Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment

Attempts at identifying patients with an elevated risk of bleeding while on anticoagulation following acute venous thromboembolism (VTE) have largely been unsuccessful thus far. We sought to develop a clinical prediction score for bleeding during stable anticoagulation treatment after acute VTE.We performed a post hoc analysis of the pooled RE-COVER studies, two double-blind randomised “sister” trials evaluating dabigatran versus standard treatment in 5107 VTE patients.A score was derived from patients randomised to dabigatran using logistic regression analysis covering the complete follow-up period. The final model, named VTE-BLEED, included six variables and yielded a c-statistic of 0.72 (95% CI 0.67–0.76). Patients from the derivation cohort in the low-risk group (<2 points; 74% of the derivation population) had a bleeding incidence of 2.8% compared to 12.6% in the elevated-risk group (OR 5.0; 95% CI 3.5–7.1). The score proved accurate for our primary end-point, i.e. prediction of major bleeding after day 30 (“stable” anticoagulation), both in patients on dabigatran (c-statistic 0.75, 95% CI 0.61–0.89) and those on warfarin (0.78, 95% CI 0.68–0.86; p=0.77 for difference).The new VTE-BLEED score accurately predicted major bleeding events in VTE patients on stable anticoagulation with both dabigatran and warfarin.

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Characteristics and Outcomes in Patients with Venous Thromboembolism Taking Concomitant Anti-Platelet Agents and Anticoagulants in the AMPLIFY Trial

Thrombosis and Haemostasis ◽

10.1055/s-0038-1676983 ◽

2019 ◽

Vol 119 (03) ◽

pp. 461-466 ◽

Cited By ~ 4

Author(s):

Alexander Cohen ◽

Giancarlo Agnelli ◽

Harry Buller ◽

Alexander Gallus ◽

Gary Raskob ◽

...

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Conventional Therapy ◽

International Normalized Ratio ◽

P Value ◽

Double Blind ◽

Safety Outcome ◽

Anti Platelet Therapy ◽

Efficacy Outcome ◽

Acute Venous Thromboembolism

AbstractThe double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0–3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676; enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%]; enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58–2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52–1.13); interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11–0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15–0.63); interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.

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Risk of major bleeding in patients with venous thromboembolism treated with rivaroxaban or with heparin and vitamin K antagonists

Thrombosis and Haemostasis ◽

10.1160/th15-06-0474 ◽

2016 ◽

Vol 115 (02) ◽

pp. 424-432 ◽

Cited By ~ 25

Author(s):

Walter Ageno ◽

Anne W. S. Rutjes ◽

Akos F. Pap ◽

Harry R. Büller ◽

Marcello Di Nisio

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

The Novel ◽

Anticoagulant Treatment ◽

Bleeding Events ◽

C Statistic ◽

Major Bleeding Events

SummaryThe study aim was to identify predictive factors for major bleeding in patients receiving the novel oral factor Xa inhibitor rivaroxaban or enoxaparin-vitamin K antagonists (VKAs) for the treatment of acute symptomatic venous thromboembolism. We analysed data from patients included in the phase III EINSTEIN DVT and EINSTEIN PE studies. Factors associated with major bleeding events were assessed with best subset variable selection using Cox proportional hazards regression model. Three time windows were considered, i. e. the initial three weeks, after the third week onwards, and the entire duration of the anticoagulant treatment. Model discrimination was estimated using the C-statistic and validated internally by bootstrap techniques. Major bleeding occurred in 40 (1.0 %) of 4130 patients receiving rivaroxaban and in 72 (1.7 %) of 4116 receiving enoxaparin/VKAs, with 44 % of the major bleeding events occurring in the first three weeks of treatment. Significant risk factors for major bleeding were older age, black race, low haemoglobin concentrations, active cancer, and antiplatelet or non-steroidal anti-inflammatory drug therapy. The discrimination of the model for major bleeding was high for the first three weeks (C-statistic 0.73), from the fourth week onwards (C-statistic 0.68), and the entire period of anticoagulant treatment (C-statistic 0.74). This analysis identified risk factors for major bleeding in patients receiving the novel oral anticoagulant rivaroxaban or enoxaparin/VKAs for the treatment of acute venous thromboembolism. The prognostic model based on the combination of identified risk factors may be informative to estimate the risk of major bleeding both during the initial and later phases of anticoagulation.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry

Thrombosis and Haemostasis ◽

10.1160/th08-03-0193 ◽

2008 ◽

Vol 100 (07) ◽

pp. 26-31 ◽

Cited By ~ 268

Author(s):

Nuria Ruíz-Giménez ◽

Carmen Suárez ◽

Rocío González ◽

José Nieto ◽

José Todolí ◽

...

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Low Risk ◽

Ratio Test ◽

Validation Sample ◽

Bleeding Events ◽

Increased Risk ◽

Acute Venous Thromboembolism

SummaryA score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1–0.6), 2.6% (95% CI: 2.3–2.9), and 7.3% (95% CI: 5.6–9.3), respectively. The likelihood ratio test was:0.14 (95% CI:0.07–0.27) for patients at low risk;2.96 (95% CI:2.18–4.02) for those at high risk. In the validation sample the incidence of major bleeding was:0.1%,2.8%,and 6.2%,respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.

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Fondaparinux Combined with Intermittent Pneumatic Compression (IPC) Versus IPC Alone in the Prevention of Venous Thromboembolism after Major Abdominal Surgery: The Randomized APOLLO Study.

Blood ◽

10.1182/blood.v106.11.279.279 ◽

2005 ◽

Vol 106 (11) ◽

pp. 279-279 ◽

Cited By ~ 3

Author(s):

Alexander G.G. Turpie ◽

Kenneth A. Bauer ◽

Joseph A. Caprini ◽

Philip P. Comp ◽

Michael Gent ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Abdominal Surgery ◽

Major Bleeding ◽

Intermittent Pneumatic Compression ◽

Major Abdominal Surgery ◽

Bleeding Events ◽

Double Blind ◽

Vein Thrombosis ◽

Deep Vein

Abstract Background: The selective factor Xa inhibitor fondaparinux has been shown to be at least as effective and as safe as the low-molecular-weight heparin dalteparin for venous thromboembolism (VTE) prevention after major abdominal surgery (Agnelli GA, et al. Br J Surg, 2005, In press). The benefit of fondaparinux in addition to intermittent pneumatic compression (IPC) in VTE prevention after abdominal surgery has not been evaluated. Objective: We performed a randomized, double-blind, placebo-controlled, superiority trial to compare the efficacy and safety of fondaparinux in conjunction with IPC versus IPC alone in patients undergoing major abdominal surgery. Methods: Patients aged at least 40 years undergoing abdominal surgery of at least 45 minutes were included. Patients at highest risk of VTE, requiring pharmacologic prophylaxis in addition to IPC were excluded at the investigator’s discretion. Patients were randomized to receive either fondaparinux 2.5 mg or placebo once daily subcutaneously for 5 to 9 days, starting 6 to 8 hours postoperatively. All patients received IPC. The primary efficacy outcome was the composite of deep-vein thrombosis detected by mandatory bilateral venography, or documented symptomatic deep-vein thrombosis or pulmonary embolism up to day 10. The main safety outcome was major bleeding during the treatment period. A blinded independent committee adjudicated all these outcomes. Follow-up lasted 32 days. Results: Of the 1309 patients randomized between November 2001 and October 2004 (fondaparinux+IPC, n=650; placebo+IPC, n=659), 842 (64.3%) were evaluable for efficacy. The treatment groups were comparable with regard to VTE risk factors, demographic and surgical characteristics; 82% had at least one VTE risk factor (over and above being at least 40 years old and undergoing abdominal surgery). Fondaparinux significantly reduced the VTE rate from 5.3% (22/418) with placebo to 1.7% (7/424), an odds ratio reduction of 69.8% (95% CI: 27.9 to 87.3; p=0.004). Similarly, fondaparinux significantly reduced the proximal deep-vein thrombosis rate from 1.7% (7/417) to 0.2% (1/423; p=0.037). Major bleeding occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux- and placebo-treated patients, respectively (p=0.006). None of the bleeding events were fatal or involved a critical organ. Conclusions: Fondaparinux combined with IPC was significantly more effective than IPC alone for VTE prevention after major abdominal surgery. Although the bleeding risk was increased with fondaparinux compared with placebo, this risk was low and consistent with that observed in previous fondaparinux studies in surgical patients.

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Dabigatran versus Warfarin for Acute Venous Thromboembolism in Elderly or Impaired Renal Function Patients: Pooled Analysis of RE-COVER and RE-COVER II

Thrombosis and Haemostasis ◽

10.1160/th17-03-0176 ◽

2017 ◽

Vol 117 (11) ◽

pp. 2045-2052 ◽

Cited By ~ 16

Author(s):

Samuel Goldhaber ◽

Sam Schulman ◽

Henry Eriksson ◽

Martin Feuring ◽

Mandy Fraessdorf ◽

...

Keyword(s):

Renal Function ◽

Venous Thromboembolism ◽

Elderly Patients ◽

Major Bleeding ◽

Normal Renal Function ◽

Bleeding Risk ◽

Apparent Difference ◽

Bleeding Events ◽

Major Bleeding Events ◽

Acute Venous Thromboembolism

AbstractManagement of acute venous thromboembolism (VTE) with anticoagulants in elderly patients and those with chronic kidney disease poses special challenges. The RE-COVER and RE-COVER II trials showed that dabigatran 150 mg twice daily was as effective as warfarin over 6 months in preventing recurrent VTE, with a lower bleeding risk. We now assess the effects of old age and renal impairment (RI) on pooled trial outcomes in 5,107 patients: 4,504 aged <75 years and 603 aged ≥75 years. The primary efficacy outcome was symptomatic VTE/VTE-related death. Safety outcomes were centrally adjudicated major bleeding events (MBEs), MBEs or clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeds. Baseline renal function was categorized as normal, mild RI or moderate RI. A total of 3,698 had normal renal function and 1,100 and 237 had mild and moderate RI, respectively (23 patients with severe RI and 49 with missing creatinine clearance data were not included). For dabigatran, VTE/VTE-related death decreased from 3.1% (normal renal function) to 1.9% for mild RI and to 0.0% for moderate RI. For warfarin, the event rates were 2.6, 1.6 and 4.1%, respectively. Overall, major bleeding increased with increasing RI (p = 0.0037) and with age (p = 0.4350), with no apparent difference between the dabigatran and warfarin patients. Dabigatran shows better efficacy than warfarin in RI and in the elderly patients, probably because of an increase in the concentration of dabigatran. However, bleeding risk increases with both dabigatran and warfarin in the presence of RI.

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Predicting recurrences or major bleeding in cancer patients with venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th08-02-0125 ◽

2008 ◽

Vol 100 (09) ◽

pp. 435-439 ◽

Cited By ~ 105

Author(s):

Javier Trujillo-Santos ◽

José Nieto ◽

Gregorio Tiberio ◽

Andrea Piccioli ◽

Pierpaolo Micco ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Major Bleeding ◽

Bleeding Complications ◽

Vein Thrombosis ◽

Recurrent Pulmonary Embolism ◽

Acute Venous Thromboembolism ◽

Deep Vein

SummaryCancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3, 805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9–4.9), with PE at entry (OR: 1.9; 95% CI: 1.2–3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2–3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0–2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5–3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2–2.7), metastases (OR: 1.6; 95% CI: 1.1–2.3), recent bleeding (OR: 2.4; 95% CI: 1.1–5.1), or with creatinine clearance <30 ml/ min (OR: 2.2; 95% CI: 1.5–3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.

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Predicting the Risk of Recurrent Venous Thromboembolism: Current Challenges and Future Opportunities

Journal of Clinical Medicine ◽

10.3390/jcm9051582 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1582 ◽

Cited By ~ 1

Author(s):

Hannah Stevens ◽

Karlheinz Peter ◽

Huyen Tran ◽

James McFadyen

Keyword(s):

Venous Thromboembolism ◽

Prediction Models ◽

Clinical Prediction ◽

Bleeding Events ◽

Clinical Prediction Models ◽

Disease Pathogenesis ◽

Recurrent Venous Thromboembolism ◽

Novel Biomarkers ◽

Recurrent Vte ◽

Acute Venous Thromboembolism

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field.

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Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol

Systematic Reviews ◽

10.1186/s13643-019-1175-5 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Faizan Khan ◽

Miriam Kimpton ◽

Tobias Tritschler ◽

Grégoire Le Gal ◽

Brian Hutton ◽

...

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Meta Analysis ◽

Controlled Trials ◽

Bleeding Events ◽

Major Bleeding Events

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

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Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study

European Heart Journal - Quality of Care and Clinical Outcomes ◽

10.1093/ehjqcco/qcz035 ◽

2019 ◽

Vol 6 (2) ◽

pp. 130-137

Author(s):

Nina Gustafsson ◽

Peter Bo Poulsen ◽

Sandra Elkjær Stallknecht ◽

Lars Dybro ◽

Søren Paaske Johnsen

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Home Care Services ◽

Care Hospital ◽

Bleeding Events ◽

Societal Costs ◽

Vein Thrombosis ◽

Primary Care Hospital ◽

Major Bleeding Events ◽

The Impact

Abstract Aims Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. Methods and results Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the ‘difference-in-actual-cost’ method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. Conclusion The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

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Safety and efficacy of direct oral anticoagulants for venous thromboembolism and stroke prophylaxis in patients with hematologic malignancies

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219848810 ◽

2019 ◽

Vol 26 (2) ◽

pp. 351-360 ◽

Cited By ~ 2

Author(s):

Stephanie Kim ◽

Jennifer Namba ◽

Aaron M Goodman ◽

Thi Nguyen ◽

Ila M Saunders

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Hematologic Malignancies ◽

Low Molecular Weight ◽

Direct Oral Anticoagulant ◽

Low Molecular Weight Heparins ◽

Bleeding Events

Purpose Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. Methods This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. Results A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. Conclusion Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

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