History Of Venous Thromboembolism Research Articles

Targeting Thrombophilia in Sickle Cell Disease with Isoquercetin: Results of a Fixed Dose, Single Center, Phase II Randomized Clinical Trial

Introduction: Sickle cell disease (SCD) is characterized by elevated markers of hemostatic activation and thrombophilia manifesting as arterial stroke and venous thromboembolism (VTE). Anticoagulation for VTE in SCD is associated with an increased risk for bleeding. In cancer patients at high risk for VTE, the flavonoid Isoquercetin (IQ) lowered D-dimer and soluble P-selectin possibly by inhibiting plasma protein disulfide isomerase. In a murine model of SCD, IQ with Hydroxyurea (HU) reduced platelet accumulation and fibrin deposition following laser-induced injury. Given these results, we tested the hypothesis that IQ would be relatively safe and reduce thrombo-inflammatory biomarkers in steady state SCD patients. Methods: We conducted a phase II randomized, double blind, placebo-controlled study at the NIH Clinical Center. Eligible patients had SCD, were 60 days remote from an acute VOC or blood transfusion and were on a stable dose of HU. Study subjects (n=46) were randomly allocated to receive either Isoquercetin 1000 mg daily (n= 23) or placebo (n= 23) for 28 days and were monitored at the beginning and at completion of study. The primary endpoint of the study was the ELISA measured change in plasma sP-selectin levels after 28 days of placebo or study drug exposure. Analysis was performed on an intention to treat principle. D-dimer levels and Thrombin anti-thrombin (TAT) complex were measured by Immunoturbidimetric assays and ELISA. Statistical analyses was performed using analysis of covariance (ANCOVA) and Wilcoxon rank-sum test. Results: The mean (± SD) age of the study population was 40 years (± 11.57), and 56% were female. The majority had HbSS disease and were receiving HU therapy. A subset (28%) reported a prior history of venous thrombosis (VTE) and four of these were on extended duration oral anticoagulation (Table 1). Baseline characteristics between the two study groups were relatively similar. For the primary endpoint, at the end of study the effect of IQ on the change in plasma sP-selectin levels after adjusting for the baseline was not significant (Figure 1) (IQ mean change= 0.10 ± 6.53 vs. placebo mean change= 0.74 ± 4.54; p= 0.66). Since treatment with HU could confound a treatment effect of IQ in a small sample, we compared the change of sP-selectin among those receiving and not receiving HU but did not find any significant difference (p= 0.67). In a sensitivity analysis we did not find an interaction between HU and IQ treatment (p= 0.48). A similar examination for the potential role of VTE history (n= 5 in IQ and n= 8 in placebo arm) as a confounder did not show a VTE effect on change in sP-selectin (p= 0.68) nor an interaction between VTE history and treatment (p= 0.65). In addition to the primary outcome, we explored the effect of IQ treatment on traditional biomarkers of thrombosis. In contrast to studies in patients with cancer, IQ exposure for 28 days did not have a noticeable effect on change from baseline in either D-dimer levels (IQ mean change= 0.15 mcg/ml ± 0.92 vs. placebo mean change= -0.10 mcg/ml ± 2.11; p= 0.82) or thrombin-antithrombin (TAT) complexes (IQ mean change= 0.09 ng/ml ± 1.60 vs. placebo mean change= -0.05 ng/ml ±1.29; p= 0.57). Conclusion: Short term Isoquercetin exposure in steady state SCD did not appreciably lower plasma sP-selectin but was well tolerated, safe and did not have bleeding side effects. Clinical studies of higher dose IQ with greater exposure duration may yield more measurable effects on antithrombotic activity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Monogenic and Polygenic Contributions to Venous Thromboembolism (VTE) and Splanchnic Thrombosis in Patients (pts) with Pancreatic Cancer (PC)

BACKGROUND Cancer-associated VTE is a significant cause of morbidity and mortality. The Khorana score (KS), which includes cancer type, body mass index, and prechemotherapy laboratory studies, is commonly used to stratify the risk of cancer-associated VTE (1). KS has low discriminative ability in some clinical situations (2) and does not include genomic information. We investigated a cohort of 753 pts with PC for germline and somatic predictors of VTE and splanchnic thrombosis and developed a PC-specific polygenic risk score (PC-PRS) to predict VTE. METHODS We manually abstracted clinical risk factors for VTE in pts of European ancestry with PC, sequenced at Dana-Farber Cancer Institute (DFCI). VTE was defined as 1) thrombosis in deep veins of the lower extremities/upper extremities or 2) pulmonary embolism. Splanchnic thrombosis was separately analyzed and defined as thrombosis of the portal, hepatic, splenic, or superior/inferior mesenteric veins. Incident VTE/splanchnic thrombosis was defined as the first occurrence of thrombosis or thrombosis-related death. KS was calculated using pretreatment laboratory values obtained prior to cancer treatment. A genome-wide association study (GWAS) was conducted for time to VTE across 5.35 million common imputed germline variants. A germline PRS was computed by cross-validation: 1) the cohort was split into 5 subsets; 2) GWAS was conducted within 4/5 subsets and PRS weights calculated using pruning and thresholding; 3) each score was predicted into the held out 1/5 subset; 4) this was repeated five times; 5) significance of the association between held-out PRS and VTE was evaluated by permutation. Associations between both PC-PRS and KS and time to VTE were determined. To assess PRS and GWAS specificity, we conducted an association analysis of 5760 solid tumors sequenced at DFCI and treated with anti-neoplastic therapy for which VTE information was available. Pathogenic somatic variants in tumor suppressor genes included truncating variants, splice-site variants affecting consensus nucleotides, or homozygous deletions. For proto-oncogenes, pathogenic calls included gene amplifications and missense variants with functional impact determined using SIFT(3) and Polyphen-2(4). False discovery rate was applied using Benjamini Hochberg (FDR<10%) RESULTS Of 753 pts with PC, 305 (40.5%) underwent PC surgery and 661 (87.8%) received chemotherapy within 6 months (mo) of diagnosis. During a median follow-up of 4.4 years, 223 (29.6%) incident VTEs and 94 (12.5%) splanchnic thromboses were identified. For 529 pts with available KS, 131 (24.8%) were intermediate-risk while the remaining were high-risk. GWAS across 753 samples identified 1 locus that was genome-wide significant for VTE (p<5x10-8). The lead SNP was rs13327332, with the minor allele associated with a significantly lower risk of VTE (HR=0.13, p=2.8x10-8, fig 1) in the PC cohort. The variant was not associated with VTE in other solid tumors. To investigate genome-wide polygenic effects, a risk score was estimated using all GWAS SNPs and evaluated by cross-validation (PC-PRS). Individuals in the top 20% of PC-PRS were at 5-fold higher risk for developing a VTE in the first 6 mo relative to the lowest 20% of PC-PRS, after accounting for the competing risk of death. Cumulative incidence of VTE in the first 6 mo was similar between pts with intermediate and high KS (fold-change=1). After adjusting for sex, age, chemotherapy within 6 months, history of prior VTE, surgery for pancreatic cancer, metastatic disease at time of VTE, and tumor purity, PC-PRS was significantly associated with time to incident VTE (HR=1.9, p=0.02) while KS was not (HR=1, p=0.96, fig 2). The PC-PRS was specific to PC and was not associated with other solid tumors. Analyzing 445 genes for associations between pathogenic somatic alterations and time-to-VTE, CNV amplifications in CIC were associated with significantly higher risk of VTE (HR=2.5, p=0.0001, FDR<10%). MAP3K1 gene alterations (n=12) were associated with 9.3x higher risk of splanchnic thrombosis (p=0.0001, FDR<10%). CONCLUSION We suggest a role for PC-PRS in VTE risk stratification and identify multiple somatic alterations with high effects on VTE incidence. Implementation of PC-PRS and integration with somatic data may provide a more refined risk estimation of VTE risk in PC than current clinical tools permit. Further validation in independent cohorts is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Validation of the Impede VTE Score for Prediction of Venous Thromboembolism in Chinese Patients with Multiple Myeloma: A Retrospective Cohort Study

