Risk Factor For Thrombotic Events Research Articles

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]

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

AbstractPolycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.

Expression level of Wilms' tumor 1 gene and its correlation with clinical features in patients with myeloproliferative neoplasms

Objective: To investigate the expression level of WT1 gene in patients with classical Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) and its correlation with clinical features. Methods: A retrospective study included 252 patients with newly diagnosed MPN in Zhongnan Hospital of Wuhan University from January 2015 to March 2023, including 128 males and 124 females, aged［M（Q1，Q3）］62 (53, 69) years. The WT1-positive group (n=93) and the WT1-negative group (n=159) were split based on the level of WT1 gene expression, and the variations in clinical indicators between the two groups were compared. Its levels of expression in each subtype and its relationships to thrombotic events and clinically significant variables were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis. Results: The WT1 gene expression level in the overall bone marrow samples of 252 patients with newly diagnosed MPN was 0.30% (0.10%, 1.10%). The expression level in primary myelofibrosis (PMF) patients was 1.45% (0.41%, 3.24%), which was higher than 0.15% (0.02%, 0.32%), 0.37% (0.16%, 1.09%) in essential thrombocythemia (ET) and polycythemia vera (PV) patients (both P<0.05). Positive correlations were found between WT1 gene expression levels and JAK2V617F gene mutation load, RDW, MPV (r=0.478, 0.346, 0.236, all P<0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (r=-0.339, -0.170, -0.206, -0.388, all P<0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2V617F gene mutation, and higher levels of RDW, LDH, NEUT, and MPV compared to the WT1-negative group. In contrast, the proportion of triple-negative (negative for all three hot mutations of JAK2V617F, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all P<0.05). The thrombotic event rates of WT1-positive group and WT1-negative group were 32.3% (30/93) and 32.1% (51/159), respectively, and the difference was not statistically significant (P=0.883). Logistic regression analysis showed that male (OR=2.41,95%CI:1.02-5.71,P=0.046) and positive JAK2V617F gene mutation (OR=3.96,95%CI:1.50-10.42,P=0.005) were risk factors for thrombotic events in ET patients. Conclusions: WT1 gene expression is elevated in PMF patients and correlated with indicators of disease progression and transformation in MPN patients. It can be utilized as an auxiliary diagnostic indicator for classical MPN staging but is not correlated with the incidence of thrombotic events. Male and positive JAK2V617F gene mutation are risk factors for thrombotic events in ET patients.

High Risk of Thrombosis in a Prospective Cohort of Adults with Primary Immune Thrombocytopenia

Background: Patients with primary Immune thrombocytopenia (ITP) have an increased risk of bleeding but paradoxically also an increased thromboembolic risk. Aim: The aim of this study was to prospectively assess the occurrence and risk factors of symptomatic venous thrombotic events (VTE) and arterial thrombotic events (ATE) in patients with primary immune thrombocytopenia. Methods: This study included 160 adult patients with primary ITP enrolled in the Vienna ITP Biobank, a dual-center cohort study (Medical University of Vienna; Hanusch Hospital) that prospectively collects data of patients diagnosed with primary ITP (EC 1843/2016). Patients with primary ITP and a history of VTE or ATE, as well as those who experienced new or recurrent thrombotic events (TE) during the observation period, were categorized into two groups: with-thrombosis and without-thrombosis. The patient characteristics were compared using a chi-squared or Fisher's exact test for categorical and for numerical data were performed using the Mann-Whitney-U-test. The association between clinical risk factors and thrombosis were performed by univariable analyses using logistic regression model. Results: Of the 160 ITP patients (Table 1), 22 patients (13.8%) had 25 documented ATE or VTE. These events consisted of 11 ATE (44%), including 7 acute myocardial infarctions, 3 cerebral vascular events (stroke or TIA), and 1 peripheral artery thrombosis, and 14 (65%) venous events (1 superficial vein thrombosis, 7 deep vein thromboses, 2 deep vein thromboses with pulmonary embolism and 4 cases of isolated pulmonary embolism). 8 (36.4%) of 22 patients had a history of thrombosis. 17 (77.3%) patients experienced TE during the median observation period of 2.2 (1-3) years. Of them 14 (82.4%) patients had a new TE and 3 (17.6%) recurrent TE. The cumulative 1- and 5-year incidence of TE accounting for competing mortality were 1.9 % and 5.0%. Four (18.2%) patients with thrombosis died during the follow-up period. The cause of death was unclear for three patients, while one patient died from pulmonary embolism. Patients with thrombosis were significantly older (p=0.001) and had more comorbidities than patients without thrombosis (Table 1). There was no difference in the platelet counts between the groups. Antiphospholipid antibodies were present in 14.4% of the patients, and their prevalence was higher in the thrombosis group (p=0.002). In the univariable regression analysis, factors such as older age ≥75 years (OR 1.06; 95%CI 1.03-1.09, p=0.001) diabetes mellitus (OR 4.02; 95%CI 1.20-13.413, p=0.024), presence of antiphospholipid antibodies (OR 6.04; 95%CI 2.01-25.63, p=0.003), particularly lupus anticoagulant positivity (OR 5.39 95%CI 1.8-13.0, p=0.002), and splenectomy (OR 3.07; 95%CI 1.13-12.63, p=0.031) were significantly associated with a higher risk of arterial and venous thrombotic events among ITP patients. Body-Mas-Index, disease duration, tobacco use, hypertension, and use of corticosteroids or thrombopoietin receptor agonist (TPO-RA) were not associated with increased risk of VTE and ATE. Conclusion: We observed a high rate of ATE and VTE in our patients with primary ITP. Additionally, ITP patients commonly present with typical risk factors for thrombotic events, suggesting a strict management of cardiovascular risk factors. Close monitoring and tailored treatment strategies should minimize the risk of bleeding and thrombotic events.

Risk factors for serious adverse events related to vitamin K antagonists in children with congenital or acquired heart disease: a prospective cohort study

ObjectivesTo assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE). Study designAll children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models. ResultsWe included 405 patients. Median follow-up was 18.7 (9.3–49.4) months. The median TTR was 83.1 % (74.4 %–95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1–1.8]) and 2.3 % (CI95 % [0.9–3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %–99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2–8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6–11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5–15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9–32.0], p = 0.005) was the only risk factor for thrombotic events. ConclusionOverall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Cardiovascular and Venous Thromboembolic Events After Hospital Discharge for COVID-19: A Prospective Single Center Study.

Coronavirus disease 2019 (COVID-19) is associated with an increase in venous thrombotic and cardiovascular (CV) events has been reported during hospitalization. No systematic ultrasound follow-up to evaluate sequelae was ever that took place carried out prospectively associated with the evaluation of CV morbidity-mortality at 3months post-discharge. Consecutive patients hospitalized for COVID-19 in the Amiens-Picardie University Hospital between 1st February and 31st August 2020 were included. The primary objective was the thrombosis incidence at 3months after hospital discharge. Thrombosis was defined as either venous thromboembolism (VTE) or a CV event (CVE: myocardial infarction (MI), stroke or peripheral arterial disease). A secondary objective was to determine the risk factors for thrombotic events. We included 498 patients (279 men; 56%) of median age 66 (55-76)years. The primary composite outcome occurred in 27 patients (5.4%); 19 patients (3.8%) presented a CVE (stroke, n = 5; MI, n = 9; and peripheral arterial disease, n = 5). Two patients (0.8%) presented VTE. Six patients (1.2%) died. In multivariate analysis, a previous CVE was associated with thrombosis (OR 3.11; 95% CI 1.17-8.24). COVID-19 was significantly associated with thrombotic events post hospital discharge. Special attention should be given to CVE in the follow-up of patients with a previous thrombotic event.

