scholarly journals Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism Is Associated with a Significant Decrease in Incidence of Bleeding Compared to Vitamin K Antagonists and Low-Molecular-Weight Heparins

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 978-978
Author(s):  
Ameet Patel ◽  
Hants Williams ◽  
Maria R. Baer ◽  
Ann Butler Zimrin ◽  
Jennie Y Law
Keyword(s):  
Molecular Weight ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Low Molecular Weight ◽  
Inclusion Criteria ◽  
Cell Disease ◽  
Bleeding Events ◽  
Bleeding Rate

Abstract Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD). Several studies confirm that SCD itself is an independent risk factor for development of VTE. However, the optimal pharmacologic anticoagulant remains unknown. Methods: This retrospective single-institution cohort study was exempt by the Institutional Review Board. Data were collected via review of electronic medical records including ambulatory, emergency department, general floor, and intensive care unit encounters. Patients with SCD were identified spanning 1/2009-7/2017 using ICD 9/10 codes. Inclusion criteria were age ≥18 years at time of VTE diagnosis, imaging confirming VTE, and documented compliance based on INR values and/or provider/pharmacy documentation. VTE diagnosis included deep vein thrombosis (DVT) at any location and pulmonary embolism based on documented imaging and ICD 9/10 codes. Anticoagulants included direct oral anticoagulants (DOACs), vitamin K antagonists (VKA), and low-molecular-weight heparin (LMWH). The DOACs used in this study were rivaroxaban, apixaban and dabigatran. Exclusion criteria were known active malignancy, confirmed hypercoagulable risk factors beyond SCD, atrial fibrillation and/or history of major bleeding prior to anticoagulation. Due to low event rates, a log likelihood ratio test of independence was calculated for associations between drug type and two endpoints: bleeding rate and rate of VTE recurrence. Rate of VTE recurrence was defined as a newly diagnosed VTE within 6 months of initiation of anticoagulation. Bleeding rate was defined using International Society on Thrombosis and Hemostasis criteria: bleeding event into a critical site and/or a ≥2 point decrease in baseline hemoglobin. Results: A total of 109 patients with SCD met inclusion criteria. 66 patients (60%) were female. SCD genotypes represented included HbSS in 91 patients (83%), HbSC in 12 (11%) and HbS β+ thalassemia in 4 (4%). There were no patients with HbS-β0 thalassemia. VTEs consisted of 69 DVTs and 43 pulmonary emboli. 31 out of 109 VTEs were provoked, including 30 catheter-related incidents. After initial VTE event, 32 patients received a VKA, 34 received LMWH, and 43 received a DOAC. Within the class of DOACs, 31 patients received rivaroxaban, 5 received apixaban, and 7 received dabigatran. Sixteen of 109 patients (15%) experienced a clinically significant bleeding event, including 8 on VKA, 6 on LMWH, and 2 on a DOAC. Bleeding incidence was least with the DOAC class [0.22 CI (0.04-0.84) p < 0.05], greatest with warfarin [1.55 CI (0.57-4.33) p < 0.05] and slightly less with LMWH [0.64 CI (0.23-1.73) p < 0.05]. There was a significant decrease in incidence of bleeding events in patients receiving a DOAC for anticoagulation, compared to a VKA or LMWH (p = 0.033). At a median follow-up of 11.8 months (range, 3.4 - 60 months), 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH and 13 taking a DOAC (p = 0.833). An association between VTE and SCD genotype could not be identified due to small numbers of patients with non-HbSS genotypes. Conclusion: In patients with SCD and VTE, there was a significant decrease in incidence of bleeding events in patients receiving a DOAC for anticoagulation, compared to a VKA or LMWH (p = 0.033). There was no difference between VTE recurrence rate and choice of initial anticoagulation. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism

2019 ◽  
Vol 142 (4) ◽  
pp. 233-238 ◽  
Author(s):  
Ameet Patel ◽  
Hants Williams ◽  
Maria R.  Baer ◽  
Ann B. Zimrin ◽  
Jennie Y. Law
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Low Molecular Weight ◽  
Cell Disease ◽  
Bleeding Events

Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. Methods: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. Results: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-β+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4–60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). Conclusion: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.

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

2019 ◽  
Vol 26 (2) ◽  
pp. 351-360 ◽  
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.

Low-Molecular-Weight Heparin in Cancer Patients: Overview and Indications

2019 ◽  
Vol 39 (01) ◽  
pp. 067-075 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Anticancer Agents ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

AbstractAlthough venous thromboembolism (VTE) is a well-known cause of death in patients with cancer, both its treatment and prevention remain a challenge in daily practice. Direct oral anticoagulants have emerged as safe and efficacious alternatives to vitamin K antagonists in the general population, and recent clinical trials also support their use in select patients with cancer-associated VTE. Despite this, low-molecular-weight heparins (LMWHs), a comparatively ancient class of antithrombotic drugs, remain the anticoagulants of choice in many indications relevant to modern haematology and oncology. In addition to the treatment of established VTE, these indications include VTE prophylaxis in surgical or acutely ill, hospitalized medical cancer patients as well as the prevention of VTE in high-risk patients undergoing ambulatory chemotherapy. In a constantly changing landscape of approved anticancer agents, this review article summarizes pivotal clinical trial data and guideline recommendations regarding the use of LMWH in haematological and oncological patients, who constitute a highly vulnerable patient population due to their increased risk for both bleeding and VTE recurrence.

scholarly journals Newer Oral Anticoagulants in the Treatment of Acute Portal Vein Thrombosis in Patients with and without Cirrhosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
P. Priyanka ◽  
J. T. Kupec ◽  
M. Krafft ◽  
N. A. Shah ◽  
G. J. Reynolds
Keyword(s):  
Molecular Weight ◽  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Vitamin K ◽  
Low Molecular Weight Heparin ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Vein Thrombosis

Background. Newer oral anticoagulants (NOACs) are being utilized increasingly for the treatment of venous thromboembolism (VTE). NOAC use is the standard of care for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute VTE involving extremities and pulmonary embolism. In contrast, most guidelines in the literature support the treatment of acute portal vein thrombosis (PVT) with low molecular weight heparin (LMWH) and vitamin K antagonists (VKA). Literature evaluating NOAC use in the treatment of acute portal vein thrombosis is sparse. This review focuses on the safety and efficacy of the use of NOACs in the treatment of acute PVT in patients, with or without concomitant cirrhosis, based on the most recent data available in the current literature. Methods. A systematic review was conducted through a series of advanced searches in the following medical databases: PubMed, BioMed Central, Cochrane, and Google Scholar. Keywords utilized were as follows: NOAC, DOAC (direct oral anticoagulants), portal vein thrombosis, rivaroxaban, apixaban, dabigatran, and edoxaban. Articles related to newer anticoagulant use in patients with portal vein thrombosis were included. Results. The adverse events, including bleeding events (major and minor) and the failure of anticoagulation (propagation of thrombus or recurrence of PVT), are similar between the NOACs and traditional anticoagulants for the treatment of acute PVT, irrespective of the presence of cirrhosis. Conclusions. Newer oral anticoagulants are safe and efficacious alternatives to traditional anticoagulation with low molecular weight heparin and vitamin K antagonists in the treatment of acute portal vein thrombosis with or without cirrhosis.

Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants

2017 ◽  
Vol 25 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Ellen M Uppuluri ◽  
Kelly R Burke ◽  
Christina Mactal Haaf ◽  
Nancy L Shapiro
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Relationship Of

Background Direct oral anticoagulants (DOACs) are not recommended for venous thromboembolism (VTE) treatment in patients with cancer because their safety and efficacy have not been compared to low molecular weight heparin (LMWH) in large trials. Routine anti-Xa monitoring in cancer patients on LMWH is also not recommended due to limited data correlating anti-Xa levels and outcomes. Objective Compare the safety and efficacy of DOACs to LMWH and warfarin and assess the relationship of anti-Xa monitoring and outcomes in patients with cancer taking LMWH in an urban university setting. Methods This retrospective, cohort study analyzed the recurrence of VTE and number of bleeding events in patients with cancer. Results There were 131 patients included in the analysis. There was no difference seen in the rate of recurrent VTEs between the LMWH, warfarin and DOAC groups (9.3%, 5.9%, 9.1%, p = 0.89). There was also no difference in the rate of bleeding between groups (10.5%, 14.7%, 9.1%, p = 0.576). There was an increased rate of mortality seen in the LMWH group (26.7% vs. 2.9% vs. 18.2%, p = 0.006). There was no difference seen in recurrent VTE (10.3% vs. 8.5%, p = 0.53) or bleeding (10.3% vs. 10.7%, p = 0.661) between the monitored and unmonitored LMWH patients. Conclusion Results of this analysis suggest DOACs may be as safe and effective as LMWH and warfarin for the treatment of VTE in patients with cancer, and there may be no clinical benefit to routine anti-Xa monitoring in patients on LMWH treatment. However, larger studies are needed to confirm these observations.

scholarly journals Bleeding Outcomes of Gastrointestinal Cancer Patients Treated with Direct Oral Anticoagulants Vs. Low Molecular Weight Heparin

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-27
Author(s):  
Dana E Angelini ◽  
Doaa Attia ◽  
Wei Wei ◽  
Mailey L Wilks ◽  
Barbara Tripp ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Research Funding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Bleeding Rate ◽  
Gi Cancer ◽  
Gi Cancers

Introduction: In recent years, direct oral anticoagulants (DOACs) have been adopted as a treatment option for cancer associated thrombosis (CAT). Randomized trials comparing anti-Xa drugs to low molecular weight heparin (LMWH) showed treatment with DOACs conferred less risk of recurrent venous thromboembolism (VTE), but found higher rates of clinically important bleeding, especially in patients with gastrointestinal (GI) malignancies. Given these findings, there is a need for additional data regarding the safety of DOAC use in GI malignancies. Here, we report bleeding events of GI cancer patients treated with anticoagulation in a large centralized CAT clinic. Methods: We evaluated a prospective cohort of patients referred to our CAT clinic from 8/2014-10/2019. Patients with primary gastrointestinal malignancies treated with therapeutic anticoagulation with LMWH or a DOAC for acute VTE were included. Bleeding was defined using the ISTH criteria for major and clinically relevant non-major bleeding (CRNMB). Bleeding rates were compared between luminal [anus/anal, colon, esophagus, rectal, stomach] and extraluminal GI cancers [gallbladder, liver/bile duct, and pancreas]. Patient characteristics associated with bleeding were evaluated with Fisher's exact test and the association of age with bleeding was analyzed by Wilcoxan rank sum test. Results: Of 463 patients with acute VTE, 73 patients (15.8%) with primary GI tumors were included in the analysis. Males comprised 57.5% of the population, median age was 62 (range 36-86), and 61.6% had stage 4 disease. Figure 1 shows a breakdown of tumor types. Enoxaparin was the most commonly used anticoagulant (n=48, 65.8%), followed by DOAC (n=25, 34.2%). Overall, 16 (21.9%) patients had a bleeding event within 6 months of treatment (7 major bleeds and 9 CRNMB). There was no difference in 6-month bleeding rate between patients treated with LMWH (n= 9, 18.8%) vs. DOAC (n=7, 28.0%), p=0.39. None of the clinical factors analyzed were significantly associated with bleeding (Table 1). There was no difference in bleeding rate in patients with luminal GI cancers vs. extraluminal GI cancers and no difference was found in a three-way association between site, treatment, and bleeding, p=0.40 (Table 2). Conclusions: In our centralized cancer thrombosis clinic, patients with GI malignancies had similar rates of major and CRNMB when treated with LMWH or DOAC. In both cohorts, bleeding rates were high within 6 months of starting anticoagulation. There were no statistically significant differences in bleeding rates based on several clinical characteristics evaluated in this study. Although limited by a small patient population, this study adds to the knowledge of treating GI malignancies with DOACs. There is a need for further prospective evaluations regarding the safety of DOAC use in GI cancer patients and there remains an unmet need for antithrombotic treatments that do not increase bleeding potential. Disclosures McCrae: Novartis: Honoraria; Momenta Pharmaceuticals: Consultancy; Rigel: Consultancy; Dova: Consultancy. Khorana:Bayer: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Merck: Research Funding; Leap: Research Funding; BMS: Honoraria, Research Funding; Seattle Genetics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Janssen: Honoraria.

scholarly journals DOACs- balance between thrombosis and bleeding - A Review

2020 ◽  
Vol 12 (2) ◽  
pp. 32-36
Author(s):  
Emilija Lazarova Trajkovska
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Common Side Effect ◽  
Clotting Factors ◽  
Bleeding Events ◽  
Real World Data ◽  
Reversal Agents ◽  
Life Threatening

Bleeding is a common side effect of anticoagulant use. However, the majority of bleeding events are not life-threatening and can be managed conservatively. The first step in managing any significant bleeding event is to temporarily stop using the anticoagulant. The aim of this review was to determine the appropriate management strategy for an acutely bleeding patient on DOACs.  Direct oral anticoagulants (DOACs) are now widely used in treatment of venous thromboembolism (VTE) and are recommended first-line over vitamin K antagonists (VKAs) in non-cancer associated VTE. Until recently, supportive measures and infusion of clotting factors were the only available options for reversal of DOACs. Within the last 4 years, approval of specific antidotes has led to hopes for improved outcomes in DOAC-related acute bleeding, however limitations remain including cost, availability and "real-world" data. In severe and life-threatening bleeding events, use of non-specific (e.g. PCC) or specific (e.g. idarucizumab, andexanet alpha) reversal agents are recommended. However, further data is needed to compare outcomes between these two management strategies and identify the cost-effectiveness of these various strategies.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p &lt; 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p &gt; 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

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