Clinical Venous Thromboembolism Research Articles

Randomised comparative effectiveness trial of Pulmonary Embolism Prevention after hiP and kneE Replacement (PEPPER): the PEPPER trial protocol

IntroductionMore than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%–0.5% fatal PE, and over 1000...

Prevalence, Patterns, and Predictors of Venous Thromboembolic Events in Patients Undergoing Salvage Chemotherapy and Autologous Stem Cell Transplantation for Relapsed Lymphomas.

Almost 25% of patients with lymphoma may have relapse or develop refractory disease, and a majority of such patients undergo salvage chemotherapy and autologous stem cell transplantation (ASCT). Data on venous thromboembolism (VTE) in this setting are scarce. This study aimed to investigate the prevalence and factors that may increase the risk of VTE in such patients. Adult patients who were diagnosed with lymphoma and received salvage chemotherapy and ASCT were included in the study, and the subgroup with radiologically confirmed VTE were identified. Correlations between different clinical and laboratory variables and VTE were evaluated. A total of 216 patients (median age, 31 [range, 19-60] years) were enrolled in the study. Most patients (n = 140, 64.8%) had Hodgkin's lymphoma, while 54 (25.0%) had diffuse large B-cell lymphoma. A total of 36 (16.7%) patients had VTE, mostly as upper extremity deep vein thrombosis (n = 28, 77.8%); 18 (50%) of the cases were related to central venous catheter insertion. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) level (29.2% vs. 5.9%, p < 0.001), those with mediastinal involvement (25.9% vs. 11.5%, p = 0.025). and those with longer hospital stay (22.3% vs.9.5%, p = 0.036). In the multivariate analysis, high LDH level (odds ratio (OR), 6.53; p < 0.001), mediastinal involvement (OR, 2.70; p = 0.005) and hospital stay ≥24 days (OR, 2.71; p = 0.007) were all associated with significantly higher VTE rates. Patients with relapsed lymphoma undergoing salvage chemotherapy and ASCT are at higher risk for VTE, especially in those with high LDH level, mediastinal involvement, and prolonged hospital stay. If no contraindications exist, thromboprophylaxis might be considered in these settings.

Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown.Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation.Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis.Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02).Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Real World Validation of VTE Risk Models in Newly Diagnosed Multiple Myeloma in a Community Setting

Background:Multiple Myeloma (MM) is associated with increased risk for venous thromboembolism (VTE). Treatment, such as dexamethasone, immunomodulatory drugs (IMID), alkylating agents, and doxorubicin, alter hemostatic pathways and thus promote thrombogenesis 1. MM patients with VTE have a 3-fold increase in mortality compared to those without VTE, so identifying those at risk and aiming to prevent VTE events is important 2. Several clinical VTE risk prediction scores have been developed, including the SAVED score, IMPEDE VTE score, and more recently the PRISM score 2,4,5. The National Comprehensive Cancer Network suggests that patient with MM on IMID therapy should be on aspirin, or therapeutic anticoagulation for those at “high risk”3. However, it remains unclear which risk model, if any, should be used.Our objective was to validate the three published risk assessment tools in a community setting and assess the predictive ability of each.Methods:We conducted a retrospective chart review of all patients with newly diagnosed multiple myeloma who started chemotherapy at Gundersen Health System (La Crosse, WI) between 2010 and 2020 who had at least 6 months of follow up documented. Patients with prior indication for ongoing therapeutic anticoagulation or a diagnosis of VTE within 6 months prior to starting therapy were excluded. Total scores for IMPEDE VTE, SAVED and PRISM scores were calculated from the chemotherapy start date. Statistical analysis included Chi-square, Fisher's exact and Wilcoxon rank sum tests, and Kaplan Meier survival analysis. A p-value ≤ 0.05 was considered significant and all analysis was completed in SAS version 9.4.Results:Our cohort contained 123 patients diagnosed with MM. Average age was 68 years (SD 12.1, range 37-92). Our study included 68 (55%) males and 55 (45%) females with 121 (98%) being White/Caucasian. The mean BMI of patients was 29.4 kg/m2 (SD 7.0, range 18.6-54.4). Kaplan Meier survival analysis showed a 5-year survival rate of 53.1% (95% CI [42.7%, 63.4%]). In the entire cohort, 10 (8.1%) patients were diagnosed with VTE (as compared to 5.8% in IMPEDE study, 8.7% in SAVED study and 8.2% in PRISM study) with 80.0% occurring within 6 months of treatment start date. Aspirin was the most frequently used agent for thromboprophylaxis with 88 (86.3%) patients receiving either 81, 162, or 325 mg of aspirin. IMID therapy was given to 76 (61.8%) patients, 114 (92.7%) received dexamethasone and 114 (92.7%) received proteasome inhibitors. Amongst those on IMIDs, 72 (94.7%) patients received prophylaxis, most commonly aspirin. Abnormal metaphase cytogenetics were noted in 104 (85.4%) patients.Neither the IMPEDE VTE (p=0.6), SAVED (p=0.9) nor PRISM risk scores (p=0.3) were able to statistically predict VTE outcome in our patient population. Using the IMPEDE score, 7 patients in the intermediate risk group and 3 patients in the low-risk group had a VTE. In the SAVED model, 5 patients in the low-risk group and 5 patients in the high-risk group had a VTE. Using the PRISM risk score, all 10 of the patients with VTE were in the intermediate risk group. Most patients who were on IMID therapy fell into the intermediate risk group on the IMPEDE VTE and PRISM scoring systems, and the SAVED score had an approximately equal patient distribution between the high risk and low risk group.Conclusions:Our patients with multiple myeloma had similar rates of VTE as compared to the published models, with the majority occurring in the first 6 months of chemotherapy. In total, our patients on IMID therapy received appropriate prophylaxis with aspirin. Overall, 8.1% of our patients had a VTE event. However, none of the three risk models were able to predict the development of VTE. In fact, many of the VTE events occurred in patients who were felt to be low or intermediate risk. While the sample size is small and from a single health system, we had excellent follow up and ability to closely examine each chart for treatment and outcomes. Further efforts should focus on collaboration across institutions to increase the sample size, to validate and compare existing models. The majority of myeloma treatment occurs in the community; thus, it is important to ensure the findings are reproducible in that patient population. DisclosuresNo relevant conflicts of interest to declare.

Predictors of venous thromboembolism among infants in children's hospitals in the United States: a retrospective Pediatric Health Information Study.

ObjectivesExamine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants <6 months discharged from U.S. NICUs; (2) Associations between sociodemographic and clinical factors and VTE; (3) Secondary outcomes related to VTE.Study designMultivariable logistic regressions examined associations between VTE and sociodemographic and clinical factors among infants <6 months discharged from Pediatric Health Information System (PHIS) NICUs between 2016 and 2019.ResultsOf 201,033 infants, 2720 (1.35%) had diagnosed VTE. Birthweight 300–1000 g (aOR 3.14, 95% CI 2.54–3.88), 1000–1500 g (aOR 1.77, 95% CI 1.40–2.42) versus 2500–3999 g, and public (aOR 1.18, 95% CI 1.02–1.37) versus private insurance were associated with increased odds of VTE, as were CVC, TPN, mechanical ventilation, infection, ECMO, and surgery. All types of central lines (non-tunneled and tunneled CVCs, PICCs, and umbilical catheters) had higher odds of VTE than not having that type of line. CVCs in upper versus lower extremities had higher odds of VTE.ConclusionInfants with risk factors may require monitoring for VTE. Results may inform VTE prevention.

Age, personal and family history are independently associated with venous thromboembolism following acute Achilles tendon rupture

PurposeThe primary aim was to determine independent patient, injury and management-related factors associated with symptomatic venous thromboembolism (VTE) following acute Achilles tendon rupture (ATR). The secondary aim was to suggest a clinical VTE risk assessment tool for patients with acute ATR. MethodsFrom 2010–2018, 984 consecutive adults (median age 47yrs, 73% [n = 714/984] male) sustaining an acute ATR were retrospectively identified. Ninety-five percent (n = 939/984) were managed non-operatively in a below-knee cast (52%, n = 507/984) or walking boot (44%, n = 432/984), with 5% (n = 45/984) undergoing primary operative repair (<6wks post-injury). VTE was diagnosed using local medical records and national imaging archives, reviewed at a mean 5yrs (range 1–10) post-injury. Multivariate logistic regression was performed to determine independent factors associated with VTE. ResultsThe incidence of VTE within 90 days of ATR was 3.6% (n = 35/984; deep vein thrombosis 2.1% [n = 21/984], pulmonary embolism 1.9% [n = 19/984]), and the median time to VTE was 24 days (interquartile range 15–44). Age ≥50yrs (adjusted OR [aOR] 2.3, p = 0.027), personal history of VTE/thrombophilia (aOR 6.1, p = 0.009) and family history of VTE (aOR 20.9, p<0.001) were independently associated with VTE following ATR. These non-modifiable risk factors were incorporated into a VTE risk assessment tool. Only 23% of patients developing VTE (n = 8/35) had a relevant personal or family history, but incorporating age ≥50yrs into the VTE risk assessment tool (alongside personal and family history) identified 69% of patients with VTE (n = 24/35). Non weight-bearing for ≥2wks after ATR was also independently associated with VTE (aOR 3.2, p = 0.026). ConclusionsAge ≥50 years, personal history of VTE/thrombophilia and a positive family history were independently associated with VTE following ATR. Incorporating age into our suggested VTE risk assessment tool enhanced its sensitivity in identifying at-risk patients. Early weight-bearing in an appropriate orthosis may be beneficial to all patients in VTE risk reduction.

Outcome of anticoagulation in isolated distal deep vein thrombosis compared to proximal deep venous thrombosis

BackgroundIsolated, distal deep vein thrombosis (IDDVT) is thought to have low rates of propagation, embolization, and recurrence compared with proximal DVT (PDVT), but the data are limited. ObjectivesThe objective of this study was to assess outcomes among patients with IDDVT compared with PDVT. Patients/MethodsConsecutive patients with ultrasound‐confirmed acute DVT (March 1, 2013–August 1, 2020) were identified by reviewing the Mayo Clinic Gonda Vascular Center and VTE Registry databases. Patients were divided into two groups depending on the DVT location (isolated, distal vs. proximal DVT). Outcomes including venous thromboembolism (VTE) recurrence, major bleeding, and death were compared by thrombus location and anticoagulant therapy, warfarin vs. direct oral anticoagulant (DOAC). ResultsIsolated, distal deep vein thrombosis (n = 746) was more often associated with recent surgery, major trauma, or confinement (p < .001), whereas patients with PDVT (n = 1176) were more frequently unprovoked, had a prior history of VTE, or active cancer (p < .001). There was no overall difference in VTE recurrence or major bleeding between groups during follow‐up. Patients with IDDVT had a higher death rate at 3 months (p = .001) and when propensity scored for cancer (p = .003). Independent predictors of mortality included warfarin (vs. DOAC) therapy, increasing age, and active cancer. DOAC therapy resulted in lower VTE recurrence, major bleeding, and death rates in both groups. ConclusionOutcomes of IDDVT including VTE recurrence and bleeding rates were similar to PDVT despite higher early mortality rates. Outcomes for both groups were positively influenced by the use of DOACs.

Safety and Efficacy of Apixaban and Rivaroxaban for the Treatment of Upper Extremity Deep Vein Thrombosis

Background: Patients with upper extremity deep vein thrombosis (UE-DVT) have unique risk factors determining their incidence and recurrence, and were not included in the large clinical trials leading to drug approval for rivaroxaban and apixaban. There is no published data examining the safety or efficacy of direct oral anticoagulants (DOACs) for UE-DVT.Objective: Using the Mayo Clinic registry, we evaluated the safety and effectiveness of rivaroxaban and apixaban for the treatment of UE-DVT.Methods: Consecutive patients treated with rivaroxaban or apixaban for UE-DVT, enrolled into Mayo Clinic Venous Thromboembolism (VTE) Registry between March 1, 2013 and April 30, 2017, were followed prospectively for safety and efficacy. Clinical, demographic and imaging data were collected from each participant at the time of study recruitment. Recurrent VTE, bleeding complications, and death were assessed at 3-month intervals. For subjects unable to return at 3 months, clinical status was assessed by written questionnaire. For unreturned questionnaires, a scripted phone interview was performed. The study was approved by Mayo Clinic Institutional Review Board.Results: Of the 875 subjects with venous thromboembolism in the registry, 37 had UE-DVT and least 3 months of follow up and 20 were treated with rivaroxaban or apixaban. Three subjects had additional sites of VTE other than UE-DVT (1 with pulmonary embolism, 1 with lower extremity deep vein thrombosis, and one with both). The mean age was 57.7 years (standard deviation [SD] 15.2), mean BMI was 30.8 (SD 9.2), and 12 (60.0%) were male (Table 1). Nine (45%) subjects had catheter-associated UE-DVT, 10 (50.0%) had a diagnosis of malignancy, 7 (35.0%) were receiving chemotherapy, 2 (10.0%) had recent surgery (<6 weeks), and 6 had a prior diagnosis of VTE. The mean time from diagnosis of UEDVT to initiation of treatment with rivaroxaban or apixaban was 1.7 days (SD 3.0). At 3 months of follow up, no subjects had recurrent VTE and no subjects had major or minor bleeding episodes. One patient died from underlying malignancy (32 days after starting rivaroxaban).Conclusion: In our ongoing registry of subjects with VTE at Mayo Clinic, treatment of UE-DVT with rivaroxaban or apixaban appears to be safe and effective. Further research and a larger sample size are needed to determine the safety and effectiveness of DOACs for UE-DVT relative to other anticoagulants and lower extremity DVT. [Display omitted] DisclosuresMcBane:Bristol Myers Squibb: Other: Research grant for cancer associated VTE.

Extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: A systematic review and meta-analysis of the literature

BackgroundPostoperative venous thromboembolism (VTE) is a significant source of morbidity and mortality in cancer patients undergoing major abdominopelvic surgery. Many guidelines recommend the use of extended duration postoperative low molecular weight heparin (LMWH) thromboprophylaxis, although the evidence for its overall safety and efficacy is unclear. AimsWe sought to assess the 30-day postoperative rates of VTE and bleeding complications following major abdominopelvic cancer surgery and to explore the potential risks and benefits of extended duration thromboprophylaxis with LMWH in such setting. MethodsA systematic search of the literature was conducted. Observational studies and RCTs of adult patients that underwent abdominopelvic cancer surgery were included. Pooled proportions for the outcome measures and pooled relative risks for the extended duration thromboprophylaxis analyses were generated. ResultsA total of 68 studies (1,631,118 patients) were included in the analysis. The 30-day postoperative rate of VTE was 1.7% (95%CI: 1.5 to 1.9, I2 = 98%). The postoperative rate of clinically-relevant bleeding complications was 3.5% (95%CI: 1.6 to 6.1, I2 = 99%). Extended duration thromboprophylaxis was associated with a significant reduction in the incidence of clinical VTE (1.0% vs 2.1%; Risk ratio (RR) 0.48, 95%CI: 0.31 to 0.74; I2 = 0), without a significant increase in clinically-relevant bleeding (4.0% vs. 4.9%; RR 1.0, 95%CI: 0.66 to 1.5, I2 = 0). ConclusionsThe overall risk of symptomatic VTE within 30 days of surgery was relatively low. Extended LMWH thromboprophylaxis following major abdominopelvic cancer surgery was associated with a reduced incidence of clinical VTE without an increase in clinically-relevant bleeding.

Delayed anticoagulation in venous thromboembolism: Reasons and associated outcomes

ObjectiveWe assessed the number of cases with delayed anticoagulation initiation, explored the reasons for the delay, and its impact on outcome in patients with acute venous thromboembolism (VTE) treated in an organized setting of treatment initiation and continuous, prospective follow‐up. MethodsPatients with anticoagulation initiation delay >24 hours were identified within the cohort of patients with acute VTE enrolled in the Mayo Clinic Venous Thromboembolism Registry between 2013 and 2020. The reasons for treatment delay were explored by reviewing the electronic database. VTE recurrence, all‐cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared to those with no anticoagulation delay. ResultsOf 2378 patients with acute VTE, 100 (4.2%) experienced an anticoagulation delay. We identified seven reasons for treatment delays: deferring anticoagulation initiation to specialists (n = 38), thrombocytopenia (n = 10), planned or recent procedure (n = 16), active or recent bleeding (n = 12), missed diagnosis (n = 7), logistics (n = 6), and patient decision (n = 4). In seven cases, no reason was identified. We identified modifiable reasons for anticoagulation delay in 55%. At 90‐day follow‐up, patients with anticoagulation delay had a higher rate of mortality and major bleeding. VTE recurrence and CRNMB were not statistically different compared to those without anticoagulation delay. After adjustment for age, weight, and cancer, hazard ratios (HRs) for VTE recurrence and major bleeding remained elevated but not to a statistically significant level. ConclusionIn the setting of a highly organized system of anticoagulation initiation, the incidence of treatment delay is low. Yet most delays could be avoided. A low number of cases provide insufficient power to evaluate the clinical consequences of anticoagulation initiation delay; however, elevated HR for VTE recurrence and major bleeding suggest association and need for further investigation.

A Weight- and Anti-Xa-Guided Enoxaparin Dosing Protocol for venous thromboembolism Prophylaxis in intensive care unit Trauma Patients

Trauma patients are high risk for venous thromboembolism (VTE) and the optimal dosing strategy for prophylactic enoxaparin remains unknown. The purpose of this quality improvement project was to evaluate a weight-based and anti-Xa-guided enoxaparin dosing protocol in intensive care unit (ICU) trauma patients and to determine if the protocol led to reduced clinical VTE rates. Adult trauma patients admitted for ≥ 48 hours to our surgical or neurosurgical ICUs who received ≥ 3 consecutive weight-based enoxaparin doses were eligible for inclusion into this pre-post implementation cohort study. Enoxaparin 30 mg every 12 hours was used for weight 50 to 100 kg and body mass index (BMI) < 40 kg/m2 and enoxaparin 40 mg every 12 hours for weight ≥ 100 kg or BMI ≥ 40 kg/m2. PRE cohort patients did not routinely receive anti-Xa level monitoring, while in the POST cohort, dosing was subsequently titrated to peak anti-Xa levels of 0.2 to 0.4 IU/mL. A total of 110 and 113 patients were included in the PRE and POST cohorts, respectively. Clinical VTE rates were similar between groups. In the POST cohort, 75% of patients achieved goal anti-Xa levels without dose titrations, while 12% of higher weight patients and 9.1% of lower weight patients required adjustment. When comparing weight quartiles, patients > 100 kg were more likely to have sub-prophylactic anti-Xa levels than those ≤ 69 kg. Our enoxaparin dosing protocol was safe and frequently achieved initial anti-Xa levels within goal, indicating that weight-based dosing alone may be sufficient. However, patients > 100 kg may benefit from anti-Xa monitoring as they are highest risk for sub-prophylactic levels despite higher initial enoxaparin dosing.

Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study

ObjectivesFor the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre...

Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019.

BackgroundSARS-CoV-2 infection is associated with hypercoagulability which predisposes to venous thromboembolism (VTE).We analyzed platelet and neutrophil activation in COVID-19 patients and their association with VTE.MethodsHospitalized COVID-19 patients and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase-9 (MMP-9), a neutrophil-released enzyme, were measured. Four patients were re-studied after recovery. The activating effect of COVID-19 plasma on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied.Results36 COVID-19 patients and 31 healthy controls were studied; 8/36 COVID-19 patients (22.2%) developed VTE. Platelets and neutrophils were activated in COVID-19 patients. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic MMP-9 was significantly increased in COVID-19 patients.Platelet and neutrophil activation markers, but less so NETs, normalized after recovery.In vitro, plasma from COVID-19 patients triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic dose low-molecular weight heparin, but not by aspirin or dypiridamole.ConclusionsPlatelet and neutrophil activation are key features of COVID-19 patients. NET biomarkers may help to predict clinical worsening and VTE, and may guide LMWH-treatment intensity.

Association between Cancer and Anatomical Site of Venous Thromboembolic Disease

Background:There is limited published data on the association between malignancy and the location of venous thromboembolism (VTE) in the body. Aims:Assess the location of VTE in the body in patients with active cancer and compare these results in patients without malignancy. Methods:Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013 and November 30, 2019 for acute VTE were followed prospectively. Anatomical site of thrombosis and malignancy status were recorded. Patient outcomes were assessed in person, by mailed questionnaire, or by a scripted phone interview. Active cancer was defined as treatment for malignancy within the last six months or not yet in remission. Results:During the study period there were 2,798 patients with acute VTE (1256 with and 1542 without active cancer). Pulmonary emboli were more common in patients with active cancer compared to patients without cancer (49.5% vs. 39.7%, p&amp;lt;0.001). Upper extremity deep vein thrombosis (11.4 % vs. 7.7%, p&amp;lt;0.001), renal vein thrombi (1.4% vs. 0.2%, p&amp;lt;0.001) and splanchnic vein thrombi (9.3% vs. 6.0%, p=0.001) were all more common in patients with active cancer compared to patients without cancer. Conclusion:Compared to those without malignancy, patients with active cancer were more likely to have pulmonary emboli, upper extremity deep vein thrombosis, renal vein thrombi, and splanchnic vein thrombi. Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of Dabigatran in the Treatment and Secondary Prophylaxis of Children with Venous Thromboembolism and Thrombophilia

Background: Thrombophilia in children is characterized by hypercoagulability and increased frequency of thrombotic events (Young G, et al. Circulation. 2008;118:1373-1378; Kenet G, et al. Circulation. 2010;121:1838-1847). Recently, phase IIb/III clinical trials in children with venous thromboembolism (VTE) have reported the non-inferiority of dabigatran etexilate (DE) versus standard of care (SOC) for the treatment of acute VTE (Albisetti M, et al. ISTH 2019, Abstract OC 57.3), and a favorable safety profile for DE in secondary VTE prevention in children with persistent VTE risk factor(s) (Brandão LR, et al. Blood. 2020;135:491-504). Aims: To perform a subgroup analysis evaluating the efficacy and safety of DE for the treatment and secondary prophylaxis of VTE in children with thrombophilia in the phase IIb/III DE clinical trials. Methods: In the open-label, phase IIb/III DIVERSITY trial (NCT01895777), children aged from birth to &amp;lt; 18 years (yrs) with an objectively confirmed VTE diagnosis (by imaging studies) initially treated with unfractionated heparin or low-molecular-weight heparin were randomized (2:1) to receive up to 3 months of DE or SOC. Primary composite efficacy endpoint: complete thrombus resolution and freedom from VTE recurrence, or VTE-related death. Safety endpoints included bleeding events (BEs). The open-label, phase III, secondary VTE prevention trial (NCT02197416) treated children aged from &amp;gt; 3 months to &amp;lt; 18 yrs with DE for up to 12 months or less, if the identified VTE clinical risk factor resolved. Eligible children had an objectively confirmed diagnosis of VTE treated with SOC for ≥ 3 months, or had completed DE or SOC treatment in DIVERSITY and had an unresolved clinical VTE risk factor requiring further anticoagulation. Primary endpoints included VTE recurrence and BEs. Thrombophilia status was confirmed according to the definitions used by the local experts. Results: In DIVERSITY, 23.2% of children had thrombophilia; demographics were comparable to the overall population, although they were slightly older (mean [standard deviation] age 13.2 [4.9] vs 11.1 [6.1] years in the overall population; p = 0.005). In children with thrombophilia, DE was found to be non-inferior to SOC for the primary endpoint (similar to the overall population), and more children treated with DE achieved the composite primary endpoint than with SOC (SOC 21.7% vs DE 35.9%; Mantel-Hänszel-weighted difference in rates for SOC minus DE [90% CI] −0.14 [−0.32 to 0.05]; p for non-inferiority = 0.0014), similar to the overall population (Table). Regardless of treatment, VTE recurrence appeared higher in children with thrombophilia than in the overall population, with numerically fewer VTE recurrences reported by children with thrombophilia treated with DE (7.7%) versus SOC (21.7%), although this was not significantly lower (p = 0.13). Numerical differences in residual thrombotic burden between SOC vs DE seen in the overall population appeared to be amplified in children with thrombophilia. Numerically fewer children with thrombophilia treated with DE reported thrombus progression (SOC 13.0% vs DE 5.1%) or stabilization (21.7% vs 10.3%), while more reported partial (34.8% vs 43.6%) or complete thrombus resolution (21.7% vs 35.9%). In the thrombophilia subgroup, BEs appeared to be lower in children treated with DE (SOC 26.1% vs DE 17.9%), while in the overall population BEs with SOC and DE were comparable. In the secondary VTE prevention trial, children with thrombophilia were also slightly older versus the overall population (mean [standard deviation] age 14.1 [3.6] vs 12.8 [4.6] yrs; p = 0.006). In this larger subgroup of children, rates of recurrent VTE at 12 months appeared to be higher in the thrombophilia group (2.8%) compared to the overall population (1.4%) (Table), with BEs largely comparable (27.4% and 22.5%, respectively). Conclusions: Unsurprisingly, numerically more children with thrombophilia appeared to report VTE recurrence, and in DIVERSITY thrombus progression/stabilization also seemed higher compared with the overall population. Compared with the overall populations, these subgroup analyses showed consistent results for DE in children with acute VTE and thrombophilia in the DIVERSITY trial, along with a favorable safety profile of DE for secondary VTE prevention. Disclosures Brandao: Boehringer Ingelheim: Other: Member of a paediatric expert working group. Tartakovsky:Boehringer Ingelheim: Current Employment. Albisetti:Boehringer Ingelheim: Other: Member of a paediatric expert working group; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Bomgaars:Boehringer Ingelheim: Other: Member of a paediatric expert working group. Chalmers:CSL Behring: Honoraria; Shire/Takeda: Honoraria; Boehringer Ingelheim: Other: Member of a paediatric expert working group; Grifols: Honoraria; Roche: Honoraria; Sobi: Honoraria; Bristol-Myers Squibb: Honoraria. Mitchell:Boehringer Ingelheim: Other: Member of a paediatric expert working group. Luciani:Boehringer Ingelheim: Other: Member of a paediatric expert working group. Lvova:Boehringer Ingelheim: Honoraria. Simetzberger:Boehringer Ingelheim: Current Employment. Sun:Boehringer Ingelheim: Current Employment. Gergei:Boehringer Ingelheim: Current Employment. Brueckmann:Boehringer Ingelheim: Current Employment. Halton:Boehringer Ingelheim: Other: Member of a paediatric expert working group. OffLabel Disclosure: dabigatran etexilate in paediatric VTE

Establishing diagnostic criteria and treatment of subsegmental pulmonary embolism: A Delphi analysis of experts

BackgroundImproved imaging techniques have increased the incidence of subsegmental pulmonary embolism (ssPE). Indirect evidence is suggesting that ssPE may represent a more benign presentation of venous thromboembolism not necessarily requiring anticoagulant treatment. However, correctly diagnosing ssPE is challenging with reported low interobserver agreement, partly due to the lack of widely accepted diagnostic criteria. ObjectivesWe sought to derive uniform diagnostic criteria for ssPE, guided by expert consensus. MethodsBased on an extensive literature review and expert opinion of a Delphi steering committee, two surveys including statements regarding diagnostic criteria and management options for ssPE were established. These surveys were conducted electronically among two panels, respectively: expert thoracic radiologists and clinical venous thromboembolism specialists. The Delphi method was used to achieve consensus after multiple survey rounds. Consensus was defined as a level of agreement >70%. ResultsTwenty‐nine of 40 invited radiologists (73%) and 40 of 51 clinicians (78%) participated. Following two survey rounds by the expert radiologists, consensus was achieved on 15 of 16 statements, including on the established diagnostic criteria for ssPE (96% agreement): a contrast defect in a subsegmental artery, that is, the first arterial branch division of any segmental artery independent of artery diameter, visible in at least two subsequent axial slices, using a computed tomography scanner with a desired maximum collimator width of ≤1 mm. These criteria were approved by 83% of the clinical venous thromboembolism (VTE) specialists. The clinical expert panel favored anticoagulant treatment in case of prior VTE, antiphospholipid syndrome, pregnancy, cancer, and proximal deep vein thrombosis. ConclusionThe results of this analysis provide standard radiological criteria for ssPE that may be applicable in both clinical trials and practice.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight<60kg, 60-120kg, and>120kg. Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. Among 2577 patients with weight ranging from 27.0kg to 263.2kg, 2123 (82%) had a bodyweight between 60 and 120kg, 223 (8.7%) had bodyweight<60kg, and 230 (8.9%) had bodyweight>120kg. Patients with bodyweight<60kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P=.03, and 4.4% vs 1.4%, P=.05, respectively). Patients with bodyweight>120kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P=.01). Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight<60kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight>120kg on rivaroxaban.

Impact of Tumor Genomic Mutations on Thrombotic Risk in Cancer Patients.

Venous thromboembolism (VTE) is common in patients with cancer and is an important contributor to morbidity and mortality in these patients. Early thromboprophylaxis initiated only in those cancer patients at highest risk for VTE would be optimal. Risk stratification scores incorporating tumor location, laboratory values and patient characteristics have attempted to identify those patients most likely to benefit from thromboprophylaxis but even well-validated scores are not able to reliably distinguish the highest-risk patients. Recognizing that tumor genetics affect the biology and behavior of malignancies, recent studies have explored the impact of specific molecular aberrations on the rate of VTE in cancer patients. The presence of certain molecular aberrations in a variety of different cancers, including lung, colon, brain and hematologic tumors, have been associated with an increased risk of VTE and arterial thrombotic events. This review examines the findings of these studies and discusses the implications of these findings on decisions relating to thromboprophylaxis use in the clinical setting. Ultimately, the integration of tumor molecular genomic information into clinical VTE risk stratification scores in cancer patients may prove to be a major advancement in the prevention of cancer-associated thrombosis.

The expression level of COX7C associates with venous thromboembolism in colon cancer patients.

Venous thromboembolism (VTE) is a common complication of colon cancer. In the present study, we aimed to explore the association of the oncogene COX7C to VTE in colon cancer patients. Samples from 580 patients were examined histologically for VTE and pathological characteristic of cancer. Gene mutation and expression analysis were performed using polymerase chain reaction-based assays to evaluate genes related to VTE, including COX7C. Univariate analysis between clinical pathological factors and VTE was conducted. Logistic regression analysis was performed for the prediction of VTE by pathological factors and gene expressions. Among patients investigated, a total of 56 patients had VTE. COX7C had a significant correlation with VTE (p < 0.001). Despite a correlation between tumor size, invasion depth of tumor, lymph node metastasis, lymph node metastasis, distant metastasis, lymphovascular invasion, histologic type and pathology type, Ki-67, and some other genes, to VTE (p > 0.05), only COX7C expression demonstrated significance in its ability to predict VTE. Here, we show that COX7C upregulation strongly correlates with VTE in colon cancer, which implicates its role as a biomarker and therapeutic target of VTE in colon cancer.

Nurses' knowledge, attitudes, and behaviors toward venous thromboembolism prophylaxis: How to do better.

To investigate the cognition of nurses on the control and treatment of venous thromboembolism in China, thereby providing suitable countermeasures for clinical venous thromboembolism prophylaxis and treatment. In December 2019, a total of 1121 registered nurses from a university-affiliated hospital were selected to answer the self-designed and electronic questionnaire (Wenquanxing: www.wjx.cn/), which was designed to evaluate the nurses' knowledge (21 items), attitudes (6 items), and behaviors (9 items) toward venous thromboembolism prophylaxis. Descriptive, correlation, and regression analyses were conducted for data analysis. Of the included 1121 nurses, only 55.43% nurses selected 100% correct answer. The influencing factors of knowledge included the department, education, professional ranks, and venous thromboembolism nursing experience. The nurses from ICU department gained the highest score, but the nurses from pediatrics department obtained the lowest score. The nurses with higher education level and professional ranks, and nursing experiences achieved higher scores. The total positive response rate for the attitude-related items was 68.54%. Nurses were primarily concerned about the financial penalty due to the inability to complete the work (49.0%). An increasing workload is the second primary concern of nurses (40.8%). The increasing medical cost, extension of hospital stay, and exacerbation of doctor-patient conflicts were the most serious difficulties involved in venous thromboembolism prophylaxis. The total correct score rate for the behaviors was 56.19%. Nearly half of the nurses could not offer advice for venous thromboembolism patients. The nursing experience, department, and years of work were related to the scores of knowledge-related items (all P < 0.05). The overall knowledge level of the nurses was not optimistic. Although their general attitude toward venous thromboembolism prophylaxis was positive, their behaviors were influenced by many factors. Administrators should, therefore, make countermeasures to deal with these problems.