Role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria

Objective: This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients. Methods: A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined. Results: The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] (P<0.001). All mutations occurred in exon 2. MUC4 mutation (OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups (P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] (P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group (P=0.487) . Conclusion: MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

#3412 THE THROMBOTIC EVENTS IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT STUDY AND MENDELIAN RANDOMIZATION ANALYSIS

Abstract Background and Aims Thrombotic event in ANCA-associated vasculitis (AAV) was prevalent but not clarified in the causal relationship between AAV and thrombotic events. We tried to identify the clinical characteristics and risk factors of thrombotic events in a large sample-size retrospective cohort and investigate the causal relationship by Mendelian randomization (MR) analysis. Method In this retrospective, observational study, all hospitalized AAV patients were included in a single-center tertiary hospital in China from Jan 2013 to April 2022. Clinical data were collected for multivariate regression analysis to determine the risk factors of thrombotic events. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies. The outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) were extracted from the UK biobank. The inverse variance weighted (IVW) method and weighted median (WM) were performed in MR analysis. Results A total of 1203 primary AAV patients were enrolled, with 11.3% developing thrombotic events, with the average age of 49 (ranging from 43.75 to 59.75), and males occupied 56.3%. AAV patients with thrombosis were older (&amp;gt;65 years, 44.9% vs. 29.9%, P&amp;lt;0.001) and with more commodities like chronic kidney disease (CKD, 22.8%)or artery disease(CAD, 11.8%). The thrombotic incidences were more common in eosinophilic granulomatosis with polyangiitis (EGPA, 19.5%), with prolonged hospitalization without significant difference in hospital mortality. Multivariate regression suggested that age over 65 years (OR = 1.574, P = 0.029), EGPA (OR = 3.686, P = 0.029), elevated D-dimer (&amp;gt;2 mg/L, OR = 7.119, P&amp;lt;0.001), and end-stage renal disease (ESRD) status were associated with thrombosis events in patients with AAV. In addition, MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). Conclusion Thrombotic events were not rare in Chinese patients with AAV with independent risk factors such as highly elevated D-dimer and EGPA, which served as a causal risk factor for DVT and PE.

Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome.

Lupus anticoagulant (LA) may be a cause of poor obstetric outcome. To search the association of LA with risk factors for obstetric complications and adverse gestational outcome. This retrospective cohort was consisted of 2 groups of pregnancies with poor obstetric history; 1) LA (+) gestations (Study Group, n= 20) and 2) LA (-) gestations (Control Group, 78). All patients were admitted to a special antenatal care program and were examined in terms of risk factors for thrombotic events, placenta-related obstetric complications, and poor gestational outcomes. Patients were administered low-dose low-molecular-weight heparin (LMWH), low-dose salicylic acid and low-dose corticosteroid (if necessary) within the framework of a prophylaxis protocol in addition to their already existing medications. We have shown that adverse gestational outcome was 1.7-fold more frequent in LA (+) pregnancies with poor obstetric history (p= 0.039, 70% vs. 41%). Higher rates of autoimmune diseases and hereditary thrombophilia were observed among LA (+) patients compared to LA (-) gestations (35% vs. 10.3%, p< 0.012 and 55% vs. 19.2%, p< 0.003, respectively). To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes and demonstrated that the miscarriage rate was significantly decreased to half in current pregnancies compared to the previous gestations (73.6% vs. 35%, p= 0.003). Autoimmune diseases and hereditary thrombophilia are more frequent in LA (+) pregnancies, and these women are prone to obstetric problems. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA (+) pregnant women.

Thrombosis events in Chinese patients with newly diagnosed multiple myeloma.

A high risk of thrombosis is seen in patients with newly diagnosed multiple myeloma (NDMM), particularly those treated with immunomodulatory drugs (IMiDs). Large cohorts addressing the thrombosis issue of NDMM patients in Asia are lacking. We retrospectively analyzed the clinical information of NDMM patients diagnosed in Zhongshan Hospital Fudan University, a national medical center, from January 2013 to June 2021. Death and thrombotic events (TEs) were the endpoints. To investigate risk factors for TEs, the Fine and Gray competing risk regression models were created, in which unrelated deaths were labeled as competing risk events. A total of 931 NDMM patients were recruited in our study. The median follow-up was 23months [interquartile range (IQR): 9-43months]. Forty-two patients (4.51%) developed TEs, including 40 cases (4.30%) of venous thrombosis and 2 cases (0.21%) of arterial thrombosis. The median time from taking first-line treatment to TEs occurrence was 2.03months (IQR: 0.52-5.70months). The cumulative incidence of TEs was higher in patients treated with IMiDs than in those without IMiDs (8.25 vs. 4.32%, p = 0.038). There was no difference in the incidence of TEs between lenalidomide-based and thalidomide-based groups (7.80 vs. 8.84%, p = 0.886). Besides, TEs occurrence did not adversely affectOS (p = 0.150) or PFS (p = 0.210) in MM patients. Chinese NDMM patients have a lower incidence of thrombosis than those in western countries. The risk of thrombosis was particularly increased in patients treated with IMiDs. TEs were not associated with inferior progression-free survival or overall survival.

