Recurrent VTE Research Articles

Abstract 256: Discharging Low-risk Pulmonary Embolism From An Emergency Room

Background and Objectives: Patients with PE are traditionally admitted on parenteral agents, despite increasing literature that sPESI negative patients can be safely discharged from the ED. Our quality improvement initiative is focused on outpatient treatment for ED-diagnosed pulmonary emboli (OTPE) and our objective is to assess LOS, readmissions and to describe findings of our follow-up phone calls. Methods: This is an actively enrolling prospective study from 7/2020 at a single site with >500 PE cases per year with a PE Response Team (PERT). All ED PE patients are screened for OTPE. Exclusion criteria include sPESI ≥ 1, ESC high or intermediate, bleeding ≤ 30 days, hemoglobin < 8, platelet < 50,000, pregnancy, prior VTE, concomitant COVID-19, recent major surgery and social factors. Patients identified are discussed with PERT and ED physicians. If agreed upon, patients are discharged on DOAC with follow-up within one week. Patients receive calls on days 3, 7, and 30 from the OTPE team to assess AE relating to the DOAC or PE. LOS metrics are reported as mean with standard deviations, and readmissions are reported as percentages. Results: Ninety-eight low-risk patients were identified, of which 50 were OTPE-eligible with mean age 44.5 ± 16.9 years of age and 58% female. When comparing OTPE to low-risk admissions, there are no differences in age (p=0.35) and sex (p=0.72). For OTPE, the follow-up calls on day 3, 7, and 30 revealed no patient reported recurrent VTE, major bleeding or death. There was a similar ED provider to disposition LOS (p=0.74). Low-risk admissions had a higher rate of readmission than OTPE (p=0.19). Conclusion: Our OTPE process does not increase ED provider to disposition LOS, readmissions, or adverse outcomes. Future work will examine financial implications of OTPE and barriers to adoption of the process. As this is actively enrolling quality improvement initiative, we will continue to track post-implementation to optimize our process.

OC-16: Comparison of VTE recurrence, bleeding-related hospitalization and all-cause mortality in patients with active cancer in two patient populations, based upon cancer types considered to have high and low risks of bleeding, receiving DOACs or LMWH: The OSCAR UK Study

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No VTE Recurrence After 1-Year Follow-Up of Hospitalized Patients With COVID-19 and a VTE Event: A Prospective Study

No VTE Recurrence After 1-Year Follow-Up of Hospitalized Patients With COVID-19 and a VTE Event: A Prospective Study

Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: The RIETECAT study

BackgroundVenous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. ObjectivesThe objective of the RIETECAT study was to compare the long‐term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. MethodsWe used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. ResultsFrom January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48‐1.38), major bleeding (aHR, 1.40; 95% CI, 0.80‐2.46), or death (aHR, 1.07; 95% CI, 0.88‐1.30) between subgroups. ConclusionsIn RIETECAT, in patients with cancer and VTE receiving full‐dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6‐month period.

Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial

BackgroundVenous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive. Procoagulant phospholipids (PPL), and phosphatidylserine in particular, are crucial for efficient coagulation activation, but no studies have investigated the effect of statin treatment on plasma PPL activity. ObjectivesTo investigate the impact of rosuvastatin treatment on plasma PPL activity and levels of extracellular vesicles (EVs). Patients/MethodsPatients with a history of VTE (≥18 years) allowed to stop anticoagulant treatment were randomized to either 20 mg/day of rosuvastatin treatment or no treatment for 28 days in the Statins Reduce Thrombophilia (NCT01613794) trial. Plasma samples were collected at baseline and study end. PPL activity was measured in samples from 245 participants using a factor Xa‐dependent clotting assay and EV levels by flow cytometry. ResultsRosuvastatin treatment yielded an overall 22% (95% confidence interval [CI] −38.2 to −5.8) reduction in PPL activity, and 37% (95% CI −62.9 to −11.2) reduction in PPL activity in participants with a history of pulmonary embolism. The effect of rosuvastatin on plasma PPL activity was not explained by changes in total cholesterol nor change in levels of total‐ or platelet‐derived EVs. ConclusionsRosuvastatin treatment caused a substantial decrease in plasma PPL activity, suggesting that a PPL‐dependent attenuation of coagulation activation may contribute to a reduced VTE risk following statin treatment.

Management of cancer‐associated thrombosis with thrombocytopenia: Impact of the ISTH guidance statement

BackgroundOptimal management of cancer‐associated thrombosis (CAT) in patients with thrombocytopenia remains difficult given competing risks of recurrent thrombosis and increased bleeding. We determine the impact of the ISTH Scientific and Standardization Committee (SCC) guidance on CAT management and thrombocytopenia on platelet transfusion, bleeding, and recurrent thrombosis. MethodsA retrospective review was performed of patients with CAT and thrombocytopenia who required anticoagulation for VTE for 11 months before and after implementation of the ISTH SCC guidance. Medical records were reviewed to identify the type of VTE event, number of platelet transfusions, incidence of bleeding, and VTE recurrence within pre‐ and postintervention time periods. ResultsA total of 41 and 80 cases were included in the preintervention and postintervention periods, respectively. The preintervention group showed a trend toward less acute VTE events (39% vs 55%; P= .05). The postintervention period had an increased per‐patient platelet transfusion (median, 2.5 vs 4; P= .05). Nonmajor bleeding was increased in the postintervention group (2% vs 16%; P= 0.03) and included all six (8%) major hemorrhages (P= .09). There was numerically less recurrent thrombosis in the postintervention group (20% vs 8%; P= .07), which was not significantly different when accounting for acuity of VTE. Management adherence was strong, at 91%, in the postintervention group. ConclusionThe ISTH guidance on management of cancer‐associated thrombosis in patients with thrombocytopenia was successfully implemented in an academic medical center. There was no significant difference in bleeding or recurrent thrombosis outcomes after adjusting for acuity of VTE.

Direct oral anticoagulant vs low molecular weight heparin for the treatment of venous thromboembolism associated with malignancy: a meta- analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients and treatment of cancer associated thromboembolism is challenging. Low molecular weight heparin (LMWH) has been the standard of care treatment for cancer-associated VTE yet the use of direct oral anticoagulant (DOACs) has been promising. Purpose To determine the efficacy and safety between direct oral anticoagulants compared to low molecular weight heparin in recurrent VTE prevention cancer associated thromboembolism. Method Randomized controlled trials (RCT) comparing DOACs with LMWH for treatment of VTE in cancer patients. Results Four randomized controlled trials were selected which included a total of 2,894 participants enrolled in 4 randomized controlled trials, with a mean follow-up of 6-12 months. As a pooled aggregate, oral anticoagulant is beneficial over dalteparin in the prevention of recurrent VTE. (RR 0.75; 95% CI, 0.59-0.95; I2 59%). The safety of oral anticoagulant compared to dalteparin, there was statistically no significant difference in the major bleeding risk. (RR 1.35; 95% CI, 0.93-1.94; I2 28%). Sub-group analysis of clinically relevant non major bleeding however favors the dalteparin over oral anticoagulant. (RR 1.59; 95% CI, 1.23-2.05; I2 41%). Conclusion In this meta-analysis, the efficacy of direct oral anticoagulant in terms of recurrent VTE prevention for patients with cancer is favorable or at least similar to that of dalteparin. Though safety profile has no significant difference in terms of major bleeding between the two groups, oral anticoagulants has a higher risk of clinically non-major bleeding. Abstract Figure. Forest plot for recurrent VTE Abstract Figure. Forest plot for major bleeding

Abstract TMP74: Direct Oral Anticoagulants Vs. Vitamin K Antagonists In Patients With Cerebral Venous Thrombosis: A Systematic Review And Meta-analysis

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

Prognostic impact of acute kidney injury in patients with acute pulmonary embolism data from the RIETE registry.

Risk stratification is recommended for patients with pulmonary embolism (PE), and usually starts with the assessment of the hemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI). The influence of acute kidney injury (AKI) on the prognostic stratification has not been evaluated according to the "Kidney Disease: Improving Global Outcomes" (KDIGO). AKI was computed according to the KDIGO definition in patients with acute PE in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Patients with hemodynamic instability were considered high-risk. Normotensive patients were stratified according to the sPESI score (low-risk: sPESI = 0; intermediate-risk: sPESI > 0). The primary outcome was all-cause 30-day mortality. Secondary outcomes were major bleeding and VTE recurrences during the same period. Among 30,532 patients with PE, 1108 (3.6%) were classified to be at high-risk, 10,577 (34.6%) at low-risk, and the remaining 18,847 (61.8%) at intermediate-risk of adverse events. At baseline, 7879 (26%) had AKI. Overall, 1543 of 30,532 patients (5.1%) died within the first 30days. The presence of AKI was associated with increased mortality rates in all subgroups of patients: in those at low-risk it increased from 0.46 to 3%, in intermediate-risk from 5.4 to 10%, and inhigh-risk patients from 9.4 to 18%. The presence of AKI was also associated with an increased risk of major bleeding in all subgroups. The addition of the AKI status to the sPESI score improved the prediction of the 30-day mortality and may be particularly helpful for decisions such as identification of low-risk patient for home discharge.

Validation of a predictive model for identifying an increased risk for recurrence in adolescents and young adults with a first provoked thromboembolism

BackgroundTo develop and validate a predictive model to determinate patients at increased risk to suffer from recurrence following a first provoked deep vein thrombosis (VTE).Methods: Predictive variables, i.e. male sex [1 point], inherited thrombophilia (IT) status (none [0 points], single [1 point], combined variants [2 points]), blood group non-0, and age at first VTE onset were included into a risk assessment model, which was derived in 511 patients and then validated in 509 independent subjects. ResultsVTE recurrence risk score (maximum 4 points, range 0–3) was below two for patients scored as low-risk (LRS) and ≥2 for patients at high-risk (HRS). Within a median time of 3 years after withdrawal of anticoagulation (AC) recurrence rate in LRG (derivation) was 11.8% versus 26.0% in HRS (p < 0.001). In the validation cohort within 2.2 years the recurrence rate was 9.8% in LRS versus 30.1% in HRS (p < 0.001). In multivariable analysis adjusted for age at first VTE and blood group the recurrent risk in HRS was significantly increased compared with the LRS (derivation: hazard/95% confidence interval: 3.7/1.75–7.91; validation: 4.7/2.24–9.81; combined 5.2/1.92–13.9). Model specificity (sensitivity) was 79.0% (52.0%) in the derivation cohort compared with 78.0% (43.0%) in the validation group.In conclusion, in the prediction model presented here the risk of VTE recurrence was associated with male gender and combined ITs. Based on the negative predictive value calculated the model may identify patients with a first provoked VTE not being at risk for recurrence.

A RIETE registry analysis of patients with upper extremity deep vein thrombosis and thoracic outlet syndrome

BackgroundUpper extremity deep vein thrombosis (UEDVT) related to thoracic outlet syndrome (TOS) is rare, and the literature is limited to institutional case series. MethodsWe used data from the RIETE Registry to compare outcomes (recurrences, major bleeding and signs and symptoms of post-thrombotic [PTS] syndrome) in patients with UEDVT and TOS undergoing first rib resection vs. those not undergoing surgery. ResultsFrom March 2001 to March 2021, there were 4214 patients with UEDVT, of whom 209 (4.96%) had TOS. Of these, 55 (26%) underwent first rib resection. Patients with TOS were younger and less likely to have comorbidities than those without TOS. There were no differences between patients with TOS undergoing surgery and those who did not. During anticoagulation, patients with TOS had a non-statistically significant lower rate of VTE recurrences than those without TOS (hazard ratio [HR]: 0.46; 95%CI: 0.14–1.12) and a lower bleeding rate (HR: 0.16; 95%CI: 0.01–0.83). No patient with TOS developed pulmonary embolism or died. Patients with TOS undergoing surgery had fewer PTS symptoms (odds ratio [OR]: 0.21; 95%CI: 0.06–0.68) or signs (OR: 0.11; 95%CI: 0.02–0.42) after one year than patients who did not have surgery. At two years, the differences in symptoms (OR: 0.25; 95%CI: 0.06–0.94) and signs (OR: 0.04; 95%CI: 0.002–0.33) persisted. ConclusionsPatients with UEDVT and TOS were younger and had less comorbidities than those without. Surgical resection of the first rib was associated with a lower proportion of patients developing PTS one and two years later.

Factor Xa inhibitors versus low molecular weight heparin for the treatment of cancer associated venous thromboembolism; A meta-analysis of randomized controlled trials and non-randomized studies.

We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

Abstract 11055: Length of Anticoagulation Treatment in Provoked VTE - Lessons from the Maqi 2 Collaborative

Introduction: Anticoagulation (AC) with warfarin or direct oral anticoagulants (DOAC) is the core of VTE treatment. Due to lower risk of VTE recurrence, American College of Chest Physicians (ACCP) recommends three months AC in patients with provoked VTE and without other indication for long-term AC. We aimed to assess how closely “real world” practice followed guideline recommendations. Hypothesis: We hypothesize most patients taking warfarin or DOAC for provoked VTE receive no more than three months AC. Patients who get prolonged AC are more likely to be taking DOAC than warfarin. Methods: We identified patients who initiated warfarin or DOAC from a six center AC clinic registry between 2008-20. Provoked VTE was defined as VTE after a transient risk factor: surgery, lower extremity cast/immobilization, childbirth, or OCPs. AC duration was categorized as &lt;80, 80-120, or &gt;120 days. Appropriate treatment window was defined as 80-120 days to adjust for variability in clinic scheduling. Median AC length for DOAC vs. warfarin was compared with a two-sample test. Prevalence of extended AC was compared using chi-square test. Variables increasing risk of extended AC were analyzed with logistic regression, adjusted for baseline demographic and clinical characteristics. Results: At six centers, we identified 488 patients with provoked VTE on warfarin and 302 on DOAC. Average AC length was 137 days for warfarin and 180 days for DOAC (p&lt;0.0001). 266 (54.5%) patients on warfarin and 215 (71.2%) on DOAC got &gt;120 days of AC (p&lt;0.001). Variables increasing risk of &gt;120 days AC include recurrent VTE (OR 2.11; CI 1.34,3.32), prior MI (OR 4.09; CI 1.37,12.2), and DOAC use (OR 2.34; CI 1.69, 3.23) (Figure 1). Conclusions: In this multi-center analysis, most patients receive AC longer than guideline-recommended. DOAC use, recurrent VTE, and prior MI are associated with prolonged AC. Understanding the relationship between prior MI and AC duration in provoked VTE warrants future investigation.

Rate of Clonal Hematopoiesis in Patients with Venous Thromboembolism

BackgroundVenous thromboembolism (VTE) is the third most common cardiovascular disease with an incidence over 1% in the elderly. About 50% of VTE is unprovoked, which is associated with higher rates of recurrent VTE and complications such as post-thrombotic syndrome. Clonal hematopoiesis (CH) refers to recurrent somatic mutations associated with hematologic malignancies that are present in otherwise healthy individuals. CH is more common with increased age, occurring in more than 10% of people over the age of 70 and has been associated with an increased risk of coronary artery disease. The rates of CH in patients with VTE or complications arising from this is not known.MethodsAdult patients (age ≥ 18) with VTE were enrolled at the Ohio State University Thrombosis Clinic between 2017 and 2020. Clinical data was obtained at the time of routine clinic follow-up or ad hoc, and a research blood sample was collected with routine blood work. DNA extracted from peripheral blood mononuclear cells were analyzed for the presence of CH via error corrected next generation sequencing (NGS) using the Ion Gene Studio S5 System. A custom AmpliSeq panel IAH150087 was designed to detect CH, which included whole gene sequencing and hotspots in 25 common genes associated with myeloid malignancies, including DNMT3A, TET2, ASXL1, among others, with a sequencing depth of up to 50,000X. Data was collected and analyzed using Ion Torrent S5/GS-S5 Instrument with Torrent Suite 5.12.0 version. Final analysis of sequence data was performed using combination of software: Variant Caller v.5.12.10-1, IGV5.01 (0) and Ion Reporter v.5.12.3.0. The hg19 reference sequence was used to assess for deviation. CH was defined as a variable allele frequency ≥ 2%. Two sample t-test and chi-square test were used to compare patients with and without CH for continuous and categorical variables, respectively.ResultsA total of 167 patients are included the study. Median age is 60.3 years and 55% of patients are female. 80% of patients are white. The majority of patients have unprovoked VTE (81%); 23 patients (13.8%) have VTE associated with cancer. 84% of patients were treated with a direct oral anticoagulant. Over the median follow-up duration of 400 days, 7 patients had recurrent VTE and 19 patients had a total of 21 bleeding events (7 major bleeding and 14 clinically relevant non-major bleeding [CRNMB] by ISTH criteria).Overall, 22 patients (13.2%) have detectable CH. Patients with CH are significantly older than those without CH (mean age 70 vs 59, p <0.0001). There is a trend towards increased CH rate in male patients (17% of male patients vs 10% of female patients with CH). There are no other differences in baseline characteristics among patients with and without CH, including type or location of VTE or cancer status. Among the 144 VTE patients without cancer, the median age is 60 years old and the CH rate is also 13.2%. In this group, the mean age of patients with CH is 12 years older than those without CH (70.5 years vs 58.4 years, p <0.0001). No other significant baseline characteristics are noted.30 distinct CH mutations are noted in these 22 patients. Most patients have a single gene mutation (77%). Gene mutations in DNMT3A are the most common (46%), followed by TET2 (13%), and PPM1D (10%) (see figure). Most mutations are missense (57%), followed by nonsense (30%) and insertion/deletion mutations (13%). One patient has a JAK2 V617F mutation without known history of myeloproliferative disease. 8 CH patients with serial samples collected over a median duration of 136 days (range 91 - 490 days) showed no significant change in CH clone size over time.Patients with CH have no differences in rates of recurrent VTE or arterial thrombosis compared to those without CH. Patients with CH have a trend towards increased rate of combined major bleeding and CRNMB events (23% vs 10%, p=0.14). Patients with CH also had a trend towards increased mean corpuscular volume (MCV) (mean 93.5 vs 90.7, p=0.13), although no other cytopenias or differences in complete blood count parameters were noted.ConclusionThe CH rate in patients with VTE was not found to be much higher than what might be expected by age alone. We found no change in the CH rate after excluding cancer patients. A larger VTE population with age-matched controls will better determine the CH rate in patients with VTE. CH can be a consideration in designing future clinical VTE studies that assess bleeding risk. [Display omitted] DisclosuresByrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

DIRECT ORAL ANTICOAGULANTS IN SICKLE CELL DISEASE, WHERE WE STAND AND WHERE WE ARE HEADING: A SYSTEMATIC REVIEW

The evidence guiding VTE management in SCD, specifically in terms of anticoagulant choice, is scarce. Therefore, we conducted a systematic review that evaluates the effectiveness and safety of direct oral anticoagulants (DOACs) in SCD with VTE. We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the English literature (PubMed, SCOPUS, and Google Scholar) for randomized controlled trials, observational studies, reviews, case series, and case reports for patients with SCD treated with DOAC for thromboembolic disease. The current data demonstrated that the use of DOACs for VTE in SCD has similar effectiveness in the prevention of VTE recurrence in comparison to other anticoagulants, including VKAs and injectable anticoagulants with a better safety profile. However, given the absence of clinical practice guidelines for the treatment of VTE among patients with SCD, the clinical practice guidelines recommendations for VTE treatment can be applied to patients with SCD. In view of the current evidence and based on the results observed; using DOACs was associated with lesser bleeding incidence and fewer complications comparing to VKAs. We think it is rational to use DOACs for VTE treatment among patients with SCD rather than use VKAs.

The use of direct oral anticoagulants for thromboprophylaxis or treatment of cancer-associated venous thromboembolism: a meta-analysis and review of the guidelines

BackgroundVenous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines’ recommendations.MethodsMEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs.ResultsFour studies evaluating DOACs use for thromboprophylaxis and four – for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24).ConclusionsThe DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient’s risk of VTE and bleeding.

Direct oral anticoagulants or low-molecular-weight heparins for venous thromboembolism in patients with brain tumors

IntroductionPatients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. Materials & methodsIn this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. ResultsBetween January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74–13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5–14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2–25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5–41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5–14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7–16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. ConclusionThere were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.

Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study

AbstractVenous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multicenter, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count <100 000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at 6 hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%) and 33 (27%) with modified-dose anticoagulation; 13 (11%) patients received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33 [94%]) and an acute deep vein thrombosis (28 of 33 [85%]). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% confidence interval [CI], 4.9-20.8) and 6.6% (95% CI, 2.4-15.7) in those who received modified-dose anticoagulation (Fine-Gray hazard ratio, 2.18; 95% CI, 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop deep vein thrombosis in the setting of thrombocytopenia.

Effectiveness and safety of apixaban vs warfarin among older venous thromboembolism patients: a subgroup analysis of age

Abstract Background Venous thromboembolism (VTE) is the third most common cardiovascular condition in adult patients. Older patients are at an increased risk of VTE. However, they have been underrepresented in clinical trials and evidence on the safety and effectiveness of anticoagulants in older VTE patients, especially very elderly patients (≥80 years), is sparse. Purpose To evaluate the risk of recurrent VTE, major bleeding (MB), and clinically relevant non-major (CRNM) bleeding among older VTE patients initiating apixaban or warfarin according to two age sub-groups: 65–79 and ≥80 years. Methods Older VTE patients (aged ≥65 years) who initiated apixaban or warfarin were identified from the CMS Medicare database (September 2014–December 2017). To balance the characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting (IPTW) was conducted. Post IPTW, a subgroup interaction analysis was conducted to evaluate if there was any difference in treatment effects between the two age subgroups (65–79 vs. ≥80) on recurrent VTE, MB, and CRNM bleeding. Cox proportional hazard models were used to conduct the interaction analysis, and the statistical significance of the interaction was set to p-value &amp;lt;0.10. Results A total of 22,135 apixaban and 45,840 warfarin patients with VTE aged ≥65 years were eligible for analysis. Post IPTW, patient characteristics were balanced between the apixaban and warfarin treatment cohorts. Apixaban patients had significantly lower risk of recurrent VTE, MB, and CRNM bleeding compared to warfarin patients (Figure). 42,551 (62.6%) were aged 65–79 years and 25,424 (37.4%) were aged ≥80 years. Among apixaban or warfarin patients, those aged 65–79 years had lower Charlson comorbidity index scores (mean 2.7 vs 3.2) and were less likely to have a diagnosis of anemia (34.7–34.9% vs 42.3–42.5%), cerebrovascular disease (14.7–15.7% vs 20.3–20.5%), or dementia (5.0–6.9% vs 20.4–24.6%) compared to patients aged ≥80 years. Across both age subgroups, incidence rates of recurrent VTE, MB and CRNM bleeding were lower for apixaban vs. warfarin. No significant interaction was observed between the treatment and age on recurrent VTE and MB (Figure). There was a significant interaction between treatment and age on CRNM bleeding. Apixaban trended towards a lower risk of CRNM bleeding across both age groups but the treatment effect on CRNM bleeding was larger for patients aged 65–79 years. Conclusion The treatment effects of apixaban vs. warfarin on recurrent VTE and MB were consistently observed across both older age groups in this analysis. More studies are needed to evaluate management of VTE in an older and especially the very elderly population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

Autoimmune disorders and venous thromboembolism: a report from the COMMAND VTE Registry

Abstract Background/Introduction Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a major health problem in the world. Several studies reported that autoimmune disorder is one of important risk factors for development of VTE. Furthermore, autoimmune disorder is thought to be a relatively strong risk factor for VTE recurrence, and extended anticoagulation therapy are recommended for prevention of VTE recurrence in patients with autoimmune disorders. However, it remains controversial whether patients with autoimmune disorders have higher risk for clinical events after VTE than those without. Purpose We sought to evaluate the clinical characteristics, management strategies, and long-term outcomes of patients with autoimmune disorders after excluding patients with active cancer in a large observational database in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE. After excluding patients with active cancer, the current study population consisted of 2332 patients, who were divided into 2 groups: patients with autoimmune disorders and those without. We estimated the cumulative incidences of the clinical outcomes. To adjust for the clinically relevant confounders, we used the multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and their 95% confidence interval (CI) for the risk of patients with autoimmune disorders relative to those without for the clinical outcome measures. Furthermore, we added corticosteroids use at discharge to explore the effect of corticosteroids use. Results There were 188 patients (8.1%) with autoimmune disorders and 2144 patients (92%) without autoimmune disorders. Patients with autoimmune disorders were more often women (74%), and more often received corticosteroids at discharge (69%). The discontinuation rate of anticoagulation therapy was not significantly different between patients with autoimmune disorders and those without (38.0% vs. 39.7% at 3-year, P=0.35). The cumulative 5-year incidences of recurrent VTE and major bleeding were significantly higher in patients with autoimmune disorders than in those without (recurrent VTE: 14.3% vs. 8.3%, P=0.01; major bleeding: 14.9% vs. 8.8%, P=0.02). Even after adjusting confounders of patient characteristic, the excess risk of patients with autoimmune disorders relative to those without remained significant for recurrent VTE (HR 1.81, 95% CI 1.08–2.88, P=0.03) and major bleeding (HR 1.70, 95% CI 1.05–2.63, P=0.03). However, after adjusting for corticosteroids use at discharge, the excess risk was no longer significant for recurrent VTE (HR 1.42, 95% CI 0.75–2.61, P=0.27) nor major bleeding (HR 1.53, 95% CI 0.84–2.69, P=0.16). Conclusions Patients with autoimmune disorders had a higher risk for recurrent VTE and major bleeding than those without, and the excess risk could at least partly be attributable to corticosteroids use. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation