and CTLA-4 inhibitors) and thrombotic events (venous, arterial thrombosis, and immune-related adverse events). The primary endpoint was calculating each risk factor's aggregated odds ratio (OR) for any kind of thrombotic event, including venous and arterial thrombosis. The secondary endpoint was to combine the hazard ratio (HR) for each risk factor on thrombosis formation. Results: Out of 8718 studies found, a total of 13 studies with 10608 patients were included. Most patients had non-small cell lung cancer (37.2%) or melanoma (24.8%) and had advanced disease (stage IV being 84.9%). All possible risk factors included in the studies were extracted, and their OR and HR were aggregated. Notably, previous history of thrombus (OR: 3.01; 95% CI: 1.53-5.92), history of COPD (OR: 1.87; 95% CI: 1.00-3.51), smoking history (OR: 1.69; 95% CI: 1.15-2.48), and BMI higher than 30 (OR: 1.68, 1.37-2.07) were associated with a higher risk of thrombotic events. In multivariate analysis, poor performance status of ECOG PS ≥ 2 (HR: 1.55, 95% CI: 1.02-2.36, I2: 35%) and Khorana risk score ≥ 2 (HR: 1.5, 95% CI: 1.23-1.84, I2: 0%) showed higher thrombotic risk. Conclusions: Similar to the known risk factors for thrombosis, previous history of thrombus, smoking history, and obesity are predictors of future thrombus in patients on ICI treatment. Further studies are needed to know if arterial and venous events happen at different rates and/or are associated with different risk factors. [Table: see text]

Hypercoagulable state in patients with varicose vein thrombophlebitis and the diagnostic value of thromboelastography

The study sought to identify the diagnostic significance of thromboelastography in 44 adult patients with acute superficial thrombophlebitis of lower limbs, diagnosed by duplex scanning. The distribution of the thrombotic process was described according to the Verrel-Steckmeier classification, with types II and III defined as «near the junction thrombosis». The research results testify to the fact that the intensification of the hemostasis process in patients with varicose vein thrombophlebitis has a predominantly structural character, due to the increased density of the formed clot. Patients with acute superficial thrombophlebitis exhibit a hypercoagulable status especially when the thrombotic masses are located near the sapheno-femoral/popliteal junction.

The association of COVID-19 with increased pediatric ventriculoatrial shunt failures: a national retrospective cohort.

During the COVID-19 pandemic, the authors' institution managed ventriculoatrial (VA) shunt complications in 2 teenage patients in close proximity to a symptomatic COVID-19 infection. Systemic thrombotic events are an established complication of COVID-19 infection due to a hypercoagulable state. Thrombotic complications, particularly elevated central venous pressure, can cause VA shunt failure. The true effect of COVID-19 on patients with intravascular devices is currently unknown. In this study, the authors aimed to determine if there was an association between COVID-19 infection and VA shunt failure. TriNetX, an aggregated electronic health record platform, was used to analyze data of more than 13 million US pediatric patients. Two matched cohorts of patients < 18 years of age with a VA shunt were defined. Group 1 (n = 311) had a positive laboratory test for COVID-19 from March 1, 2020, to March 31, 2022. Group 2 (n = 311), a control group, had any medical appointment from March 1, 2020, to March 31, 2022, and never had a positive laboratory test for COVID-19. The authors analyzed outcomes 1 year after testing positive for COVID-19 in group 1, and after the medical appointment in group 2. Outcomes included shunt complications, shunt revisions or replacements, and thromboembolic complications. To protect patient privacy, individual results of fewer than 10 patients are not specified in TriNetX. Group 1 had a greater odds of mechanical shunt complication than group 2 (20% vs 4%, OR 5.71, 95% CI 3.07-10.62). Group 1 had a greater odds of shunt reoperation than group 2 (11% vs < 3%, OR > 3.7, 95% CI 1.72-7.62). There were 1-10 patients in group 1 (≤ 3% of group 1) who experienced a thromboembolism due to the shunt, compared with no patients in group 2 who had a thromboembolism due to the shunt. This analysis demonstrates an association of shunt complications, reoperations, and thromboembolic events in patients with VA shunts following COVID-19 infection.

Study on the Analysis of Gender Trends Among the First Authors of Publications on Budd-Chiari Syndrome.

Budd-Chiari syndrome (BCS) is primarily a disease of hepatic vein blockage, which involves a backflow of blood to the liver. Although there have been many causes linked to this disease, most commonly, it occurs due to hypercoagulable states and blood disorders. In recent times, there has been a fast spread of knowledge regarding early diagnosis and various treatment modalities, which has enabled the prevention of mortality in most cases. This has primarily spread through research articles published in various journals. Thus, the article aims tocompare the gender trend ratios to identify the associated discrepancies in terms of male and female author contributions who have been the primary authors for articles pertaining to this disease. Methodology:A PubMed database between the years 2013 and 2022 was used for the bibliometric analysis. The gender of the primary author was analyzed by NamSor, an application programming interface (API). The statistical analysis was conducted using R software, the ARIMA model, and graphs were prepared using Datawrapper. Out of 667 articles extracted, the analysis showed that there were 455 (68.2%) first male authors and 212 (31.8%) first female authors. We also formulated various other results, which depicted a higher female-to-male author ratio including various journals and different countries. Although there has been an increasing trend of male authors as compared to female authors, this study found that male authorship for research on this disease is still higher. This study depicts that there is a necessity to draw attention to the inequitable systems favoring men over women for publications. The predictive analysis conducted also helps to foresee the trend in the next few years and explains the necessity of addressing the disparities among both genders in healthcare systems.

BILATERAL PULMONARY EMBOLISM MIMICKING ACUTE CHEST SYNDROME IN A PATIENT WITH SICKLE CELL DISEASE: ACASE REPORT AND REVIEW OF THE LITERATURE

Abstract This case report discusses a 24-year-old female with sickle cell disease (SCD) who developed bilateral pulmonary embolism (PE), mimicking acute chest syndrome (ACS) following a cholecystectomy. Despite initial treatment for ACS, the patient\\\'s condition deteriorated, leading to a diagnosis of massive bilateral PE via chest CT angiography. The report underscores the importance of considering PE in SCD patients with respiratory symptoms unresponsive to standard ACS treatment. It highlights the hypercoagulable state in SCD, which increases the risk of venous thromboembolism, including PE. The case emphasizes the necessity for heightened clinical suspicion and appropriate diagnostic measures to improve patient outcomes. Unfortunately, the patient succumbed to septic shock despite aggressive management. This report advocates for comprehensive evaluation strategies in similar clinical scenarios to prevent misdiagnosis and improve survival rates.