Large Vessel Occlusion Related Ischemic Stroke From Vitamin B12-Deficiency Related Homocysteine (P8-5.029)

<h3>Objective:</h3> <h3>Introduction:</h3> Vitamin-B12 deficiency-related homocysteinemia is an infrequent cause of stroke. Homocysteinemia is associated with hypercoagulability, increased cholesterol-synthesis, increased oxidative-stress, reduced apolipoprotein-A1 synthesis needed to make protective high-density lipoprotein (HDL), along with cumulative mechanisms that impair endothelial function¹. We present a case of acute ischemic large vessel stroke in a young patient who was incidentally found to have low Vitamin-B12 related homocysteinemia. <h3>Background:</h3> N/A <h3>Design/Methods:</h3> <h3>Case report:</h3> 33-year-old male presented with acute onset motor-aphasia 30 minutes prior to arrival. Exam was significant for complete motor aphasia, facio-bucco-lingual apraxia and a right nasolabial-fold flattening. CT-head was negative for hemorrhage or acute ischemia and CT angiogram revealed an abrupt cut off of the left M1 segment. Patient received thrombolysis with Tenecteplase (TNK) and was emergently taken for mechanical-thrombectomy. On conventional angiogram, the M1 segment showed restored patency after TNK. Work up for secondary causes of stroke including telemetry, transesophageal echocardiogram, hypercoagulability labs, antinuclear antibody (ANA), and syphilis serology were unremarkable. Vitamin-B12 levels were significantly low at &lt; 148 (normal 213–816pg/ml), folate levels were borderline low at 5.0 (5.4–20ng/ml) and homocysteine was significantly elevated at 35 (5.1–15.4mcmol/l). Patient was treated with dual antiplatelet therapy with aspirin 81mg , clopidogrel 75mg and initiated on B12 and folate supplements. Patient was discharged home with near-complete symptom resolution and occasional word-finding difficulty. <h3>Results:</h3> N/A <h3>Conclusions:</h3> <h3>Discussion:</h3> Vitamin-B12 deficiency increases homocysteine levels which is associated with premature atherosclerosis² and is a risk factor for thrombotic events. While vitamin-supplementation can lower homocysteine levels, the benefits as primary-prophylaxis remain uncertain³. It is worthwhile to consider vitamin-supplementation with folic-acid (2.5 mg) and B-complex vitamin (50 mg B6 and 1 mg B12) ¹ supplements in patients with cryptogenic-strokes who have vitamin-B12 deficiency and homocysteinemia as a plausible cause for stroke. Further studies are needed to understand the pathophysiology of these two entities as risk factors for stroke. <b>Disclosure:</b> Dr. Harish has nothing to disclose. Dr. Rau has nothing to disclose. Dr. Diaz Rojas has nothing to disclose.

Effect of antiplatelet therapy on the incidence, prognosis, and rebleeding of intracerebral hemorrhage.

