Odds Of Venous Thromboembolism Research Articles

Outcomes Following Total Hip Arthroplasty in Patients Who Have Von Willebrand Disease Depend on Postoperative Anticoagulation

BackgroundVon Willebrand disease (VWD) is the most common congenital bleeding disorder. This autosomal dominant condition arises from quantitative or qualitative defects of Von Willebrand factor. To our knowledge, this study leveraged a national database to characterize the largest VWD cohort of total hip arthroplasty (THA) patients to date, assessing 90-day postoperative adverse events and 5-year revision-free survival. MethodsAdult patients who underwent primary THA for osteoarthritis were identified from January 2010 to October 2021 in a nationwide database. Patients who had and did not have VWD were matched (4:1) on age, sex, and Elixhauser Comorbidity Index and compared with multivariable logistic regression. Patients were then categorized based upon venous thromboembolism (VTE) chemoprophylaxis prescription patterns to compare bleeding and thrombotic adverse events. ResultsOf 544,851 THA patients, VWD was identified in 309 patients (0.06%). The matched cohorts contained 1,221 patients who did not have VWD and 306 patients who have VWD. On multivariable analysis, VWD patients had increased odds of 90-day VTE (odds ratio [OR] = 1.86) and hematoma (OR = 3.40) (P < .05 for all). No difference in 5-year revision-free survival was found. The VWD patients receiving aspirin or no prescriptions had greater odds of VTE (OR = 2.39, P = .048). Those on other chemoprophylaxis agents had greater odds of hematoma (OR = 4.84, P = .006). ConclusionsPatients with VWD undergoing THA had increased odds of 90-day VTE if using aspirin or no prescriptions, or hematoma if using other chemoprophylaxis. There is a delicate balancing act of clotting versus bleeding that must be considered in managing such patients, but it was reassuring that no difference in overall 5-year revision-free survival was found.

Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a &gt;6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P &lt;.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P &lt;.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, $1280; HF, $2677) and readmission (COPD, $379; HF, $1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.

Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure.

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a >6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P <.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P <.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, 2677) and readmission (COPD, 1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.

Risk factors and mortality associated with venous thromboembolism in the elderly US population with acute lymphocytic leukemia

ObjectiveThe purpose of our study was to examine risk factors for venous thromboembolism (VTE) and VTE associated mortality in elderly acute lymphocytic leukemia (ALL) patients receiving different treatment options. MethodsWe analyzed data from the United States SEER-Medicare database (2007–2015) for patients ≥65 years diagnosed with ALL. Data were stratified by treatment options into three groups as chemotherapy: the use of antimetabolites, anthracyclines, alkylating agents or vinca alkaloids; other treatment: the use of corticosteroids/tyrosine kinase inhibitors without chemotherapy; and no treatment. Logistic regression was used to examine risk factors for VTE and Cox proportional regression was used to evaluate Hazard Ratios (HRs) for the effect of VTE on mortality in ALL patients. ResultsIn a cohort of 1088 elderly ALL patients, 17.4 % patients had a diagnosis of VTE. VTE was diagnosed in 27.7 % of 159 patients who received chemotherapy, 16.2 % of 328 patients who received other treatment, and 15.3 % of 601 patients who did not receive any treatment (p < 0.001). Adjusted odds of VTE were 1.59 (95 % CI, 1.02–2.48) in patients who received chemotherapy, and ORa = 0.88 (95 % CI, 0.60–1.30) in those who received other treatment, compared to those who did not receive any treatment. VTE was not associated with the risk of death in ALL patients (HRa = 0.85, 95 % CI, 0.70–1.02). ConclusionOur study identified VTE risk factors and the effect of VTE on mortality in elderly ALL patients with and without treatment.

Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy

Although hormone therapy (HT) in perimenopausal women is associated with increased risk for venous thromboembolism (VTE), it is unclear to what extent statins may mitigate this HT-associated risk. To estimate VTE risk in women aged 50 to 64 years taking HT with or without statins. This nested case-control study analyzed data from a commercially insured claims database in the US. Eligible participants included women aged 50 to 64 years with at least 1 year of continuous enrollment between 2008 and 2019. Data analysis occurred from January 2022 to August 2023. Filled prescriptions for estrogens, progestogens, and statins were recorded in the 12 months prior to index. Recent HT was defined as any estrogen or progestogen exposure within 60 days before the index date. Current statin exposure was defined as 90 or more days of continuous exposure prior to and including the index date. Statin intensity was defined by the statin exposure 30 days prior to index. Cases were identified with VTE diagnoses (diagnostic codes) preceded by at least 12 months without VTE and followed within 30 days by anticoagulation, an inferior vena cava filter placement, or death. Controls were matched to cases (10:1) on date and age. Conditional logistic regression models estimated risk for HT and statin exposures with odds ratios (OR), adjusted for comorbidities. Conditional logistic regression models were used to estimate VTE risk for HT and statin exposures with odds ratios (ORs), adjusted for comorbidities. Intensity of statin therapy was measured as a subgroup analysis. The total sample of 223 949 individuals (mean [SD] age, 57.5 [4.4] years) included 20 359 cases and 203 590 matched controls. Of the entire sample, 19 558 individuals (8.73%) had recent HT exposure and 36 238 individuals (16.18%) had current statin exposure. In adjusted models, individuals with any recent HT exposure had greater odds of VTE compared with those with no recent HT exposure (OR, 1.51; 95% CI, 1.43-1.60). Individuals receiving current statin therapy had lower odds of VTE compared with those with no current statin exposure (OR, 0.88; 95% CI, 0.84-0.93). When compared with those not recently taking HT or statins, the odds of VTE were greater for those taking HT without statins (OR, 1.53; 95% CI, 1.44-1.63) and for those taking HT with statins (OR, 1.25; 95% CI, 1.10-1.43), but were lower for those taking statins without HT (OR, 0.89; 95% CI, 0.85-0.94). Individuals taking HT with statin therapy had 18% lower odds of VTE than those taking HT without statins (OR, 0.82; 95% CI, 0.71-0.94) and there was greater risk reduction with higher intensity statins. In this case-control study, statin therapy was associated with reduced risk of VTE in women taking HT, with greater risk reduction with high-intensity statins. These findings suggest that statins may reduce risk of VTE in women exposed to HT and that HT may not be contraindicated in women taking statins.

Venous Thromboembolism (VTE) in Post-CAR-T Patients - a Meta-Analysis of Phase 2 &amp; 3 Clinical Trials