Background: The risk of venous thromboembolism (VTE) was 9-fold increase in multiple myeloma (MM) compared to the general population. In addition, the mortality rate of MM patients with VTE is three times higher compared to patients without VTE, which makes it so important to identify those at high risk and commit to preventing VTE events. Recently, the IMPEDE VTE score has emerged as a novel risk prediction tool for VTE in MM and has been incorporated and adopted by the NCCN guidelines. The variation in IMPEDE VTE scores is greatly influenced by Asian ethnicity/race, however, it lacks validation, especially for the Chinese populations. Furthermore, the validation of the IMPEDE VTE score's predictive ability for VTE in Caucasian and Black MM is controversial (Blood (2021) 138 (Supplement 1): 2971; Br J Haematol. 2021 Jun;193(6):1213-1219). Therefore, our objective was to validate the predictive ability of the IMPEDE VTE score for VTE in Chinese patients with MM. Methods: We performed a retrospective chart review of all patients with newly diagnosed MM who started chemotherapy at Beijing Jishuitan Hospital between 2011 and 2021 with a minimum of 6 months follow-up. Patients with coexisting tumors, missing data used to calculate VTE scores were excluded. In addition, The SAVED score, simultaneously adopted by the current NCCN Guidelines in risk-stratification of patients with MM receiving IMiD therapy, were analyzed and compared. The scores for IMPEDE VTE and SAVED were calculated from the date of chemotherapy initiation. Statistical analysis included Chi-square, Fisher's test, Wilcoxon rank sum tests, COX hazard, log-rank and K-M survival analysis. A p-value ≤ 0.05 was considered significant and all analysis was completed in SPSS 23.0 and Graphpad Prism version 8.0. Results: Our cohort included 423 newly diagnosed MM patients, 100% Chinese, 221 of whom were male (52.2%) and 141 (33.3%) patients were older than 65 years. Median age and BMI at diagnosis were 60.8 (IQR: 54.0-68.0) years and 24.5 (IQR: 22.2-26.6) kg/m2, respectively. Kaplan Meier survival analysis showed a 5-year survival rate of 53.72%. In the entire cohort, 62 (17.17%) patients developed VTE and 361 patients did not experience VTE within 6 months of treatment onset. The IMPEDE VTE scores at the start of treatment were ≤3 (low risk), 4-7 (moderate risk) and ≥8 (high risk) in 171 (40.43%), 209 (49.41%) and 43 (10.17%) patients, respectively. The median IMPEDE VTE score was 4 (IQR: 2-5) in all patients and 6 (IQR: 4-9) vs. 4 (IQR: 2-5) in the VTE vs. no VTE cohort, respectively (P < 0.001). Patients with MM in the VTE cohort were more likely to have a history of previous VTE (32.3% vs. 3.9％, P < 0.001), paraplegia (9.7% vs. 2.8%, P = 0.011), and extramedullary plasmacytoma (14.5% vs. 4.7%, P = 0.001) compared with no VTE cohort. Within 6 months of treatment initiation, central venous catheter was more frequently used in the VTE cohort as compared to the no VTE cohort (53.2% vs. 20.8%, P < 0.001). The 6-month cumulative incidence of VTE among all patients was 14.7% (95% CI: 11.3%-18%). In univariate Cox hazard analysis, each 1-point increase in IMPEDE VTE score was associated with the occurrence of VTE within 6 months of treatment initiation (HR: 1.33, 95% CI: 1.23-1.44, P < 0.001). According to the IMPEDE VTE score, the 6-month cumulative incidence of VTE was 3.7% (95% CI: 0.1-7.3) , 14.9% (95% CI: 9.9%-20%) and 24.0% (95% CI: 16.3-31.7) in the low-, intermediate- and high-risk groups (P < 0.001, log-rank), respectively (Fig 1A). The c-statistic of the IMPEDE VTE and SAVED scores for predicting VTE within 6 months of treatment initiation was 0.722 (95% CI: 0.647-0.796) and 0.672(95% CI:0.593-0.752), respectively (Fig 1B). The median follow-up of patients was 27.8 months (IQR: 12.1-49.2). On multivariable Cox hazard analysis, VTE within 6 months of treatment initiation was not a predictor of PFS (HR: 0.854, 95% CI: 0.576-1.267, P = 0.434) and OS (HR: 0.853, 95% CI: 0.527-1.379, P = 0.516) after adjusted for age, prognostic stage, cytogenetics, and ASCT. Conclusions: Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM. Both the IMPEDE VTE (P=0.722) and SAVED (P=0.672) scores could statistically predict VTE outcomes in our patient population, and the IMPEDE VTE score outperformed the SAVED score in risk-stratification of Chinese patients with MM treated with IMiD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Performance of D-Dimers in Patients with Prior History of Venous Thromboembolism Based on Anticoagulation Status