Antiplatelet medications are increasingly being used for primary and secondary prevention of ischemic attacks owing to the increasing prevalence of ischemic stroke occurrences. Currently, many patients receive antiplatelet therapy (APT) to prevent thromboembolic events. However, long-term use of APT might also lead to an increased occurrence of intracerebral hemorrhage (ICH) and affect the prognosis of patients with ICH. Furthermore, some research suggest that restarting APT for patients who have previously experienced ICH may result in rebleeding events. The precise relationship between APT and ICH remains unknown. We searched PubMed for the most recent related literature and summarized the findings from various studies. The search terms included "antiplatelet," "intracerebral hemorrhage," "cerebral microbleeds," "hematoma expansion," "recurrent," and "reinitiate." Clinical studies involving human subjects were ultimately included and interpreted in this review, and animal studies were not discussed. When individuals are administered APT, the risk of thrombotic events should be weighted against the risk of bleeding. In general, for some patients' concomitant with risk factors of thrombotic events, the advantages of antiplatelet medication may outweigh the inherent risk of rebleeding. However, the use of antiplatelet medications for other patients with a higher risk of bleeding should be carefully evaluated and closely monitored. In the future, a quantifiable system for assessing thrombotic risk and bleeding risk will be necessary. After evaluation, the appropriate time to restart APT for ICH patients should be determined to prevent underlying ischemic stroke events. According to the present study results and expert experience, most patients now restart APT at around 1 week following the onset of ICH. Nevertheless, the precise time to restart APT should be chosen on a case-by-case basis as per the patient's risk of embolic events and recurrent bleeding. More compelling evidence-based medicine evidence is needed in the future. This review thoroughly discusses the relationship between APT and the development of ICH, the impact of APT on the course and prognosis of ICH patients, and the factors influencing the decision to restart APT after ICH. However, different studies' conclusions are inconsistent due to the differences in quality control. To support future clinical decisions, more large-scale randomized controlled trials are required.

Bleeding and thrombotic events in post-cardiotomy extracorporeal life support.

Haemorrhagic and thrombotic complications are known obstacles in extracorporeal life support (ECLS), and patients requiring post-cardiotomy (PC)-ECLS are particularly prone. The objective of this study was to characterize the incidence, type and clinical relevance of bleeding and thrombotic events in patients on PC-ECLS. A total of 504 patients receiving PC-ECLS between 2000 and 2021 at a single centre were included in a retrospective analysis. Incidence and type of haemorrhagic and thrombotic complications in patients on PC-ECLS were assessed. Overall survival was compared, and perioperative risk factors for bleeding and thrombotic events were assessed by binary logistic regression. Of the 504 patients requiring PC-ECLS, 196 patients (38.9%) had 235 bleeding events [surgical site: n = 135 (26.8%); cannulation site: n = 68(13.4%); requiring surgical revision: n = 39 (7.7%); cannulation site change: n = 17 (3.4%); fatal cannulation site bleeding: n = 4(0.8%); intracranial haemorrhage: n = 11 (2.1%); gastrointestinal haemorrhage: n = 8 (1.6%); pulmonary haemorrhage: n = 8 (1.6%); and intra-abdominal/retroperitoneal haemorrhage: n = 5 (1%)]. Overall mortality was higher in patients with major bleeding complications than in patients without bleeding complications (P < 0.0001).A total of 74 patients (14.7%) had 84 thrombotic events [ischaemic stroke, n = 39 (7.7%); cannula/circuit thrombosis, n = 26 (5.2%); peripheral embolism, n = 11 (2.2%); device exchange for haemolysis, n = 8 (1.6%)]. Another 246 patients (48.8%) had at least 1 haemocompatibility-related adverse event. Preoperative dual antiplatelet therapy [adjusted odds ratio (OR): 1.83, 95% confidence interval (CI): 1.063-3.137] and ECLS duration (adjusted OR: 1.14, 95% CI: 1.086-1.197) were identified as independent risk factors for haemorrhage. Prior stroke/transient ischaemic attack (adjusted OR: 1.91, 95% CI: 1.08-3.83) and ECLS duration (adjusted OR: 1.09, 95% CI: 1.04-1.15) were identified as risk factors for thrombotic events. Bleeding complications in patients on ECLS are common and significantly impair survival. Nearly half of the patients were affected by any haemocompatibility-related event.

Cannabis use disorder is not a risk factor for thrombotic events or medical complications following total shoulder arthroplasty