Introduction: Chimeric Antigen Receptor T- cells (CAR-T) therapy is genetically engineered T cells that provide durable responses for patients with certain hematological malignancies. CAR-T therapy continues to expand as a treatment option for various malignant conditions. ICANS and CRS, a clinical syndrome of neurological symptoms, fever, hypotension, and hypoxia, are potentially serious complications of post-CAR-T. Both of these complications can, in turn, increase the risk of VTE. Only a few case reports and retrospective analyses have described the risk of VTE. The primary objective of this systematic review and meta-analysis is to review the data from phase 2 and 3 clinical trials to determine the incidence and risk of VTE post-CAR-T treatment. Material and methods: The National Institute of Health (NIH) library, Cochrane Library, and ClinicalTrials.gov database were scoured for all phase 2 and phase 3 clinical trials, completed by March 7, 2023, on CAR-T cell therapy. Two reviewers independently verified the results. Several data points were extracted. A biostatistician conducted the meta-analysis using the Meta package in the R version 4.1.2 (Balduzzi, Rücker, &amp; Schwarzer, 2019; R Core Team, 2021). The endpoints of interest were the odds ratio and relative risk of developing VTE while in CRS using the Mantel-Haenszel method. Result: Nine phase 2 &amp; 3 trials (Seven phase 2 and two phase 3 trials) were identified and were included in our study. The incidence of CRS, ICANS, and VTE was obtained from the toxicity list and supplemental data for analysis. Only KTE-X19 studying Brexucabtagene (Tecartus) for relapsed or refractory adult B-cell acute lymphoblastic leukemia and Relapsed or refractory Mantle-Cell Lymphoma mentioned the incidence of one and three cases of VTE, respectively, in patients getting CAR-T cell therapy. The total number of patients reviewed from these studies was 1784, of which 1017 received CAR-T cell therapy. The odds of VTE were 99.9995% lower than CRS, OR = 0.0005, 95% CI [0.0001, 0.0017] in patients receiving a CAR-T infusion, p &amp;lt; .0001. The Relative risk of VTE was 0.0050, 95% CI [0.0019, 0.0132]. The test of heterogeneity (p = .0430) suggests the presence of heterogeneous results. The heterogeneity statistic I2 is 49.86%, indicating moderate heterogeneity (percentage of variation across studies due to heterogeneity rather than chance). The odds of VTE were 99.9999% lower than no VTE, OR = 0.0001, 95% CI [0.0001, 0.0004], p &amp;lt;.0001 with a Relative risk of 0.0039, 95% CI [0.0015, 0.0105]. Discussion: CRS is a known risk factor for VTE. In patients with underlying malignancy undergoing CAR-T therapy, the risk can be much higher than those without malignancy who develop CRS for other reasons. In a retrospective single-center observational study, Hashmi et al. reported an 11% incidence of VTE in lymphoma patients treated with CAR-T directed against the CD-19 receptor. Our systematic review and metanalysis didn't find a statistically increased risk of VTE in the patients getting CAR-T cell therapy despite the risk of CRS/ ICANS and underlying malignancy. The findings suggest that the thrombotic risks are either low or were not reported in the interval specified in the studies. The need for thromboprophylaxis must be made on a case-by-case basis, factoring in other risk factors such as underlying disease, cytopenia, and other medical comorbidities. Conclusion: The Incidence of VTE is low following CAR-T therapy despite the risks, and the need for thromboprophylaxis should be based on individual patient characteristics. Patient selection, exclusion criteria, and short follow-up periods following phase 2 trials might impact our study results. In a long-term phase 3 trial, collecting data for VTE may be needed to appropriately stratify patients for their VTE risk so that an appropriate thromboprophylaxis can be recommended to prevent an additional serious complication post-CAR-T.

Inherited Thrombophilia Gene Mutations and Risk of Venous Thromboembolism in Cancer: A Systematic Review and Meta-Analysis

Inherited thrombophilia and cancer are both recognized risk factors for venous thromboembolism (VTE). In the general population, the risk of thrombosis is increased in patients with inherited thrombophilia, but the role of inherited thrombophilia on the risk of cancer-associated VTE remains controversial. The objective of this study was to summarize and determine whether cancer patients with inherited thrombophilia gene mutations have an increased risk of developing VTE. We conducted a systematic literature search in Medline, EMBASE and Cochrane Central databases, as well as references of included studies from inception until September 26 th 2022. We included observational (cohort or case-control) and interventional studies comprising of human adult cancer patients who were tested for any inherited thrombophilia gene mutation. The outcome was objectively confirmed symptomatic or asymptomatic first VTE (upper or lower limbs deep vein thrombosis, pulmonary embolism, and/or splanchnic or cerebral vein thrombosis) occurring after a cancer diagnosis. Two reviewers independently screened the titles/abstracts and full texts of all potentially eligible articles. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using Mantel-Haenszel random-effects models. We used the Quality in Prognostic Studies (QUIPS) risk of bias tool to assess study risk of bias. A total of 4274 studies were screened for eligibility. Thirty-six studies involving different cancer types and treatments were included in the systematic review, of which 28 studies were included in the meta-analysis (Figure 1). Among studies included in the meta-analysis, 9 studies included various cancer types while the remaining 19 studies were in selected cancer types (3 lung, 3 myeloma, 2 brain, 2 bladder, 2 breast, 2 gynecologic, 1 testicular, 1 lung or gastrointestinal, 1 pancreas, 1 colorectal and 1 breast or gastrointestinal). There were 18 cohort (11 prospective and 7 retrospective) and 10 case-control studies. The following seven inherited thrombophilia gene mutations were meta-analyzed: ABO blood type, Factor V Leiden (FVL), Methylenetrahydrofolate Reductase (MTHFR) C677T, Plasminogen-Activator Inhibitor-1 (PAI-1) 4G/5G, Prothrombin Factor II G20210A, Vascular Endothelial Growth Factor (VEGF) C634G and VEGF C2578A. In cancer patients with non-O blood types, FVL and Prothrombin Factor II G20210A mutations, the risk of VTE was significantly increased with ORs of 1.56 (95% CI: 1.28-1.90), 2.28 (95% CI: 1.51-3.48) and 2.14 (95% CI: 1.14-4.03), respectively, compared to patients with O blood and wild types (Table 1). In addition, heterozygous and homozygous MTHFR C677T were associated with ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively (Table 1). Among those with heterozygous and homozygous PAI-1 4G/5G, VEGF C634G and VEGF C2578A, no significant increase in the odds of VTE and moderate to considerable heterogeneity were observed (Table 1). Few studies had low risk of bias, except for studies of ABO blood group, which predominantly had low risk of bias. In conclusion, this meta-analysis provides evidence that non-O blood type, FVL, Prothrombin Factor II G20210A and heterozygous MTHFR C677T significantly increase the risk of VTE in cancer patients. However, there is moderate to high risk of bias in the currently available data, further well-designed studies are needed.