Background: D-dimers frequently stay elevated in patients with prior history of venous thromboembolism (VTE). Moreover, D-dimers seem to have lower diagnostic yield in patients presenting with a suspicion of recurrent VTE and it is not clear how D-dimers perform in patients on anticoagulation. Aim: To evaluate the performance of D-dimers in patients with a history of VTE based on anticoagulation status. Methods: The PREDICTORS study is an international prospective multicenter observational cohort study of outpatients with suspected VTE recurrence. The aim is to improve the performance of diagnostic strategies in patients with a suspicion of recurrent VTE. Pre-test clinical probability was assessed, and D-dimers were performed based on local clinical practices. Negative D-dimers were determined based on the manufacturer's threshold for every commercial assay used in each center. Recurrent VTE events (defined as proximal deep venous thrombosis or segmental or more proximal pulmonary embolism) at enrollment and during the 3-month follow-up were assessed and all suspected recurrent events were independently adjudicated. Results: D-dimer measurements were used in the diagnostic management of 482 patients, of which, 168 patients were on anticoagulation and 314 were not on anticoagulation. At enrollment, the prevalence of recurrent VTE was 29.9% (144/482). Moreover, at the index suspicion, 35.1% (169/482) had negative D-dimers. Amongst patients on anticoagulation, 4/90 (4.4%; 95%CI 1.2%-11.0%) and 21/78 (26.9%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. During follow-up, no recurrent VTE occurred in patients with negative D-dimers. Amongst patients without anticoagulation, 2/79 (2.5%; 95%CI 0.3%-8.9%) and 117/235 (49.8%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. One recurrent VTE occurred during follow-up amongst patients with initial negative D-dimers (1.3%; 95%CI 0.0-7.0%). Conclusion: In patients presenting with a suspected recurrent VTE, the prevalence of VTE was high, including in patients receiving anticoagulant therapy. Prevalence of VTE based on D-dimers positivity was comparable between patients on anticoagulation and patients without anticoagulation. False negative rate of D-dimers appears to be higher in patients with a suspicion of recurrent VTE than in patients with a suspected first thromboembolic event. Further studies are needed to assess if a change in the D-dimers cut-off could improve diagnostic yield.

Inferior Vena Cava Filter Use at a Large Community Hospital: A Cross-Sectional Analysis

Introduction: Inferior vena cava (IVC) filters are considered among patients who have sustained a recent lower extremity deep vein thrombosis (DVT) and/or pulmonary embolism (PE) with a contraindication to anticoagulation. IVC filter use has risen in recent decades despite a lack of data on the effectiveness of IVC filters in reducing venous thromboembolism (VTE)-related mortality. Moreover, IVC filters may be associated with significant morbidity, including filter migration, IVC thrombosis, and fatal bleeding. Prolonged insertion of an IVC filter risks endothelialization which renders later attempts at removal ineffective, and raises the risk of complications. In this study, we aimed to characterize the pattern of IVC filter use at a large community-based hospital. Specifically, we characterized the indications for IVC filter insertion, rates of IVC filter removal, and filter-associated complications. Methods: A retrospective cohort study of adult patients (>18 years) who received an IVC filter between January 1, 2005 - February 28, 2022 at Windsor Regional Hospital (WRH), which is a large community-based hospital with academic affiliations in Southwestern Ontario, Canada. Data were collected using RedCAP software and analyzed using descriptive methods. Results: To date, we have reviewed 89 patient charts from 2019-2022. Patients with IVC filters inserted through WRH were most often male (58.4%) with a median age of 68 years. The most common indications for IVC filters included recent VTE (DVT and/or PE within 3 months) and active bleeding (43.8%), and recent VTE with a need for anticoagulation interruption for surgery (32.6%). Approximately 21% (19 patients) of IVC filters were inserted for indications outside recommended guidelines, including: need for interruption of anticoagulation in patients with a remote history of VTE (31.6%) or prior to surgery (15.8%), recent VTE & active bleed but anticoagulant therapy not discontinued (21.1%), surgical prophylaxis (10.5%), recent VTE & risk of bleeding with no active bleed (10.5%), failure of anticoagulation (5.3%), and massive PE with residual DVT (5.3%). Only 34.8% of patients had successful removal of their IVC filter with an average of 1.2 attempts at filter removal per patient. At least 4 patients (4.5%) have experienced complications relating to their IVC filter, including IVC thrombotic occlusion (50%) and IVC filter migration (50%). Conclusions: Approximately 21% of IVC filters were inserted for indications that fall outside of current guidelines at a large community-based hospital in Ontario, Canada. Moreover, 65% of IVC filters were not removed which is consistent with rates reported in other studies, and significantly raises the risk of IVC filter complications. Given that the majority of patient care occurs in the community setting, further efforts are needed to understand patterns of IVC filter use at other community hospitals. As well, our findings further support the need for development of concrete guidelines on indications for IVC filter use and monitoring practices. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence of VTE in Pregnant Women with Sickle Cell Gene Mutation(s): A Retrospective Database Analysis

Purpose/Objective(s): The leading cause of pregnancy-associated mortality in Western countries is venous thromboembolism (VTE) with an absolute incidence of 0.025 to 0.1 percent in the general pregnant population. Noubiap et al reported that sickle cell disease (SCD) patients had a significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6-7.5, p < 0.001), deep vein thrombosis (DVT) (OR 1.1, 95% CI 1.1-1.2, p < 0.001) and pulmonary embolism (PE) (pooled OR 3.7, 95% CI 3.6-3.8, p < 0.001) as compared to patients without SCD [1]. Although sickle cell trait (SCT) and SCD have an increased risk for VTE, the incidence of VTE during pregnancy has not been documented. Our primary objective was to record a composite incidence of VTE among pregnant patients with SCT/SCD. Material/Methods: A retrospective, cross-sectional analysis including pregnant patients with SCT and SCD was conducted at our tertiary care academic medical center. Data was collected between January 2011 and December 2020. Adult women up to 51 years old with hemoglobin electrophoresis proven SCT and SCD were included. Risk factors for VTE such as the patient's body mass index (BMI), COVID status, family history of VTE, and smoking history were included in the analysis. ANOVA and Chi-square tests were used for analysis and to calculate a composite incidence, odds ratio, confidence interval, and p-value. A p-value of <0.05 was considered statistically significant. Data was analyzed using the SAS system. Results: A total of 139 pregnant SCT/SCD patients were included for analysis, out of which, the majority of the patients were SCT (84/139, 60.4%). The mean age at pregnancy was 26.42 (standard deviation 5.72). The type of VTE included DVT 58.3% (14/24) and PE 41.7% (10/24). At our facility, the incidence rate of VTE in pregnancy for SCT/SCD was 17% as compared to 0.025 to 0.1% in the general population. There was no statistically significant difference in the odds of developing VTE between SCD and SCT (OR= 1.09, 95% CI [.45, 2.63]). Only 2.16% of patients had positive COVID infection, as most of the collected data predated the pandemic. Almost one-third of the patients were smokers (45/139) and only 2.88% (4/139) had a family history of VTE. BMI was divided into BMI <30 (38.13%, 53/139) and BMI >30 (61.87%, 86/139). Obesity (OR= 1.03, 95% CI [.4166, 2.56]) and COVID status (OR=2.45, 95% CI [.21, 28.23]) were not found to be significant in our population of patients. Patients with a family history of DVT had a greater odd of developing VTE (OR=50.70, 95% CI [2.63, 977.88]), although the sample may not provide a precise representation of the population mean. Conclusion: Currently, ASH guidelines recommend a conservative approach to VTE prophylaxis unless research suggests benefits [2]. Our analysis found a 17% incidence of pregnancy-associated VTE in our SCT/SCD patients, which is drastically higher than the general population. With such a significant increased incidence in this patient population, especially with current racial disparities in African American maternal mortality rates, more research should be conducted to evaluate the need for thromboprophylaxis/treatment. Additionally, evaluation for specific SCT/SCD guidelines and recommendations to decrease pregnancy-related VTE and mortality rates should be discussed.

Clinical Characteristics of Cohort of 113 Patients with Cancer-Associated Non Bacterial Thrombotic Endocarditis

Background: Clinical presentation of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) patients including type of malignancy, cardiac valves involved, type of thrombotic complications and hematological indices is limited to cases reports and one small clinical series. Patients and Methods: An electronic search of Mayo Clinic clinical and laboratory records (03/31/2002-06/30/2022) with subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE, diagnosis of active cancer, no infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. Results: Ca-NBTE was diagnosed in 113 patients (mean age 63.3±9.7 years, 67.0% female). Majority of our patients had advanced cancer with 94 out of 107 (87.8%) with either stage IV (n=80) or stage III (n=14). Only 3 patients had stage I cancer. The most common origin of malignancy was lung cancer representing 42 cases (37.2%) and pancreatic cancer (n=19, 16.8%) followed by 15 cases (14.1%) of gynecological malignancies (including 9 ovarian, 4 endometrial, and 2 cervical cancers). Eight Ca-NBTE patients (7.1%) had gastrointestinal cancer equally distributed into upper and lower tract. Hematologic malignancy was diagnosed in 7 patients (6.2%) with 3 patients having myeloid malignancy and 4 lymphoid. Five patients in our cohort had two active cancers at the time of Ca-NBTE diagnosis. The predominant histological type of cancer was adenocarcinoma (n=80, 70.8 %). All pancreatic, over 90% of lung, near 90% of gastrointestinal, and almost half of genitourinary cancers were adenocarcinomas. Vast majority of patients had thrombotic complications at the time of diagnosis with 92 (81.4%) patients with embolic complications to the brain, 10 (8.9%) to the spleen, 9 (8.0%) kidney, 6 (5.3) coronary and 3 (2.7%) to the extremities. The platelet count ranged from 10 to 459 x 109/L with almost 50% of patients having thrombocytopenia (<150,000) at the time of Ca-NBTE diagnosis. There were no patients with creatinine clearance less than 30. Prior history of venous thromboembolism was noted in 61 (54.0%) patients of our cohort. Most often affected valve was mitral (n=68) followed by aortic (n=61). Only one heart valve was affected by Ca-NBTE in 93 patients (48 mitral, 42 aortic, and 3 tricuspid). Eighteen patients had Ca-NBTE affecting 2 valves (16 mitral and aortic, 1 mitral and tricuspid) with one patient having all 4 valves involved. Of 104 anticoagulated patients, 76 received low molecular weight heparin, 16 apixaban, 22 unfractionated heparin, 16 warfarin, and 6 rivaroxaban. Conclusion: Ca-NBTE is more common in female patients with underlying pulmonary and pancreatic cancers and will usually present with acute stroke. Mitral valve is the most common involved, but nearly 20% of patients had multiple valves involved. In our cohort most patients were treated with low molecular weight heparin.

Comparison of Strokes in Adult Hospitalized Patients with Sickle Cell Disease and Patients without Sickle Cell Disease: A Nationwide Analysis

Background: Strokes are a common and serious complication of Sickle Cell Disease (SCD). It is the most common cause of stroke in the pediatric population. The risk of recurrent strokes continues into adulthood in SCD population. In this abstract, we quantify the burden of strokes in the SCD population and compare it against the background of strokes in the non-SCD population. Methods: Adult cases with SCD were identified by the International Classification of Disease 10th Revision Diagnosis codes from the National Inpatient Sample Database for 2016-2019. The cases were distributed into age groups based on decades (18-30, 31-40, 41-50, 51-60, 61-70, 71-80; and 81 and above). Cases were identified for the presence of a history of a prior stroke [PMHS] with residual deficits, PMHS without deficits, a new episode of a hemorrhagic stroke, and a new episode of ischemic stroke. Binary logistic regression was performed for multivariate analysis to assess the effect of risk factors that are associated with stroke (age, gender, tobacco use, alcohol, hyperlipidemia [HLD], atrial fibrillation/atrial flutter, hypertension [HTN], peripheral vascular disease [PVD], obesity, diabetes mellitus [for both type 1 and 2], drug use, previous history of venous thromboembolism, and SCD). Please note that "non-SCD” represents only the cases excluding SCD patients. For regression analysis of the "general population", both SCD and non-SCD patients are included. The results are statistically weighted. Results: 431,245 (0.36%) cases with SCD were identified from a total of 120,396,555 cases. The percentages are reported in ascending order of age by decade (18-30, 31-40, 41-50, 51-60, 61-70, 71-80; and 81 and above). The percentages of SCD cases with PMHS without deficits were 8.9, 9.1, 14.5, 8, 13.9, 14.3, and 21.2, respectively, while those for non-SCD cases were 0.3, 0.9, 3.1, 5.2, 7.1, 9.6, and 12.6 respectively. The percentages of SCD cases with PMHS with residual deficit were 1.6, 2.2, 2.8, 3.5, 5.1, 6.4, and 7.2, respectively, while those for non-SCD cases were 0.1, 0.3, 1.3, 2.4, 3.3, 3.7 and 3.7 respectively. The percentages of SCD cases with a new episode of an ischemic stroke were 2, 1.5, 1.9, 2.2, 3.8, 6.1, and 9.6, respectively, while those for non-SCD cases were 0.2, 0.5, 1.5, 2.3, 3.2, 4.3, and 4.7 respectively. The percentages of SCD cases with a new episode of hemorrhagic stroke were 0.1, 0.2, 0.3, 0.6, 0.8, 0.9, and 1.7, respectively, while those for non-SCD cases were 0.1, 0.2, 0.7, 0.8, 0.9, 1, and 1.1 respectively. The comparisons can be seen side by side in Table 1. Upon multivariate analysis of the general population to assess the effect of risk factors on PMHS, the remarkable odds ratios (OR) were: SCD with OR 5.24 (Confidence Interval 5.19-5.29, P<0.001) and HTN 2.19 (2.183-2.192, P<0.001). Multivariate analysis for a new episode of stroke in the general population showed that PMHS had an OR of 2.62 (2.61 - 2.63, P<0.001), HTN 1.745 (1.740-1.751, P<0.001), SCD 1.705 (1.67-1.74, P<0.001) and PVD 1.67 (1.65-1.70, P<0.001). On multivariate analysis for a new episode of stroke in SCD cases, notable results were PMHS with an OR of 7.47 (7.16-7.80, P<0.001), HTN 1.39 (1.32-1.46, P<0.001), HLD 1.58 (1.45-1.71, P<0.001), and tobacco use 1.25 (1.19-1.32, P<0.001). The OR for other risk factors can be reviewed in Table 2. Conclusion: The number of strokes in SCD increases with age. The difference between SCD and non-SCD groups is most pronounced in the younger population. This gap narrows in the fifth decade when the incidence of strokes rises in the general population. PMHS is strongly correlated with new episodes of stroke. Aggressive management of SCD in the younger population, along with optimal risk factor modification (control of diabetes, HTN, HLD, smoking avoidance/cessation) is desirable to decrease the risk of stroke. Further research in this direction is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

External Validation of the Saved Score for Venous Thromboembolism Risk Stratification in Patients with Multiple Myeloma Receiving Immunomodulatory Drugs

Background: High thrombogenicity is a well-established phenomenon in multiple myeloma (MM) and can lead to high morbidity and mortality. The risk of venous thromboembolism (VTE) is particularly elevated in the subset of MM patients treated with immunomodulatory drug (IMiD) containing regimens. The National Comprehensive Cancer Network (NCCN) and International Myeloma Working Group (IMWG) have implemented VTE risk assessment models, and recommend prophylactic anticoagulation based on individual patient, disease, or treatment-related factors specifically for MM patients receiving IMiD. With the recent incorporation of the SAVED (PMID 31319391) scoring system in the NCCN guidelines for VTE risk stratification, we sought to externally validate this risk assessment model and evaluate its predictive ability in our MM patient cohort. Methods: We retrospectively evaluated 501 adult patients with either newly diagnosed or relapsed/refractory MM who were newly initiated on an IMiD-based regimen between 2010 and 2019. Patients already on therapeutic or prophylactic anticoagulation were excluded from the study (aspirin was allowed). The SAVED score was calculated at IMiD initiation according to the following five parameters: surgery within last 90 days (+2), Asian race (-3), prior VTE history (+3), age ≥80 years (+1), dexamethasone use (+2 for high dose [>160 mg/30-day], or +1 for standard dose [120-160 mg/30-day]). Patients with SAVED scores of <2 and ≥2 were considered of low and high risk, respectively, for developing VTE after IMiD initiation. Time to VTE was estimated by Kaplan-Meier failure method. Logistic regression model was used to test components of the SAVED score with 1-year VTE status. Model discrimination was assessed via c statistic by calculating the area under the receiver operating characteristic curve (AUC) with bootstrapped 95% confidence interval (CI). Results: The median age of our cohort at the IMiD initiation was 64 years (range 34-89); 264 (53%) patients were male and 378 (75%) were white. IgG and IgA heavy chain subtypes were present in 280 (56%), and 105 (21%) patients respectively, whereas 110 (22%) patients had light chain disease only. The International Staging System (ISS) was I, II, III, and unknown for 161 (32%), 149 (30%), 136 (27%), and 55 (11%) of patients, respectively. Most patients (94%) received lenalidomide, whereas 14 (3%) and 15 (3%) patients were treated with thalidomide and pomalidomide, respectively. The distribution of SAVED covariates is shown in Table 1. The cumulative incidence of VTE at 12-month after IMiD initiation for the entire cohort was 16% (95% CI: 13-20%). Among the 84 patients who developed new VTE after IMiD initiation, 60 (71%) had lower extremity deep venous thrombosis (DVT), 10 (12%) had pulmonary embolism, 9 (11%) had both DVT and PE, and 5 (6%) had upper extremity DVT. The SAVED score stratified 112 patients (22%) as high-risk and 389 patients (78%) as low-risk (similar proportion as the original derivation study). Cumulative incidence of VTE at 6 and 12 months was 31% and 41% in the high-risk group, versus 6% and 9% in the low-risk group, respectively (Figure 1). Each point of SAVED score increase was associated with significantly higher chance of VTE within 1-year post IMiD initiation with excellent discrimination (odds ratio = 2.10 [95% CI 1.71-2.56], c statistic (AUC) = 0.76 [95% CI 0.70-0.81]). Conclusion: Our results successfully externally validated the SAVED model to predict IMiD-associated VTE in a real-life cohort of patients with MM. Patients with SAVED score of ≥2 had significantly higher incidence for VTE. This indicates that more aggressive pharmacologic thromboprophylaxis is needed in this specific patient population. The SAVED score outperformed several other similar VTE prediction models that were also validated in the current cohort (c statistic=0.68 for IMPEDE [PMID: 33997961] and 0.62 for PRISM [PMID: 35772005]). In contrast to other risk models that focused on all patients with MM, the SAVED score was derived and now validated specifically for patients starting IMiD as this it is the only cancer population with a strong guideline recommendation for ambulatory thromboprophylaxis. Future prospective validation would be useful to determine the predictive nature of SAVED while evaluating safety and efficacy of thromboprophylaxis with direct oral anticoagulant in high-risk patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 11728: Predictors of Secondary Pulmonary Hypertension-Related Hospitalizations and Subsequent Mortality in Adults With Obstructive Sleep Apnea

Background: Secondary pulmonary hypertension (SPH) is a predictor of poor outcomes in obstructive sleep apnea (OSA) patients. In this study, we examined sex/racial disparities, predictors and inpatient mortality in SPH-related hospitalizations among OSA patients. Methods: We used the National Inpatient Sample (2019) and ICD-10 codes to identify OSA-related hospitalizations with SPH. The burden of SPH and disparities by sex/race were assessed. We also compared the odds and predictors of in-hospital mortality in OSA patients with vs. without SPH. Results: Of total adult OSA hospitalizations (n=2317136, median age 66[56-74] years, males: 57.2%), 9.4% (218795/2317136) had SPH. Females vs Males (11.3% vs. 8.1%) and Blacks vs. other race groups (13.5%) with OSA had a higher prevalence of SPH [Fig. 1] . The SPH cohort often consisted of females (51 vs 41.9%), blacks (20.9 vs 14.0%), patients from lowest income quartile (29.7 vs 27.6%), Medicare insured (73.4 vs 60.6%), and non-elective admissions (89.2 vs 74.4%) vs. non-SPH cohort. SPH cohort also had a higher burden of complicated HTN (52.9 vs 36.3%), DM with complications (42.7 vs 32.4%), hyperlipidemia (59.4 vs 57.6%), COPD (52.5 vs 36.9%), history of prior MI (11.4 vs 9.6%) and venous thromboembolism (10.4 vs 8.4%). However, in-hospital mortality was more likely to be in males (OR 1.12 95%CI 1.00-1.25, p=0.048) vs Females, and OSA patients with metastatic cancer (OR 2.73 95%CI 2.04-3.65), solid non-metastatic tumors (OR 1.65 95%CI 1.26-2.15) (p&lt;0.001). Our analysis also showed black ethnicity, hyperlipidemia, obesity, tobacco use, and history of venous thromboembolism and TIA were protective against inpatient mortality in SPH-OSA patients. Conclusions: The prevalence of SPH with OSA was greater in females and blacks, whereas males and whites had higher subsequent inpatient mortality. More prospective studies are needed to understand the role of co-morbidities on survival outcomes.

Abstract 14693: Venous Thromboembolism in the Modern Era of Multiple Myeloma : An Analysis of Real-World Data From a Nationwide Claims Database in Japan

Introduction: Treatment for Multiple Myeloma (MM) with new therapeutic agents has dramatically improved outcomes and increased the number of survivors. Although venous thromboembolism (VTE) is common in MM, the pathophysiological interplay between VTE and MM, including risk factors related to the patient, disease, and modern treatments, is complex and incompletely understood. Objectives: To evaluate real-world data on the risk factors of VTE and outcomes of patients with MM using a nationwide claims database. Methods: This study involved the retrospective observational analysis of the Japan Medical Data Center (JMDC, Tokyo, Japan) database, an anonymized patient-level claims database younger than 75 years old. We identified cases with diagnosis and treatment of MM with codes provided by JMDC. Patients with a tentative diagnosis code of MM [C90] were included. Cases with a history of VTE or a pre-diagnostic history of fewer than six months were excluded. Propensity score (PS) was calculated using logistic regression based on age, gender, and cardiovascular risk factors. Results: We identified 2,023 eligible cases (mean age 53.6 ± 11.8 years) between January 2015 and December 2020. After 1:1 PS matching, the number of patients, mean age (years), follow-up (months) were as follows: MM group (n=280, 58.7 ± 8.1, 18.6 ± 14.8), Control group (n=280, 58.5 ± 8.1, 24.4 ± 18.4). Kaplan-Meier analysis indicated that the rate of VTE within 60 months was significantly higher among MM than in Control (25.7% vs 2.5%, Log-rank p&lt;.001). Within the MM group, multivariable Cox proportional hazard model showed that lenalidomide had a risk of VTE (Hazard Ratio 1.16 [95% Confidence Interval: 1.19-7.69]) among modern therapies (stem cell transplantation 37.1%, elotuzumab 6.4%, daratumumab 16.8%, bortezomib 88.9%, carfilzomib 21.8%, ixazomib 11.8%, thalidomide 3.9%, lenalidomide 78.9%, and pomalidomide 15.4%). Conclusions: Patients who underwent modern MM therapies, including immunomodulatory agents, had significantly higher VTE risk than PS-matched Control. Therefore, further studies using real-world data to improve prevention, early detection, and treatment of MM-related VTE are warranted.

Epidemiological Study Regarding the Incidence of Venous Thromboembolism in Patients After Cancer Remission.

The time course of reduction in the risk of venous thromboembolism (VTE) in patients who were diagnosed with cancer, treated with anticancer therapy, and in remission is unclear. We hypothesized that the risk of VTE will decrease over time after cancer remission. We conducted a retrospective analysis using claims data for cancer remission in Japan. Background information of patients who developed VTE after cancer remission was collected, and the VTE incidence rate after cancer remission was analyzed. Subgroup analysis based on VTE history, cancer type, and the presence or absence of surgery during hospitalization was conducted. A total of 638,908 patients were eligible for the analysis. VTE occurred in 5533 of 638,908 cases, pulmonary embolism occurred in 779 cases, and deep vein thrombosis occurred in 5084 cases after cancer remission. The mean age of patients who developed VTE was 70.1 ± 12.5years, and the proportion of men was 47.5%. All comorbidities and medications were higher in the VTE group (P < 0.001) than in the non-VTE group after cancer remission. The incidence of VTE was 2.4% per year in the first 30days, 1.35% per year in 31-60days, and gradually decreased to 0.48% per year in 181-360days, becoming almost constant (annual rate 0.3%) 2years after cancer remission. Risk of developing VTE decreased to the same level as that in patients without cancer 2years after cancer remission. Although the guidelines do not specify the duration of anticoagulant prophylaxis for new onset or recurrent VTE after cancer remission and the appropriate duration of such prophylaxis may vary depending on VTE risk factors, determining the period of high risk of VTE for each patient and preventing VTE is considered important.

A Thoracic Surgery–Specific Risk Assessment Model to Prevent Perioperative Venous Thromboembolism

BackgroundThe risk of venous thromboembolism (VTE) in patients undergoing resection in the setting of lung cancer represents a major challenge to improving postoperative outcomes. The Caprini risk assessment model has been validated in general surgery to determine a role for extended chemoprophylaxis to reduce VTE events. Our goal was to simplify this burdensome model for the unique needs of this thoracic surgical population to better guide anticoagulation decision-making. MethodsPatients who underwent a resection for lung malignant neoplasm at our institution between June 2005 and June 2013 with available 60-day postoperative follow-up data were evaluated. Exclusion criteria were long-term anticoagulation, inferior vena cava filter, missing data, and loss to follow-up. Twelve selected risk factors were analyzed for each patient by logistic regression with stepwise inclusion to model 60-day VTE incidence. ResultsThere were 225 patients eligible for inclusion, and a VTE incidence of 5.8% was observed. We generated a 5-variable model with predictive ability for VTE occurrence similar to that of the Caprini risk assessment model (P = .29). Weighting of sex, age, history of VTE, surgical approach, and duration of procedure provides a low-risk or high-risk composite score with 56% sensitivity and 77% specificity. ConclusionsIn this effort to model VTE incidence on the basis of a limited set of clinical risk factors, we demonstrated efficacy of retrospectively scoring patients with just 5 data points in anticipating risk of postoperative VTE. These high-risk surgical patients can be readily identified in the preoperative period to benefit from extended postoperative prophylaxis.

Circulating Endothelial Cells are Associated with Thromboembolic Events in Patients with Antiphospholipid Antibodies.

Endothelial damage has been described in antiphospholipid antibody (aPL)-positive patients. However, it is uncertain whether circulating endothelial cells (CECs)-which are released when endothelial injury occurs-can be a marker of patients at high risk for thrombosis. Ninety-seven patients with aPL and/or systemic lupus erythematosus (SLE) were included. CECs were determined by an automated CellSearch system. We also assayed plasma levels of tissue factor-bearing extracellular vesicles (TF+/EVs) and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) as markers of endothelial dysfunction/damage. Patients' mean age was 46.1 ± 13.9 years, 77 were women. Thirty-seven had SLE and 75 patients were suffering from antiphospholipid syndrome. Thirty-seven percent of patients presented a medical history of arterial thrombosis and 46% a history of venous thromboembolism (VTE). Thirteen patients had increased levels of CECs (>20/mL), with a mean CEC level of 48.3 ± 21.3 per mL. In univariate analysis, patients with obesity or medical history of myocardial infarction (MI), VTE, or nephropathy had a significant increased CEC level. In multivariate analysis, obesity (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 1.42-25.94), VTE (OR = 7.59 [95% CI: 1.38-41.66]), and MI (OR = 5.5 [95% CI: 1.1-26.6)] were independently and significantly associated with elevated CECs. We also identified significant correlations between CECs and other markers of endothelial dysfunction: sTREM-1 and TF+/EVs. This study demonstrated that endothelial injury assessed by the levels of CECs was associated with thromboembolic events in patients with aPL and/or autoimmune diseases.

Occurrence of Major Local Lower Limb Events in Type 2 Diabetic Patients with Lower Extremity Arterial Disease: Impact of Metformin

Patients with type 2 diabetes mellitus (T2DM) are particularly at risk of developing major adverse cardiovascular events (MACE) and peripheral artery disease (PAD) due to an acceleration of the atherosclerotic process linked to hyperglycemia and inflammation with a greater risk of local complications. We aimed to identify the predictive factors for major adverse limb events (MALE) in T2DM patients with PAD to manage modifiable factors at an early stage. This is a prospective study in which T2DM patients with PAD were included from November 2017 to May 2018 and followed over 12months. The predictive factors for the onset of MALE, MACE, and death from all causes have been identified. A total of 100 patients were included; 37% of the patients developed a MALE. After multivariate analysis, metformin was associated with a decrease of MALE (odds ratio (OR)=0.26; 95% confidence interval (CI) [0.10; 0.68]; P=0.007), and a history of the treatment of intravenous iloprost was associated with an increased risk of MALE (OR=5.70; 95% CI [1.31; 31.93]; P=0.029). Regular physical activity was associated with a decreased risk of MACE (OR=0.07; 95% CI [0; 0.44]; P=0.021). A history of stroke and a history of venous thromboembolism were associated with an increased all-cause mortality risk with OR=3.68; 95% CI [1.17; 11.5]; P=0.025 and OR=3.78; 95% CI [1.16; 12.3]; P=0.027. Metformin is protective against local complications in people with diabetes with PAD and should be prescribed to diabetic patients with PAD at an early stage.

Cardiovascular risks associated with Janus kinase inhibitors: peering outside the black box.

Considerable controversy related to the cardiovascular safety of Janus kinase inhibitors (JAKinibs) has arisen following the results of the ORAL Surveillance trial. In this trial of rheumatoid arthritis (RA) ≥ 50years with at least one prevalent cardiovascular disease (CVD) risk factor, tofacitinib was not found to be non-inferior to tumour necrosis factor-alpha inhibitors (TNFi) with regards to the risk for major adverse cardiovascular events (MACE), venous thromboembolism (VTE) or malignancy. Following the results of ORAL Surveillance, the United States Food and Drug Administration (US FDA) issued a boxed warning regarding increased risks of MACE, VTE and malignancy with tofacitinib, baricitinib or upadacitinib in inflammatory arthritis or ulcerative colitis. Analysis of data from other trials (including long-term follow-up studies) of tofacitinib in RA, psoriasis, psoriatic arthritis, spondyloarthritis and inflammatory bowel diseases suggests an overall similar risk of MACE or VTE with tofacitinib when compared with TNFi. In specific patient populations with risk factors for or prior history of MACE or VTE, the risk of subsequent MACE or VTE with tofacitinib use is considerably heightened. Post-hoc analyses from ORAL Surveillance presented at the recent EULAR meeting further help to delineate patients with RA at increased risk of MACE/VTE with tofacitinib. Based on the available literature from trials and long-term follow-up studies of baricitinib and upadacitinib, there exists insufficient evidence to extend the warning of MACE/VTE with tofacitinib to these drugs. Ongoing post-marketing surveillance studies of JAKinibs in immune-mediated inflammatory diseases should help clarify CVD risk with JAKinibs.

Obstructive Sleep Apnea Is Associated with Serious Complications But Not Increased Mortality Following Elective Bariatric Surgery: a Retrospective Cohort Study of 751,952 Patients.

The aim of the study was to characterize the prevalence of obstructive sleep apnea (OSA) in elective bariatric surgery patients and to determine if OSA is an independent predictor of 30-day serious complications and 30-day mortality among bariatric surgery patients. An analysis of the MBSAQIP database from 2015 to 2019 was conducted, and patients were stratified by OSA diagnosis. Data was extracted on patient age, sex, race, and comorbidities. A multivariate logistic regression model was created to evaluate the impact of OSA on 30-day serious complications and 30-day mortality. Of 751,952 patients, 287,180 (38.2%) were identified as having OSA. OSA patients were older (48.0 ± 11.4 vs. 42.2 ± 11.9years; p < 0.0001) and were of increased BMI (46.5 ± 8.5kg/m2vs. 44.6 ± 7.3kg/m2; p < 0.0001). OSA was not associated with 30-day mortality in the multivariable logistic regression model (OR 0.98, 95% CI 0.83-1.16; p = 0.829). OSA was associated with increased odds of 30-day serious complications (OR 1.33, 95% CI 1.30-1.36; p < 0.0001). In addition, dialysis (OR 3.07, 95% CI 2.68-3.52; p < 0.0001), positive venous thromboembolism history (OR 2.46, 95% CI 2.32-2.60; p < 0.0001), and oxygen dependence (OR 2.42, 95% CI 2.18-2.68; p < 0.0001) were all identified as major predictors of serious complications. We identified OSA as a modifiable factor predictive of serious complications following elective bariatric surgery. OSA is highly prevalent in this patient population, and it appears to be an important risk factor that deserves further attention in terms of peri-operative optimization strategies.