BackgroundIn recent years, there has been an increase in utilization of cannabis. Existing studies have found cannabis use disorder (CUD) to be associated with increased incidence of perioperative complications in lower extremity arthroplasty. However, studies examining CUD following total shoulder arthroplasty (TSA) are limited. The aim of this study was to evaluate the effect of comorbid CUD on 2-year revision and 90-day postoperative outcomes in primary TSA for osteoarthritis. MethodsA retrospective cohort analysis was conducted using the PearlDiver database. Current Procedural Terminology, ICD-9, and ICD-10 codes were used to identify patients undergoing TSA for the indication of osteoarthritis and were divided into a CUD and control group. The primary outcomes of interest were 2-year all-cause revision, 90-day hospital readmission, and 90-day emergency department (ED) visit. Surgical perioperative complications included prosthetic joint infection, periprosthetic fracture, aseptic loosening, articular bearing surface wear, broken prosthesis, and prosthetic dislocation. Univariate analysis and multivariable logistic regression were conducted to analyze the data. ResultsA total of 205,792 patients undergoing TSA were identified. The CUD cohort contained 2058 patients, and the control cohort contained 203,734 patients. After controlling for comorbidities, there were statistically significant differences in 2-year revision outcomes. Multivariable results also showed no association with 90-day medical or surgical complications, with the exception of convulsions, 90-day presentation to an eED, and readmission. Discussion and ConclusionOur study showed that patients with CUD have an increased risk of 2-year all-cause revision, readmission, and ED presentation after undergoing TSA. However, CUD was not found to be an independent risk factor for adverse 90-day medical complications, deep vein thrombosis, or length of stay. The results of this research expand the literature on TSA and comorbid substance use. Further, our findings can assist orthopedic surgeons in counseling patients regarding CUD as a risk factor for complications of TSA.

Bilateral Branch Retinal Vein Occlusion after mRNA-SARS-CoV-2 Booster Dose Vaccination

We report a case of a patient with a bilateral branch retinal vein occlusion (BRVO) 24 h after a booster vaccination with the mRNA-1237 vaccine. Fluorescein angiography, performed at three weeks follow-up, showed vascular leakage and blockage, corresponding to hemorrhage areas associated with ischemic areas in the macula and along the arcades involved in the occlusion. The patient was scheduled for urgent injections of intravitreal ranibizumab and laser photocoagulation of the ischemic areas. To the best of our knowledge, this is the first case described of concomitant bilateral RVO after COVID-19 vaccination. The rapid onset of the side effects in a patient with multiple risk factors for thrombotic events suggests that vulnerable microvascular conditions require detailed investigations before administration of a COVID-19 vaccine.

Thrombotic Events Develop in 1 Out of 5 Patients Receiving ECMO Support: An 11-Year Referral Centre Experience.

The use of extracorporeal membrane oxygenation (ECMO) for critically ill patients is growing rapidly given recent developments in technology. However, adverse events are frequently reported that have potentially devastating impacts on patient outcomes. The information on predictors and risk factors for thrombotic events, especially that focusing on the comparison of veno-arterial and veno-venous ECMO configurations, are still inconsistent and sparse; therefore, we aimed to close this gap. We performed a retrospective analysis of all patients on extracorporeal life support admitted to the intensive care units of a tertiary university center in Europe. From 645 patients, 417 who received extracorporeal life support due to cardiogenic shock (290, 70%), respiratory failure (116, 28%) or hypothermia (11, 3%) were included. In total, 22% (92) of the patients experienced thrombotic events with a similar incidence in both ECMO configurations. Anticoagulation consisted of unfractionated heparin (296, 71%) and argatroban (70, 17%). Univariate Cox analyses identified hemoconcentration and increased maximal clot firmness (thromboelastometry) as risk factors for thrombosis. Moreover, the patients experiencing thrombosis had longer ECMO duration and intensive care stays. ECMO is a specialized life-support modality with a high risk of complications. A longer ECMO duration is associated with thrombosis occurrence in patients receiving ECMO support. Following hemorrhage, thromboembolic complications are common adverse events. However, in contrast to major bleeding, no impact on mortality was observed. The question arises if a protocol with less anticoagulation may have a role to play in the future.

ФАКТОРИ РИЗИКУ ТРОМБОЗУ У ОСІБ, ЯКІ ПЕРЕНЕСЛИ НЕГОСПІТАЛЬНУ ПНЕВМОНІЮ НА ТЛІ КОРОНАВІРУСНОЇ ХВОРОБИ (COVID-19)