The efficacy and safety of direct oral anticoagulants compared with low-molecular-weight heparin for venous thromboembolism prophylaxis after surgical resection of primary lower extremity bone or soft-tissue sarcoma.

The incidence of postoperative venous thromboembolism (VTE)and wound complications is greater after sarcoma resection. We sought to identify differences in postoperative VTE and bleeding complications with direct oral anticoagulants (DOACs)versus low-molecular-weight heparin (LMWH)following resection of lower extremity primary bone or soft tissue sarcoma. We retrospectively identified 2083 patients from the PearlDiver database who underwent resection of primary bone or soft tissue sarcoma of the lower extremity from January 2010 to October 2021 and prescribed LMWH or DOAC within 90-days postoperatively. The primary outcomes were comparison of postoperative incidence and odds of deep venous thrombosis(DVT), pulmonary embolism(PE), and bleeding complications within 90-days following resection. Patients prescribed DOACs had a greater odds of DVT (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.06-2.41;p = 0.024) and PE (OR: 3.38;95% CI: 1.96-5.86;p < 0.001) within 90-days following resection of bone sarcoma when compared withthe LMWH cohort. Patients undergoing resection of soft tissue sarcomas also had greater odds DVT (OR: 1.65;95% CI: 1.09-2.49;p = 0.016) and PE (OR: 2.62;95% CI: 1.52-4.54;p < 0.001) in the DOAC cohort. There was no difference in the odds of bleeding complications. This study demonstrated an increased incidence and odds of VTE, but not bleeding complications, when using DOACs versus LMWH after primary bone or soft tissue sarcoma resection. Level III.

Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation

BackgroundPrevious cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.ResultsOur findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.ConclusionOur study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

D-dimer predicts venous thromboembolism in multiple myeloma: a nested case-control study

BackgroundClinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment. ObjectivesWe sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM. MethodsWe identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE. ResultsEach 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; c-statistic 0.61; 95% CI 0.51-0.71). There was no association between sP-selectin and VTE. Each one increase in natural log of D-dimer was associated with a 44% increase in odds of VTE, so we assigned points (ranging from −2 to +2) to D-dimer values and incorporated them into IMPEDE VTE, forming IMPEDED VTE. There was a 30% increase in odds of VTE per each 1-point increase in IMPEDED VTE (OR 1.30; 95% CI 1.12-1.52; c-statistic 0.65; 95% CI 0.55-0.75). ConclusionAmong patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE—IMPEDED VTE—could improve prediction of VTE among patients with MM.

Venous Thromboembolism: Assessing Risk Factors in Elective Foot and Ankle Surgery Patients

Category: Midfoot/Forefoot; Ankle Introduction/Purpose: Venous thromboembolism (VTE) after foot and ankle surgery is a significant concern for patients and surgeons. The absence of guidelines for thromboprophylaxis in elective procedures underscores the importance of understanding risk factors. This study aimed to identify key risk factors of VTE in patients who underwent elective foot and ankle surgery, analyzing the rates based on the anatomical location of the surgery and the post-operative period. Methods: Data was collected from IBM MarketScan Database (2009-2019) for patients &gt;18y without prior VTE who underwent elective foot/ankle surgery. Patients were divided into three groups based on region of surgery (forefoot, mid/hindfoot, lower leg/ankle), and VTE incidence was recorded 30- and 90-days post-surgery. Risk factors for VTE were identified through multivariate logistical regression analysis. Results: Among the 301,256 patients who underwent elective foot and ankle surgeries, the overall incidence of VTE within 90 days was 0.95%. The findings revealed that 31.8% of VTE incidents occurred within the first two weeks after surgery, and 29.2% still occurred after 6 weeks. An analysis of the anatomical region of surgery demonstrated that the lowest rate of VTE was amongst patients undergoing forefoot surgery (0.70%). There was a higher incidence and risk for VTE in patients undergoing midfoot/hindfoot surgery (1.22%, OR = 1.75) and lower leg/ankle surgery (1.76%, OR= 2.53). Additional risk factors for VTE included thrombophilia (OR = 5.06), male sex (OR = 1.43), increasing age (OR &gt; 1.25), and a high Charlson Comorbidity Index (OR &lt; 0.82 for scores &lt; 5). Conclusion: This study identifies the incidence and timing for VTE after elective foot and ankle surgery. Furthermore, this study defines the risk factors associated with increased odds of VTE after elective foot and ankle surgeries. These findings are helpful in educating patients about a continued risk for VTE throughout the 90-day postoperative period. These results can also be utilized to stratify patients who need thromboprophylaxis based on the individual risk level.

Prior COVID-19 and Venous Thromboembolism Risk in Total Joint Arthroplasty in Patients Over 65 Years of Age

BackgroundThe COVID-19 pandemic has been associated with increased risks of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). However, there is limited literature investigating prothrombotic states and complications after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We investigated (1) trends in VTE, PE, and DVT rates post-THA and TKA from 2016 to 2019 compared to 2020 to 2021 and (2) associations between prior COVID-19 diagnosis and VTE, PE, and DVT. MethodsA national dataset was queried for elective THA and TKA cases from 2016 to 2021. We first assessed trends in 90-day VTE prevalence between 2016 to 2019 and 2020 to 2021. Second, we investigated associations between previous COVID-19 and 90-day VTE with regression models. ResultsFrom 2016 to 2021, a total of 2,422,051 cases had an annual decreasing VTE prevalence from 2.2 to 1.9% (THA) and 2.5 to 2.2% (TKA). This was evident for both PE and DVT (all trend tests P < .001). After adjusting for covariates (including vaccination status), prior COVID-19 was associated with significantly increased odds of developing VTE in TKA patients (odds ratio 1.2, 95% confidence interval 1.1 to 1.4, P = .007), but not DVT or PE (P > .05). There were no significant associations between prior COVID-19 and VTE, DVT, or PE after THA (P > .05). ConclusionsOur study suggests that a previous diagnosis of COVID-19 is associated with increased odds of VTE, but not DVT or PE, in TKA patients. Ongoing data monitoring is needed given our effect estimates, emerging COVID-19 variants, and evolving vaccination rates.

Trends and predictions of perioperative transfusion and venous thromboembolism in hepatectomy using a North American Registry.

Studies indicate a link between allogeneic blood transfusion and venous thromboembolism (VTE) post-major surgery. Analyzing trends and predictors of these outcomes after hepatectomy can inform risk management. The American College of Surgeons National Surgical Quality Improvement Program database was used for a retrospective analysis. Primary outcomes were perioperative red blood cell (RBC) transfusion and VTE events within 30 days of hepatectomy. Seven-year trends and predictors were evaluated. Among 29,131 hepatectomy patients, transfusion rates showed no statistically significant decreasing trends (p = .122) from 2014 to 2020 (18.13%-16.71%), while VTE rates showed a downward trend over the 7 years (p = .021); 17.2% received RBC transfusion, with higher rates in surgeries lasting ≥282 min (median: 220 min). Calculated RBC mass [hematocrit (%) × body weight (kg) × 10-5 × 70/ (body mass index/22)] at or below 1.5 L substantially increased transfusion odds. VTE was reported postoperatively in 2.6% of cases more frequently in longer cases involving transfusions. The adjusted odds ratio (aOR) of VTE escalated from the shortest operative time to the longest (3.17; 95% confidence interval [CI], 2.37-4.22). The adjusted odds of VTE doubled for transfused patients compared to non-transfused patients (aOR, 2.19; 95% CI, 1.86-2.57). Rates of RBC transfusion and VTE rates hepatectomy have minimally changed in the recent years. VTE prevention is challenging in extended surgeries at increased risk of bleeding and RBC transfusions. Patient-level data on coagulation and thromboprophylaxis can potentially refine risk assessment for postoperative VTE.

Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy

BackgroundInherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear. ObjectivesOur objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy. MethodsWe conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated. ResultsOf the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding. ConclusionOur results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

Venous Thromboembolism After Abdominal and Minimally Invasive Large Specimen Hysterectomy

To investigatethe incidence of venous thromboembolism (VTE) in patients undergoing large specimen hysterectomy for benign indications. To evaluate the impact of route of surgery and operative time in the development of VTE in this population. Retrospective cohort study (Canadian Task Force Classification II2) of targeted hysterectomy data prospectively collected from the American College of Surgeons National Surgical Quality Improvement Program involving over 500 hospitals across the United States SETTING: National Surgical Quality Improvement Program Database PATIENTS: Women aged 18 years or older undergoing hysterectomy for benign indications between 2014 and 2019. Patients were further classified into four groups according to uterine weight: <100g, 100-249g, 250g-499g, and specimens ≥500g. Current Procedural Terminology codes were used to identify cases. Variables including age, ethnicity, body mass index, smoking status, diabetes, hypertension, blood transfusion, and American Society of Anesthesiologists classification system scores were collected. Cases were stratified by route of surgery, operative time, and uterine weight. A total of 122,418 hysterectomies occurring between 2014-2019 were included in our study, of which 28,407 (23.2%) patients underwent abdominal, 75,490 (61.7%) laparoscopic, and 18,521 (15.1%) vaginal hysterectomy. The overall rate of VTE in patients with large specimen hysterectomies (≥500g) was 0.64%. After multivariable adjustment, there was no significant difference in the odds of VTE between uterine weight groups. Only 30% of the surgeries with uterine weight above 500g were performed with minimally invasive surgical routes. Patients who underwent minimally invasive hysterectomy had lower odds of VTE via laparoscopic (aOR 0.62; CI:0.48-0.81) and vaginal (aOR 0.46; CI:0.31-0.69) routes compared to laparotomy. Prolonged operative time (>120 min) was associated with an increased odds of VTE (aOR 1.86; CI:1.51-2.29). The occurrence of VTE after benign large specimen hysterectomy is rare. The odds of VTE is higher with longer operative times and lower with minimally invasive approaches even for markedly enlarged uteri.

Effectiveness, safety, and costs of thromboprophylaxis with enoxaparin or unfractionated heparin in inpatients with obesity.

Obesity is a frequent and significant risk factor for venous thromboembolism (VTE) among hospitalized adults. Pharmacologic thromboprophylaxis can help prevent VTE, but real-world effectiveness, safety, and costs among inpatients with obesity are unknown. This study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH). A retrospective cohort study was performed using the PINC AI™ Healthcare Database, which covers more than 850 hospitals in the United States. Patients included were ≥18 years old, had a primary or secondary discharge diagnosis of obesity [International Classification of Diseases (ICD)-9 diagnosis codes 278.01, 278.02, and 278.03; ICD-10 diagnosis codes E66.0x, E66.1, E66.2, E66.8, and E66.9], received ≥1 thromboprophylactic dose of enoxaparin (≤40 mg/day) or UFH (≤15,000 IU/day) during the index hospitalization, stayed ≥6 days in the hospital, and were discharged between 01 January 2010, and 30 September 2016. We excluded surgical patients, patients with pre-existing VTE, and those who received higher (treatment-level) doses or multiple types of anticoagulants. Multivariable regression models were constructed to compare enoxaparin with UFH based on the incidence of VTE, pulmonary embolism (PE)---------related mortality, overall in-hospital mortality, major bleeding, treatment costs, and total hospitalization costs during the index hospitalization and the 90 days after index discharge (readmission period). Among 67,193 inpatients who met the selection criteria, 44,367 (66%) and 22,826 (34%) received enoxaparin and UFH, respectively, during their index hospitalization. Demographic, visit-related, clinical, and hospital characteristics differed significantly between groups. Enoxaparin during index hospitalization was associated with 29%, 73%, 30%, and 39% decreases in the adjusted odds of VTE, PE-related mortality, in-hospital mortality, and major bleeding, respectively, compared with UFH (all p < 0.002). Compared with UFH, enoxaparin was associated with significantly lower total hospitalization costs during the index hospitalization and readmission periods. Among adult inpatients with obesity, primary thromboprophylaxis with enoxaparin compared with UFH was associated with significantly lower risks of in-hospital VTE, major bleeding, PE-related mortality, overall in-hospital mortality, and hospitalization costs.

P04 The relationship between air travel and postoperative venous thromboembolism: a systematic review and meta-analysis

Abstract Introduction Surgery is a well-established risk factor for venous thromboembolism (VTE), with fatal pulmonary embolism (PE) remaining the most common preventable death in post-operative patients. Air travel has also been identified as an independent risk factor for VTE, however, there is no guidance on whether air travel in addition to surgery exacerbates this risk. With the increased rates of health tourism, patients increasingly fly to seek surgical intervention. This systematic review and meta-analysis pools published literature to estimate the additional risk of recent air travel after surgery. Methods Articles reporting post-operative VTE incidence in adults with recent air travel were included in our review with data pooled using fixed and random effects. Our primary outcome measured the pooled VTE risk. Results Seven retrospective studies were included with a total of 24975 patients. The odds ratio (OR) of VTE in the flying plus surgery group was 1.96 (95%CI 0.54-7.08). In subgroup analysis of patients with over 4 hours of air travel, odds of VTE were 2.35 (95%CI 0.29-19.36). The incidence of DVT and PE specifically was 0.67% (95%CI 0.31%-1.51%) and 0.41% (95%CI 0%-1.29%) respectively in the flying and surgery group and 0.45% (95%CI 0.10%-2.00%) and 0.55% (95%CI 0.31%-0.86%) in the surgery alone group. Conclusion The meta-analysis demonstrates heterogeneity in studies and a very low certainty of evidence overall considering imprecision and observational study designs. Whilst results did not demonstrate significant increase in VTE risk, further studies should propensity match patients in the cohort to reduce the effect of confounding.

Outcome of pharmacological thromboprophylaxis in hospitalized patients with cirrhosis - a systematic review and meta-analysis.

Portal hypertension in cirrhosis brings about a complex interplay in the risks of bleeding and thrombosis. It is unclear whether hospitalized patients with cirrhosis need pharmacological prophylaxis for venous thromboembolism (VTE), as it may increase the risk of bleeding. We aimed to compare the outcome of hospitalized patients with cirrhosis with and without pharmacological thromboprophylaxis. A comprehensive search of three databases was conducted from inception to August 2022 for studies comparing the outcome of hospitalized patients with cirrhosis with and without pharmacological prophylaxis for VTE. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated for the outcomes of VTE or bleeding. Overall, 12 studies were included in the final analysis. The pooled incidence of VTE in patients with and without thromboprophylaxis was 1.9% (95% CI: 0.8-2.9) and 1.9% (95% CI: 0.9-2.9), respectively. The odds of VTE were comparable between the groups with OR 1.11 (95% CI: 0.76-1.62). The pooled incidence of bleeding events in patients with and without thromboprophylaxis was 6.7% (95% CI: 3.6-9.8) and 10.4% (95% CI: 6.6-14.1), respectively. There was no significant difference in the odds of overall bleeding (OR 0.68; 95% CI: 0.30-1.52) or major bleeding (OR 1.18; 95% CI: 0.55-2.56) between the groups. There was no significant difference in the relative effects on sensitivity analysis. The present analysis could not demonstrate the benefit of pharmacological thromboprophylaxis in reducing in-hospital VTE in patients with cirrhosis. Future studies are required to assess the role of risk prediction models in hospitalized patients with cirrhosis.

Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis.

Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality. Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients. Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels. Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95-1.71, p = 0.10), accounting for 39.14% of the total effect. Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE.

Comment on "Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery".

We read with great interest a recently published work by Raphael et al.1 Their primary hypothesis was to establish independent causality of intraoperative transfusion of red blood cells (RBCs) on venous thromboembolism (VTE) after coronary bypass grafting surgery (n = 751,893) using the database of the Society of Thoracic Surgeons. In their secondary analyses, they further explored the types of VTE, mortality, readmission rate, and length of hospital stay. Their analyses of these data were extensive; however, there are issues that warrant further discussion. First, the overall exposure to RBCs was reported as 17.8% in the current study, but it is important to note the authors handled missing data on intraoperative/postoperative blood products as “no transfusion.” Previous studies in similar patients have shown that intraoperative transfusion rates varied between 12.8% and 60.3% due to variations in institutional practice.2 Missing data labeled as “no transfusion” and omission of any postoperative transfusion before any VTE might have skewed the relationship between intraoperative RBCs and VTE. Second, 37% of women versus 12% of men received blood transfusion. The women were 3 times more likely to receive more than 3–4 units of transfusion than men; however, the adjusted odds ratio for VTE was 0.90 for women. Others also demonstrated that women were more likely to receive >4 U RBC transfusion.3 Women tend to have a lower body mass index (BMI) compared with men, and thus they are more prone to dilutional anemia, and subsequently RBC transfusion. A causality relationship between RBCs and VTE was not supported by the lower odds of VTE in women. As a related issue, we would like to discuss their use of conditional imputation for handling missing data. The extent or presumed pattern of missing data was not specified, but BMI was mentioned as an example of conditional imputation. BMI is known to have a wide variation, particularly by geographic location. Conditional imputation without consideration of regional clustering might have distorted the relationship of BMI (and other predictors) and transfusion in development of the propensity score.4,5 Third, the authors attempted to isolate the effect of intraoperative RBCs by addressing or adjusting all the other risk factors for VTE. From Table 3, the exposures to non-RBC components, recombinant activated factor VII, and factor VIII inhibitor bypassing agent were increased in those with increased RBC transfusion. Hemostatic components were treated as a confounder in the model, but there may be causal associations with both acute and subacute VTE and arterial thromboses.6,7 Patients with severe postoperative bleeding tend to have prolonged hospital stay. The authors showed that cohorts with ≥3 units of RBC had longer hospital stay (mean, 9.8–11.2 days) compared with nontransfused patients (mean, 6.6 days). Although not captured in the database, delayed thromboprophylaxis during a prolonged hospital stay may also exacerbate VTE risk. Lastly, the authors utilized inverse probability treatment weighting method using inverse probability of treatment weighting based on the matching as shown in their Table 2; however, the authors did not mention the handling of extreme weights, which may lead to undue influence of otherwise less common groups (ie, patients with 3 or 4+ units of RBCs) (Tables S1–S10, https://links.lww.com/SLA/E307). While inverse probability treatment weighting adequately accounted for measured confounders pertinent to transfusion (eg, cardiopulmonary bypass [CPB] time), it is speculated that there are residual confounders that impact VTE rates.8 For example, extensive tissue injury and CPB are well known to trigger activations of endothelial cells and leukocytes. Cross-talks between coagulation and immune systems are referred to as “thrombo-inflammation,” and it plays a pivotal role in the pathogenesis of VTE.9 Patient-level inflammation parameters are neither routinely measured nor captured in the database. The statistical adjustment for CPB time does not account for inter-individual variability in inflammation and VTE risk. Given the modest area under the curve statistics they reported for these models, it seems clear there remains an unmet need to improve precision of VTE prediction by including patient-level biomarkers with sufficient sensitivity and specificity. ACKNOWLEDGMENTS A.L.B. conceptualized the letter, and writing up of the first draft of the letter. E.C.W., K.A.T., and K.S. have helped write the letter, and approved the final article. All authors have written and reviewed the article, and approved the final article.