Immediate and delayed complications of inferior vena cava filters

ObjectiveInferior vena cava (IVC) filter placement has increased dramatically in the past two decades. However, literature supporting the efficacy of these devices has been limited and controversial. In the present study, we have evaluated the predictors and rates of technical complications after IVC filter insertion in a large national database. MethodsThe Vascular Quality Initiative registry was explored (January 2013 to December 2020). Immediate complications were defined as venous injury requiring treatment, filter misplacement (failure to open, deployed >20 mm from intended site or in wrong vein, embolized to the heart), angulation >20°, and insertion site complications. Delayed complications were defined as migration, angulation >15°, fracture, caval and/or iliac thrombosis, filter thrombus, fragment embolization, and perforation. The Pearson χ2 test was used to compare the baseline characteristics between the patients who had developed immediate and/or delayed complications and those who had not. The predictors of these complications were evaluated using multivariable logistic regression, Cox proportional hazard regression, and Kaplan-Meier survival analysis. ResultsA total of 14,784 patients were included in the present analysis, with a median follow-up of 11 months (interquartile range, 4-16 months). The rate of immediate and delayed complications was 1.8% and 3.1%, respectively. Angulation (1.2%) was the most common immediate complication, and filter thrombosis (1.6%) was the most common delayed complication. Compared with the patients with no immediate complications, those with immediate complications were more likely to have had abnormal anatomy (6.0% vs 1.7%; P < .001) and a landing zone other than infrarenal (7.0% vs 4.2%; P = .02). Compared with their counterparts, those with delayed complications were less likely to have received statins (21.0% vs 29.5%; P = .006) and were more likely to have a family history of venous thromboembolism (8.0% vs 5.1%; P = .047). Logistic regression analysis revealed that renal vein visualization was associated a 50% reduction (adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.27-0.92; P = .027) in the odds of immediate complications and female sex and abnormal anatomy were associated with a 41% (aOR, 1.41; 95% CI, 1.08-1.85; P = .013) and 244% (aOR, 3.44; 95% CI, 1.66-7.16; P < .001) increase in the odds of immediate complications, respectively. Immediate (P = .21) and delayed (P = .51) complications did not result in increased mortality. ConclusionsThe immediate and delayed IVC filter complication rates were 1.8% and 3.1%, respectively, but the occurrence of complications was not associated with increased mortality. Female sex was associated with an increase in the development of immediate complications. The incidence of immediate complications might be mitigated if advanced imaging were used for renal vein visualization before IVC filter deployment. Delayed complications might be avoided if IVC filter retrieval were performed in a timely fashion and institutional retrieval protocols were optimized.

Determination of four homogeneous subgroups of patients with antiphospholipid syndrome: a cluster analysis based on 509 cases.

APS is a heterogeneous disease with different phenotypes. Using an unsupervised hierarchical cluster analysis, we aimed to determine distinct homogeneous phenotypes among APS patients. We performed an observational, retrospective study of APS patients enrolled in the French multicentre 'APS and SLE' registry who met the Sydney classification criteria. The clustering process involved an unsupervised multiple correspondence analysis followed by a hierarchical ascendant clustering analysis; it used 27 variables selected to cover a broad range of APS clinical and laboratory manifestations. These analyses included 509 patients, mainly women (77.8%). Mean (s.d.) age at APS diagnosis was 36.2 (14.6) years, and mean follow-up since diagnosis 10.3 (8.5) years. This hierarchical classification cluster analysis yielded four homogeneous groups of patients: cluster 1, mostly with venous thromboembolism without any associated autoimmune disease; cluster 2, older, lowest proportion of women, history of arterial events, and/or with migraines, arterial hypertension, diabetes mellitus, or dyslipidaemia; cluster 3, younger, highest proportion of women, associated SLE or other autoimmune diseases, and a history of venous thromboembolism or pregnancy morbidity; and cluster 4, mainly with a history of catastrophic antiphospholipid syndrome, aPL-associated nephropathy, and pregnancy morbidity, with frequent triple positivity and more deaths (16.7%). Our study applied an unsupervised clustering method to distinguish four homogeneous APS patient subgroups that were predominantly venous; arterial; associated with SLE or another autoimmune disease; and arterial microthrombotic. Heterogeneous pathophysiological mechanisms may explain these findings.

Acute pulmonary embolism: in hospital outcome from a prospective observational registry (M-PER) from a low-and middle-income country

Abstract Background Acute Pulmonary embolism the third most common cause of cardiovascular death in the world. Despite the large burden of acute pulmonary embolism, there is a paucity of prospective data from low-and middle-income countries. Purpose To study the clinical characteristics, treatment strategies employed, in-hospital outcome, one-year follow up results, and the prognostic factors in patients with acute pulmonary embolism from a low-and middle-income country. Methods All consecutive patients diagnosed with and treated for acute pulmonary embolism at our institution from November 2016 to November 2021 were included in the registry. Pulmonary embolism was diagnosed using clinical features (Wells' criteria of ≥3) supported by either CT angiogram or echocardiogram. Detailed history, clinical examination, preliminary basic blood investigations, cardiac troponins along with coagulation workup, ECG and ECHO were done for all patients. Patients were classified as having massive or high risk, submassive or intermediate risk and low risk pulmonary embolism based hemodynamic status, sPESI score, echocardiogram and cardiac troponins. Treatment was at the discretion of treating physician. In general, all patients with massive pulmonary embolism were considered for thrombolysis. All patients received anticoagulation with unfractionated heparin. Outcomes included hospital lengths of stay, all-cause in-hospital mortality and one year mortality Results 186 patients with acute pulmonary embolism were prospectively enrolled during period. 62% were male. Mean age was 42.38±13.4 years. The risk factors noticed include prior history of venous thromboembolism, active malignancy, recent surgery, trauma, immobilisation, diabetes, hypertension, and chronic obstructive pulmonary disease in 18%, 5%, 10%, 8%, 14%, 17%, 10% and 3% of our patients respectively. Shortness of breath (98%), chest pain (37%), leg swelling (37%), cough (33%), shock (27%), syncope (15%) and haemoptysis (12%) were the reasons for presentation. Sinus tachycardia was the commonest finding (80%). Right ventricular (RV) strain pattern was present in 68%, S1Q3T3 pattern in 56% and RBBB in 32%. RV dilatation was present in 93% and RV dysfunction in 75%. Thrombus was visualised in the pulmonary artery in 37% and right heart chambers in 12% (714). 26% were classified as high risk, 60% as intermediate risk and 13.4% as low risk acute pulmonary embolism. Overall 50% (92% of high-risk and 41% of intermediate risk) patients received fibrinolytic therapy. In hospital mortality was 16% (29 patients) of which 72% were from high-risk group. In the high-risk group those who were fibrinolysed had a lower mortality compared to those not lysed. (75% vs 40%). This difference was not observed in the intermediate risk group. Conclusion Acute pulmonary embolism is a disease with high in-hospital mortality. Fibrinolytic therapy with streptokinase has a lifesaving potential in high risk patients. Funding Acknowledgement Type of funding sources: None.