The aim of the study was to identify the risk factors for thrombotic events in individuals who have experienced community acquired pneumonia associated with COVID-19 and did not have thrombotic events during the acute period of COVID-19. Materials and methods. 45 individuals were examined in postCOVID-19 period (age - 61.0 (54.0; 68.0) years, males - 22 (48,9 %), females - 23 (51,1 %)). All patients were examined twice: at visit 1 — 45,0 (40,0; 60,0) days from the onset of COVID-19, and at visit 2 — 150,0 (117,5; 160,0) days from the onset of COVID-19. Depending on whether the patients received anticoagulant therapy during post-COVID-19 period, the main group was divided into two subgroups: subgroup 1 included 25 (55,6 %) individuals who received anticoagulants during post-COVID-19 period (the course of acute COVID-19 was moderate in 7 (28,0 %) individuals, and severe or critical in 18 (72.0 %) individuals); subgroup 2 included 20 (44,4 %) individuals who did not receive anticoagulants during post-COVID-19 period (the course of acute COVID-19 was moderate in 12 (60,0 %) individuals and severe in 8 (40,0 %) individuals). Clinical methods, pulse oximetry, laboratory and instrumental methods as well as assessment of the probability of thrombosis according to the Wells and Padua scales were used. Results. There was not any thrombotic event occurred in subgroup 1 during post-COVID-19 period. The duration of anticoagulant use in patients from subgroup 1 was 63,0 (60,0; 90,0) days from the onset of COVID-19 symptoms. In subgroup 2, thrombosis was detected in 5 (25,0%) patients during post-COVID-19 period (4 patients had pulmonary embolism and 1 patient had a combination of pulmonary embolism and acute ischemic stroke). Thrombotic events had occurred before visit 1, at 40,0 (33,0; 45,0) days from the onset of COVID-19, which corresponded to 16,0 (15,0; 18,0) days after the end of anticoagulant therapy. Age, gender, body mass index, and comorbidities (hypertension, obesity, diabetes) were not associated with the occurrence of thrombotic events. Risk factors included severe COVID-19 (p=0,04) and the presence of hereditary thrombophilia. Conclusion. The risk of thrombosis in post-acute COVID-19 period is higher in patients after severe course of the acute period of COVID-19, in the absence of anticoagulant therapy during the post-COVID-19 period. On the other hand, the administration of anticoagulants during at least two months from the onset of COVID-19 symptoms, decreased the risk of thrombosis in the post-COVID-19 period not only in patients with severe course but in patients with critical course of the acute period of COVID-19 as well. Key words: COVID-19, post-COVID-19 period, thrombosis, pulmonary embolism, anticoagulants.

Reevaluation of cardiovascular risk factors for thrombotic events in 580 Japanese patients with essential thrombocythemia.

Risk-adapted therapy is recommended to prevent thrombosis in essential thrombocythemia (ET) patients. An advanced age, a history of thrombosis, and the presence of the JAK2V617F mutation are well-defined risk factors for thrombosis in ET; however, the impact of cardiovascular risk (CVR) factors on thrombosis in ET remains elusive. Therefore, we herein investigated the impact of CVR factors on thrombosis in 580 ET patients who met the 2017 World Health Organization Classification diagnostic criteria. A univariate analysis identified hypertriglyceridemia and multiple CVR factors as strong risk factors for thrombosis (hazard ratio [HR] 3.530, 95% confidence interval [CI] 1.630-7.643, P = 0.001 and HR 3.368, 95% CI 1.284-8.833, P = 0.014, respectively) and hyper-LDL cholesterolemia as a potential risk factor (HR 2.191, 95% CI 0.966-4.971, P = 0.061). A multivariate analysis revealed that hypertriglyceridemia was an independent risk factor for thrombosis (HR 3.364, 95% CI 1.541-7.346, P = 0.002). Furthermore, poor thrombosis-free survival was observed in patients with a serum triglyceride level ≥ 1.2mmol/L (HR = 2.592, P = 0.026 vs. < 1.2mmol/L) or two or more CVR factors (P = 0.011 vs. no CVR factors and P = 0.005 vs. one CVR factor). These results revealed the impact of CVR factors on thrombosis in ET. Since CVR factors are manageable, lifestyle interventions, such as the control of serum triglyceride levels, may effectively prevent thrombosis in ET patients.

Neutrophil to Lymphocyte Ratio (NLR) at Diagnosis Is a Predictor of Venous Thrombosis and Poor Outcome in Patients with Prefibrotic Primary Myelofibrosis

Background Thrombosis is a common complication in patients (pts) with myeloproliferative disease: it represents the product of a dysfunctional interaction between erythrocytes, platelets, leukocytes and endothelium. A pro-inflammatory microenvironment appears to be associated with an increased thrombotic risk. Neutrophil-to-lymphocyte ratio (NLR) reflects the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several diseases, including hematological ones. Recently Carobbio et al. [BCJ, 2022] described NLR as a predictor of venous thrombosis in Polycythemia Vera. No score was specifically developed to assess thrombotic risk in myelofibrosis (MF), and even less is known in the setting of prefibrotic primary myelofibrosis (pre-MF). Aims In a multicenter cohort of pre-MF pts, we retrospectively investigated the relationship between NLR values at diagnosis and the risk of: 1) thrombosis 2) disease progression into overt-MF, accelerated (AP) or blast phase (BP); 3) overall survival (OS). Methods We collected clinical, histopathological and hematological data of 176 pts with a diagnosis of pre-MF, revised according to 2016 World Health Organization criteria, followed at 4 Hematological Centers between 2002 and 2022. NLR values were calculated using data obtained from the complete blood count at diagnosis, as the ratio between absolute neutrophilic count (ANC) and absolute lymphocyte (ALP) count. Pts were dichotomized using the best threshold identified by ROC analysis. Thrombotic complications included arterial (ischemic stroke, myocardial infarction, peripheral arterial disease) and venous (deep vein thrombosis, pulmonary embolism, cerebral and splanchnic vein thrombosis) events. Thrombosis-free survival (TFS) and OS were determined from pre-PMF diagnosis to the first thrombotic event and to death or last contact, respectively. TFS/OS were estimated by Kaplan-Meier analysis; the log-rank test was used to compare TFS/OS differences between risk stratified groups. Results Overall, 176 pts were included in this study. Median age was 63.6 (range 25-80) years; 88 (50%) were male. Majority of pts were JAK2V617F mutated (76,1%). Median NLR value at diagnosis was 3 (range 0,64-41,5). By ROC analysis, 6 was identified as the best cut-off value to dichotomize pts based on NLR; 23 pts (13%) presented NLR >6 at diagnosis. A major thrombotic event occurred before or at diagnosis in 53 pts (30,1%): 29 arterial and 25 venous (one patient had both a venous and arterial event). During the follow-up (FU), 30 pts (17%) developed a thrombosis, for a total of 38 thrombotic events (20 venous and 18 arterial events, accounting for an incidence rate of 1,67 and 1,50 per 100 pts-year, respectively). In statistical analysis, factors significantly associated to thrombosis during the FU were previous thrombosis (p=0.05) and JAK2 V617F mutation (p=0.03). Total leucocyte and platelets count, as well as age, sex and IPSET thrombosis score did not correlate with thrombotic events. Pts with ANC > 9 x10^9/L or ALP count < 1,5x10^9/L at diagnosis showed a trend towards a greater incidence of thrombosis in FU (p=0.06 and p=0.07, respectively). Pts with NLR value > 6 at diagnosis had a significantly higher incidence of venous thrombotic events (p=0.03) and a shorter venous TFS (p=0.004, Figure 1) compared to patients with NLR <6. The NLR value was not predictive of arterial thrombotic risk. After a median FU of 6.14 years (range 0,5-27,96) years, 32 pts (18,2%) died; 22 pts (12,5%) had disease progression: of them, 13 (7,4%) experienced overt MF and 9 (5,1%) evolved into an AP or BP. Pts with NLR value > 6 at diagnosis had a significant shorter OS compared to the group with NLR <6 (median OS 4,93 vs 6,22 months respectively, p=0.02). Conclusions This multicenter study investigated for the first time whether the NLR value at diagnosis could be a predictive marker of thrombotic risk and poor outcome in pre-PMF setting. Previous thrombosis and JAK2V617F mutation are confirmed to be risk factors for thrombotic events also in pre-MF setting. Notably, NLR > 6 at diagnosis emerged as a simple marker to identify pts at higher risk of thrombosis and poor outcome in the pre-PMF setting: pts with a NLR value > 6 have a significantly higher venous thrombotic risk and a shorter venous TFS. Furthermore, NLR group > 6 appears to have a shorter OS. These data are promising but require to be confirmed on a larger scale. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal