Risk Factors For Venous Thromboembolic Events Research Articles

The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

Risk Factors for Thrombosis in Pregnant People with Sickle Cell Disease: A Multinational Study.

Background People with sickle cell disease (SCD) have exceptionally high rates of maternal morbidity, including increased risk for venous thromboembolic events (VTE). Data from the National Inpatient Sample shows that VTE risk in hospitalized Black pregnant people with SCD is 14 times that of unaffected Black and non-Black pregnant people. 1 There is little disease-specific data to inform anticoagulation (AC) use during pregnancy. 2 The purpose of this study is to describe VTE events in a SCD pregnancy cohort and to identify risk factors for VTE during pregnancy and compare maternal-fetal outcomes for subjects with or without VTE in pregnancy. Methods The Mount Sinai Hospital (MSH) Research Ethics Board and The Johns Hopkins Hospital (JHH) Institutional Review Board approved this retrospective study of pregnant people with SCD of ≥ 20 weeks gestation cared for at MSH, Toronto (1990-2017) or JHH (2000-2021). At MSH and JHH, all pregnant people with SCD and VTE history are prescribed antenatal prophylactic LMWH and for 6-weeks postpartum. At MSH, but not JHH, all receive AC prophylaxis for 6-weeks postpartum. At both centers, hospitalized pregnant people receive prophylactic AC. We stratified subjects by VTE occurrence during pregnancy. First, we described the cohort with VTE during pregnancy, including subject characteristics, VTE recurrence and pregnancy outcomes. Second, we compared cases with a first pregnancy with VTE to controls without VTE. We excluded repeat pregnancies in both groups. We compared cases and controls by SCD characteristics, medication use before pregnancy, and pregnancy outcomes. Painful events were defined as pain requiring acute care or hospital admission. Chronic transfusion therapy (CTT) was defined as pregnancies treated with scheduled, prophylactic transfusion; opioid use was defined as receiving an outpatient opioid prescription during pregnancy. We used the Chi-squared test for categorical variables and Wilcoxon signed-rank tests for continuous variables. A p-value of <0.05 was considered significant. Results There were 290 singleton pregnancies in 199 subjects. Half of the pregnancies were first pregnancies (142/290), with fewer second (51/290), third (2/290), fourth (3/290) or fifth (1/290) pregnancies. The cohort comprised of 58% subjects with HbSS/HbSβ 0, while 42% had HbSC/HbSβ+ genotype (Table 1). VTE occurred in 7% of pregnancies (20/290) including deep vein thrombosis (DVT, N=9), pulmonary embolism (PE, N=8), DVT+PE (N=3). Median age was 27 years (IQR 23,30). Before pregnancy, most VTE subjects received hydroxyurea (N=10). During pregnancy, six received CTT. Fourteen subjects had VTE in a single pregnancy; three had VTE recurrence in subsequent pregnancies. All three had HbSS/HbSβ 0. Two subjects had VTE history outside of pregnancy. One had DVT in two consecutive pregnancies and was prescribed AC in both pregnancies due to history of VTE. VTE occurred in first (N=4), second (N=8), third (N=4), fourth (N=1) and fifth (N=4) pregnancies. Most VTE occurred at JHH (11 JHH vs 6 MSH, p=0.008). To investigate SCD-specific risk factors for VTE in pregnancy, we compared characteristics in VTE subjects (N=17) to no-VTE subjects (N=182) by first study pregnancy with an event or first study pregnancy while enrolled in the study. VTE was associated with markers of disease severity including history of VTE before pregnancy (6/17 VTE vs 8/182 no-VTE, p<0.001), ACS during pregnancy (7/17 VTE vs 19/182 no-VTE, p<0.001), painful events requiring acute care during pregnancy (16/17 VTE vs 119/182 no-VTE, p=0.015) and hydroxyurea use before pregnancy (10/17 VTE vs 35/184 no-VTE, p<0.001). There was no difference in age or genotype. VTE was associated with earlier delivery and c-section delivery (Table 1). Conclusion In this study, 7% of cohort pregnancies had VTE. This rate exceeds reports from administrative datasets. 1 This may be due to the acuity of patients cared for at our centers and/or reflect undercounting of VTE in administrative datasets. In pregnant people with SCD, VTE is associated with VTE history, intrapartum painful events and ACS. Interventions to reduce acute events in pregnancy may help reduce VTE risk. While AC can be beneficial in preventing thrombotic events, careful assessment is essential to manage bleeding risks. Prospective data is needed to define the subpopulation of pregnant SCD patients who would benefit from AC prophylaxis antenatally.

Venous Thromboembolism in Adolescents and Young Adults with Acute Lymphoblastic Leukemia Treated on a Pediatric-Inspired Regimen

Introduction Adolescent and young adult (AYA) patients (pts) with acute lymphoblastic leukemia (ALL) can be effectively treated with pediatric-inspired ALL regimens which incorporate asparaginase (ASP). Asparaginase is associated with increased venous thromboembolic (VTE) complications. We examined the incidence of and risk factors for VTE events as well as the impact of VTE events on outcomes of AYA pts treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols. Methods We identified pts aged 15-50 years diagnosed with Philadelphia chromosome negative (Ph-neg) ALL treated on 4 multicenter DFCI Consortium protocols (Pediatric 00-001, Pediatric 05-001, Adult 01-175, and Adult 06-254), or treated as per these protocols between 2000-2021. All regimens included an ASP containing induction, 30 weeks of continuous ASP exposure during consolidation and a continuation phase without ASP. The use of a pegylated vs non-pegylated ASP formulation varied between protocols. As ASP exposure is associated with both VTE and survival, it may confound the association between VTE and survival; thus, to ameliorate confounding, all survival associated outcomes were conducted on pts who remained on protocol for at least 1 year (encompassing ASP exposure). Overall survival (OS) and event free survival (EFS) were presented with Kaplan Meier curves and comparisons were made by the log-rank test. Cumulative incidence of VTE, relapse (CIR) and non-relapse mortality (NRM) were estimated by the cumulative incidence method with the appropriate competing risks, and comparisons were made by the Gray test. Cox regression analysis was fit to evaluate the effect of covariates on OS and EFS. Results Among 341 Ph-neg AYA ALL pts aged 15-50 years, 109 (32%) experienced one or more VTE events. The baseline characteristics did not differ between pts who experienced a VTE and those who did not experience a VTE, except for a higher rate of VTE among overweight/obese pts (BMI≥25 kg/m 2, n=56, 38%) vs normal BMI (n=53, 27%, p=0.04) and a lower rate of VTE in patients with hyperdiploid vs non-hyperdiploid karyotype (n=4, 12% vs n=105, 34%, p<0.01). Of the 109 pts with VTE, 9 (8%) experienced sinus vein thrombosis (2.6% in the overall cohort) and 19 (17%) experienced at least one additional VTE. Most initial VTE events occurred during consolidation (n=78, 72%), followed by induction (n=22, 20%), and continuation/follow-up (n=9, 8%). The 2-yr cumulative incidence of VTE was 32% (95% CI, 27%-37%) and was similar between patients who were treated with non-pegylated ASP vs. pegylated ASP (n=43, 30% vs n=65, 35%, p=0.35). The 2-yr cumulative incidence of VTE was higher in the BMI ≥ 25 kg/m 2 group compared to those with normal BMI (38% vs 28%, p=0.035, Figure 1) and was the only covariate associated with increased VTE risk in the univariate regression model (HR 1.49, 95% CI, 1.03-2.17). Among pts who completed ≥ 1 year of protocol therapy (n=220), the 4-year OS was 92%, and did not differ between pts who experienced VTE vs. not (94% vs 90%, p=0.99, Figure 2). Similarly, there were no differences in 4-year CIR (14% vs 11%, p=0.50), NRM (0% vs 3%, p=0.37), and EFS (86% vs 86%, p=0.79). In univariate analysis for OS, obese BMI (>30 kg/m 2), higher WBC, B-cell immunophenotype, and fewer weeks on ASP therapy were associated with worse OS; all remained predictive in the multivariable model. In the uni- and multivariable analysis for EFS, higher WBC and B-cell immunophenotype were associated with worse EFS. Notably, VTE was not associated with worse OS or EFS in all regression analyses. Conclusion Among AYAs treated on DFCI ALL Consortium protocols, VTE events were frequent, occurred mostly during consolidation phase and were more common among pts with overweight/obese BMI vs normal BMI. Sinus vein thrombosis was rare. VTE incidence did not impact CIR, NRM, EFS or OS, suggesting that VTE is a manageable toxicity.

Patient-Specific Venous Thromboembolic Event Prophylaxis in Total Joint Arthroplasty - Literature-Supported Guidelines.

Following total joint arthroplasty (TJA), venous thromboembolic events (VTE) are a known complication that may result in increased hospitalization cost as well as morbidity. Numerous investigations have documented patient-specific factors that place an individual at increased risk of VTE after TJA. Potential risk factors for VTE include genetic predisposition, history of a prior VTE event, revision surgery and patient comorbidity factors. The American Academy of Orthopedic Surgeons and The American College of Chest Physicians have both provided recommendations for VTE prophylaxis after orthopedic surgery. However, among orthopedic surgeons, there remains a lack of consensus regarding the appropriate agent and time course for prophylactic anticoagulation after TJA. In this study, we review the evidence-supported patient-specific factors that confer an increased risk of VTE in the TJA postoperative period. Furthermore, we describe the VTE prophylaxis regimen used at our home institution after TJA for low- and high-risk patients as well as a recommendation for cessation or continuation of anticoagulation regimens that patients were on preoperatively for comorbid conditions.

Assessment of Postoperative Venous Thromboembolic Complications

BACKGROUND: Postoperative venous thromboembolic events (VTEs) are a preventable cause of death. Adherence to available guidelines and prophylactic measures is suboptimal. This study examined postoperative VTEs prevalence, prophylaxis guideline adherence, and VTEs risk factors among surgical patients at King Abdulaziz University Hospital in Saudi Arabia. METHODOLOGY: This retrospective study analyzed VTEs patients from August 2020 to November 2022. Medical records collected data on patients, procedures, prevention, guideline adherence, and VTEs diagnosis. The statistical analysis evaluated the link between prophylactic measures and VTEs occurrence. RESULTS: Thirty-one (32%) of the 97 VTEs diagnosed in patients were postoperative VTEs. Mortality rates were 18.5%, and for postoperative VTEs patients were 12.9%. Most patients (87.1%) were at high risk (Caprini score ≥ 5) for VTEs. Abdominopelvic procedures were 64.5% of cases. Approximately 60% of patients received postoperative prophylaxis. Enoxaparin was the most frequently used prophylaxis method (63.1%). Mechanical prophylaxis was used in 36.8% of patients who received prophylaxis. Compliance for extended prophylaxis was only 10.5%. Late initiation of prophylactic measures was significantly associated with deep vein thrombosis occurrence. CONCLUSION: The study emphasizes the need to follow prophylaxis guidelines. Improving compliance with prophylactic measures, especially for high-risk patients, can potentially reduce postoperative VTEs.

Risk Factors for Venous Thromboembolic Events in Children With Acute Musculoskeletal Infections.

Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs. A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors. Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8d, P <0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5d, P =0.001), and longer time to fever resolution (median 25.7 vs. 162h, P =0.004). VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.

Risk and timing of venous thromboembolism in patients with gastrointestinal cancer: a nationwide Danish cohort study

AimsCancer is a well-known risk factor of venous thromboembolism (VTE). Some cancers are believed to be more thrombogenic. The purpose of this study was to investigate the characteristics of patients...

Risk factors of venous thromboembolism after incisional ventral hernia repair.

The problem of venous thromboembolic events (VTE) after incisional hernia repair remains relevant. According to the literature the frequency of VTE ranges from 0.2 to 4.2%. The data on risk factors of VTE in this cohort of patients are scarce. Aim of our study is to find frequency and risk factors for VTE development in patients who underwent surgery for incisional ventral hernia. There were 240 patients enrolled in our retrospective study. We included patients, who were operated for incisional hernia in Saveljev University Surgery Clinic from January 2018 to December 2019. Compression duplex ultrasound of lower extremity veins was performed within median 3days (min 1day, max 7days) after surgery for all participants. The primary endpoint was the occurrence of the VTE event, including deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE was detected in 19 patients, which accounted for 7.9% in analyzed cohort. All patients received standard pharmacological prophylaxis. There were 3 (1.3%) proximal, 16 (6.7%) distal DVT, in one patient (0.4%) distal thrombosis was complicated by symptomatic pulmonary embolism. In multivariate Cox proportional hazard model was found that component separation (HR 3.99, 95% CI 1.14-14.0, p = 0.03), duration of operation in hours (HR 1.67. 95% CI 1.13-2.5, p = 0.011) and body mass index (HR 1.13, 95% CI 1.02-1.2, p = 0.02) were statistically significant risk factors. The incidence of postoperative VTE in patients after incisional hernia repair is high with a predominant distal DVT as a thrombotic event. Component separation, duration of operation and body mass index are statistically significant factors of VTE in patients undergoing surgery for incisional hernia.

Cell Product Differences on Incidence of Venous Thromboembolism in Patients Treated with CAR T-Cells for Aggressive B-Cell Lymphomas

Introduction Chimeric antigen receptor T (CAR T)-cell therapy has substantial activity in relapsed lymphoid malignancies. However, it is associated with important complications, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolic events (VTEs) following CAR T-cells have been reported with variable incidence. Risk factors for the development of VTEs following CAR T-cell therapy are largely unknown, including whether the CAR T-cell construct is associated with increased VTEs. Methods We retrospectively evaluated patients treated at our institution who received CAR T-cell therapy for non-Hodgkin lymphoma between May 2018 and January 2022. Baseline characteristics and outcomes were collected. VTEs included deep venous thrombosis and pulmonary embolism. The cumulative incidence (CI) of VTE was calculated with death as competing risk and comparisons between groups were done with Gray test. Univariate comparisons of baseline parameters were performed with Fisher's exact test evaluating the following covariates: age (older or younger than 70 years), LDH and C-reactive protein levels, ECOG performance status, revised IPI, BMI, personal history of VTE, and stage. Due to the low number of VTEs, we did not attempt multivariate modeling based on baseline characteristics. All analyses were performed using R. This study was approved by our Institutional Review Board. Results We identified 95 patients treated with CAR T-cells between May 2018 and January 2022. The majority had diffuse large B-cell lymphoma (DLBCL) (88, 93%). Baseline characteristics are listed in Table 1. Prior history of VTE occurred in 16 patients and 27 received at least one dose of therapeutic or prophylactic anticoagulation post-CAR T infusion prior to developing VTE. Most patients had central venous access during their hospitalization for CAR T cell therapy (n = 91). A total of 56 patients received axicabtagene ciloleucel (58.9%), 30 patients received tisagenlecleucel (31.6%), 5 patients received brexucabtagene autoleucel (5.3%), and 4 received lisocabtagene maraleucel (4.2%). Post-CAR T VTE occurred in 13 patients (14%); median time to VTE (IQR) was 15 days (7-48), with a 100-day cumulative incidence of 12%. All VTEs were DVTs and the majority were PICC line-associated (10, 77%). The incidence of VTE was higher for patients treated with axicabtagene ciloleucel or brexucabtagene autoleucel in contrast to 41BB-containing constructs (16% vs. 3%, p = 0.03) (Figure 1). Among baseline characteristics, a prior history of VTE was associated with increased risk of subsequent VTE (39% vs. 13% without prior VTE, p = 0.04). The 100-day CI of VTE for patients with and without CRS were 15% and 4% (p = 0.09), while the 100-day CI of patients with and without ICANS were 18% and 7% (p = 0.09). Subgroup analysis of patients treated with CD3ζ/CD28 signaling showed that 100-day VTE CI was higher among patients with a prior history of VTE (33% vs. 12%, p = 0.03) and those with BMI of ≥ 30 (38% vs. 11%, p = 0.03). We did not observe an increased incidence of VTE in patients with baseline ECOG performance status ≥ 2, stage III/IV disease, elevated baseline lactate dehydrogenase or C-reactive protein. After a median follow up of 24 months (IQR 13-36), the median progression free survival (PFS) was 7 months (95% CI = 4-12) while the median overall survival (OS) was 14 months (95% CI = 11-19), there were no statistically significant differences in PFS or OS among patients with and without VTE. Conclusions VTEs are an emerging toxicity associated with CAR T cell therapy. We show that increased VTE incidence at 100 days is associated with the use of CD3ζ/CD28 CAR T-cells. This difference may correlate with differing degrees of systemic inflammatory response, as previous reports have detailed higher incidence of high-grade CRS with axicabtagene ciloleucel vs. tisagenlecleucel, and other construct-specific factors may further increase VTE risk in patients with established VTE risk factors (e.g. history of VTE and obesity). We also observed that a large proportion of post CAR T VTEs corresponded to line-associated DVTs. Taken together, these findings may help identify patients at increased risk of VTE after CAR T-cell therapy and potentially guide decisions on surveillance, choice of central access, or prophylactic anticoagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Chemoprophylactic Anticoagulation Following Lumbar Surgery Significantly Reduces Thromboembolic Events After Instrumented Fusions, Not Decompressions.

Retrospective cohort. To quantify any reduction in venous thromboembolic events (VTEs) caused by chemoprophylaxis among lumbar surgery patients. Chemoprophylactic anticoagulation (chemoprophylaxis) is used to prevent VTE after lumbar surgery. However, the treatment effect of chemoprophylaxis has not been reported among spine surgery patients, as conventional statistical methods preclude such inferences. A total of 1243 consecutive lumbar fusions and 1433 noninstrumented lumbar decompressions performed at our institution over a six-year period were identified, and clinical and demographic data were collected, including on VTE events within 30 days postoperatively. Instrumented lumbar fusions and noninstrumented lumbar surgeries were analyzed separately. Patients who were given chemoprophylaxis (treatment) and controls were matched according to known VTE risk factors, including age, body mass index, sex, diabetes, chronic kidney disease, history of VTE, estimated blood loss, length of surgery, transfusion, whether surgery was staged, and whether surgery used an anterior approach. K-nearest neighbor propensity score matching was performed, and the treatment effect of chemoprophylaxis was calculated. Unadjusted, there was no difference in the rate of VTE between treatment and controls in either population. Baseline clinical and demographic characteristics differed significantly between treatment and control groups. In all, 575 lumbar fusion patients and 435 noninstrumented lumbar decompression patients were successfully propensity score matched, yielding balanced models (Rubin B <25, 0.5<Rubin R <2.0) and >60% reduction in known bias for both populations. The treatment effect of chemoprophylaxis after lumbar fusion in our patient population was a reduction in VTE incidence from 9.4% to 4.2% ( P <0.05), and propensity score adjusted regression confirmed a reduced odds of VTE with chemoprophylaxis (odds ratio=0.37, P =0.035). The treatment effect was not significant for noninstrumented lumbar decompression patients. Among patients undergoing instrumented lumbar fusions, chemoprophylactic anticoagulation causes a significant reduction in VTE, but causes no significant reduction among patients undergoing noninstrumented lumbar decompression.

1590P Interest of preventive treatment with anticoagulant in older patients with cancer on venous thrombo-embolic events (ANTIGONE study): Design and baseline results

Venous thromboembolic events (VTE) are frequent during cancer and increase with age. Their preventions by anticoagulants in older patients with cancer has not been established and very few data exist in older frail subjects. The primary Objective: To compare the risk of VTE in older patients with cancer treated or not treated with preventive anticoagulant therapy. The secondary objectives are to assess the bleeding risk in both groups and to identify risk factors of VTE.

Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy.

An unsafe hematocrit threshold for men receiving testosterone therapy (TT) has never been tested. This study seeks to determine whether secondary polycythemia among men receiving TT confers an increased risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE). Using a multi-institutional database of 74 million patients, we identified 2 cohorts of men with low testosterone (total testosterone <350 ng/dl) who received TT and subsequently either developed polycythemia (5,887) or did not (4,2784). Polycythemia was defined as hematocrit ≥52%. As a secondary objective, we identified 2 cohorts of hypogonadal men without polycythemia, who either did (26,880) or did not (27,430) receive TT. Our primary outcome was the incidence of MACE and VTE in the first year after starting TT. We conducted a Kaplan-Meier survival analysis to assess differences in MACE and VTE survival time, and measured associations following propensity score matching. A total of 5,842 men who received TT and developed polycythemia were matched and compared to 5,842 men who did not develop polycythemia. Men with polycythemia had a higher risk of MACE/VTE (number of outcomes: 301, 5.15%) than men who had normal hematocrit (226, 3.87%) while on TT (OR 1.35, 95% CI 1.13-1.61, p <0.001). In hypogonadal men who received testosterone, no increased risk of MACE and VTE was identified as compared to hypogonadal men naïve to TT. Developing polycythemia while on TT is an independent risk factor for MACE and VTE in the first year of therapy. Future research on the safety of TT should include hematocrit as an independent variable.

ABCL-230: Prevalence, Patterns, and Predictors of Venous Thromboembolic Events in Patients Undergoing Salvage Chemotherapy and Autologous Stem Cell Transplant for Relapsed Lymphomas

The majority of relapsed or refractory lymphoma patients undergo salvage chemotherapy and autologous stem cell transplant (ASCT). Data on venous thromboembolic events (VTEs) in this setting are scarce. This study aims to evaluate the incidence, pattern, and risk factors for VTEs in this group of patients across the continuum of their care. The medical records of adult patients, aged ≥ 18 years, who were diagnosed and treated at our institution from 2007 to 2017 with refractory or relapsed lymphoma and received salvage therapy followed by high-dose chemotherapy and autologous stem cell transplant were retrospectively reviewed. A total of 216 patients, with a median age of 31 (range: 19–60) years, were identified. In total, 36 (16.7%) patients had VTE, mostly in the upper extremity (n=28, 77.8%); 50.0% were related to central venous catheter. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) (29.2% <i>vs</i> 5.9%, p< 0.001), mediastinal involvement (25.9% <i>vs</i> 11.5%, p=0.025) and in patients with longer hospital stay (22.1% <i>vs</i> 9.5%, p=0.036). In multivariate analysis, high LDH (OR: 7.66; 95% CI: 2.79–21.04, p<0.001) and mediastinal involvement (OR, 3.64; 95% CI: 1.53–8.70, p=0.002) were associated with significantly higher rates of VTE. In conclusion, patients with relapsed lymphoma undergoing ASCT are at higher risk for VTE, especially those with high LDH and mediastinal involvement. Thromboprophylaxis might be considered in these settings.

Venous Thromboembolism Among Patients With Inflammatory Bowel Diseases is Not Related to Increased Thrombophilia: A Case-Control Study.

The aim was to assess whether thrombophilia significantly contributes to the risk of venous thromboembolic events (VTEs) in patients with inflammatory bowel disease (IBD). Patients with IBD have a high risk of VTE. The underlying mechanism has been only partially defined. A case-control study in adults with IBD and an episode of VTE (IBD-VTE) were matched and compared with non-IBD patients with a VTE (non-IBD-VTE). The study population was comprised of patients seen in 2 tertiary medical centers in Israel between 2000 and 2013. Characteristics of IBD and risk factors for VTE were retrieved from medical charts, and a comprehensive thrombophilia panel was completed in all patients. Forty-four IBD-VTE cases (27 Crohn's disease) were matched with 127 non-IBD-VTE controls. The majority of VTE had a clear etiology and were considered provoked events. Provoked and unprovoked VTE rates were not different between the 2 groups. Likewise, thrombophilia rates were similar among patients with IBD-VTE and controls (40.9% vs. 53.5%, respectively, P=0.14). However, among patients with unprovoked VTE, thrombophilia rates were significantly lower in the IBD-VTE group compared with controls (42.1% vs. 70.7%, respectively, P=0.03). Among patients with IBD-VTE, an unprovoked event, and negative thrombophilia, 77% had active inflammation at the time of VTE. Thrombophilia rates are similar among patients with IBD-VTE and controls but are less common among patients with unprovoked IBD-VTE. This finding suggests that either inflammation or other novel pathways drive VTE in patients with IBD.

Obesity and Mortality Among Patients Diagnosed With COVID-19

LettersJune 2021Obesity and Mortality Among Patients Diagnosed With COVID-19FREEAnastasios Kollias, MD, PhD, Konstantinos G. Kyriakoulis, MD, Konstantinos Syrigos, MD, PhDAnastasios Kollias, MD, PhDNational and Kapodistrian University of Athens and Sotiria Hospital, Athens, GreeceSearch for more papers by this author, Konstantinos G. Kyriakoulis, MDNational and Kapodistrian University of Athens and Sotiria Hospital, Athens, GreeceSearch for more papers by this author, Konstantinos Syrigos, MD, PhDNational and Kapodistrian University of Athens and Sotiria Hospital, Athens, GreeceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0063 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: We read with interest Tartof and colleagues' study (1) showing that body mass index (BMI) independently predicted mortality in 6916 patients with COVID-19. High BMI was also shown to be more strongly associated with COVID-19 mortality in younger adults and men.Emerging evidence suggests that SARS-CoV-2 may induce an excessive immune response leading to cytokine storm and coagulation disorders (2). Thus, severe COVID-19 is associated with an increased risk for venous thromboembolic events (VTEs) (2). The latter risk seems to be determined by 3 factors: patient characteristics, including well-established risk factors for VTE; quarantine-associated inactivity, hospitalization conditions, and antithrombotic interventions; and SARS-CoV-2–specific factors (2). In terms of patient characteristics, BMI represents a well-established risk factor for VTE. A recent systematic review and dose–response meta-analysis of cohort studies among 4 million participants showed a significant linear relationship between BMI and risk for VTE (3). The increased risk for VTE among patients with COVID-19 and the preliminary evidence suggesting a survival benefit with the use of antithrombotic treatment have been recognized by international societies that strongly recommend the use of thromboprophylaxis in all hospitalized patients (4).It would be interesting if studies reporting on mortality in patients with COVID-19 made available BMI-related data on VTE incidence and the thromboprophylaxis protocols used. Obesity is known to be associated with an increased risk for a proinflammatory and prothrombotic state, which can also be aggravated by SARS-CoV-2 (1). It could be argued that obese patients have a higher risk for VTE that in turn could partly account for their higher incidence of adverse outcomes in COVID-19. Furthermore, recent autopsy studies have recognized a high incidence of deep venous thrombosis in patients with COVID-19, with pulmonary embolism being identified as a direct cause of death (5). Physicians dealing with patients with COVID-19 should be aware of the high risk for VTE and the need for thromboprophylaxis, especially when obesity is present.

A Risk-benefit Analysis of Prophylactic Anticoagulation for Patients with Metastatic Germ Cell Tumours Undergoing First-line Chemotherapy

BackgroundIt remains unclear which patients with metastatic germ cell tumours (mGCTs) need prophylactic anticoagulation to prevent venous thromboembolic events (VTEs). ObjectiveTo assess the risk and onset of VTEs stratified by risk factors. Design, setting, and participantsThis multi-institutional retrospective dataset included mGCT patients treated with first-line platinum-based chemotherapy. InterventionPatients with prophylactic anticoagulation were excluded. Outcome measurements and statistical analysisA regression analysis was performed to select risk factors for VTEs. The simulated number needed to treat (NNT) and the number needed to harm (NNH) with prophylactic anticoagulation were calculated based on the cumulative incidences retrieved from this study and hazard rates of recently published trials describing the efficacy of prophylactic anticoagulation to prevent VTEs and the risk of bleeding events. Results and limitationsFrom 1120 patients, 121 (11%) had a VTE, which occurred prior to chemotherapy in 49 (4%) and on or after chemotherapy in 72 (6%). Six patients (<1%) had a bleeding event without anticoagulation. After backward regression, the one risk factor for a VTE during or after chemotherapy was the use of a venous access device. The simulated cumulative VTE incidence from prophylactic anticoagulation for patients on or after chemotherapy would translate into an NNT of 45 (95% confidence interval [CI] 36–56) and an NNH of 186 (95% CI 87–506). Limitations are mainly related to the retrospective nature of the study. ConclusionsThe mGCTs associated VTEs are most common before and during, but not after, chemotherapy. Avoiding venous access device and/or prophylactic anticoagulation with an acceptable risk-benefit profile may decrease VTE occurring on chemotherapy. Patient summaryWe found that venous thromboembolic events (VTEs) occur rarely after chemotherapy. Based on experience of prophylactic anticoagulation in other cancers, we conclude that the risk of VTE in men undergoing chemotherapy for metastatic germ cell tumours can be decreased by thromboprophylaxis with a reasonable risk-benefit profile and by avoidance of venous access devices.

Heterogeneity in reporting venous thromboembolic phenotypes in COVID-19: methodological issues and clinical implications.

SummaryCOVID‐19 is associated with increased risk of venous thromboembolic events (VTE). However, there is significant heterogeneity in the thromboembolic phenotypes of COVID‐19 patients (deep vein thrombosis, pulmonary embolism/thrombosis). The latter might be partly attributed to the variation in VTE risk factors in COVID‐19 patients including: (i) patients’ characteristics; (ii) hospitalization conditions and interventions; and (iii) SARS‐CoV‐2‐specific factors (coagulopathy, endothelial injury/microthrombosis). Furthermore, there is methodological heterogeneity in relation to the assessment of VTE (indications for screening, diagnostic methodology, etc). Physicians should be aware of the increased VTE risk, strongly consider VTE screening, and use thromboprophylaxis in all hospitalized patients.

Inherited Risk Factors of Thromboembolic Events in Patients with Primary Nephrotic Syndrome.

Background and objectives. Venous thromboembolic events (VTEs) are among the most important complications of nephrotic syndrome (NS). We conducted a study that aimed to determine the prevalence of inherited risk factors for VTE in NS and to identify which factors are independent predictors of VTE. Materials and Methods. Thirty-six consecutive patients with primary NS that underwent percutaneous kidney biopsy between January 2017 and December 2017 were enrolled in this retrospective, observational study. VTEs were the primary outcome. Baseline demographic and biochemical data were collected from medical records, and genetic testing was done for polymorphisms of Factor V, PAI, MTHFR, and prothrombin genes. Results. The incidence of VTE was 28%, and the median time to event was 3 months (IQR: 2–9). The prevalence of inherited risk factors was 14% for Factor V Leiden mutation, 5.6% for prothrombin G20210A, 44.5% for PAI, and 27.8% for each of the two polymorphisms of the MTHFR gene. On multivariate analysis, the presence of at least two mutations was independently associated with the risk of VTE (HR, 8.92; 95% confidence interval, CI: 1.001 to 79.58, p = 0,05). Conclusions. These findings suggest that genetic testing for inherited thrombophilia in NS could play an important role in detecting high-risk patients that warrant prophylactic anticoagulation.

Aggressive lymphoma subtype is a risk factor for venous thrombosis. Development of lymphoma - specific venous thrombosis prediction models.

Venous thromboembolic events (VTE) are a frequent complication of lymphoma. We conducted a retrospective analysis to compare VTE risk in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Subjects were randomly assigned to training and validation sets to identify risk factors of VTE and evaluate risk model performance, including the Khorana score. A group of 790 patients were diagnosed from 2002 to 2014 (DLBCL = 542, FL = 248). Median follow- up was 49 months. We observed 106 VTE, with higher incidence in DLBCL (5-year cumulative incidence = 16.3% vs 3.8% in FL patients). Five-year OS for patients with VTE was 51.4% vs 73.1% in patients without VTE (P < .001). Baseline VTE risk factors identified in the training cohort included lymphoma subtype, previous VTE, ECOG performance status ≥2, decreased albumin, increased calcium, elevated WBC, absolute lymphocyte count or monocyte count, and presence of bulky disease. Addition of new variables to the Khorana score improved its performance measured by Akaike information criterion and Concordance index. A new risk model including lymphoma subtype, albumin, WBC count, and bulky disease was validated in time-based ROC analyses. These findings were confirmed in the validation cohort. Lymphoma subtypes have different VTE risk. The effect of lymphoma subtype was independent from disease burden and the use of systemic therapy. The Khorana risk-score was validated in time to event analyses, and a more robust lymphoma-specific VTE risk score is proposed. These findings suggest lymphoma patients with highest VTE risk can be identified with baseline parameters.