scholarly journals Is Anaemia Another Bleeding Risk in Cancer-Associated-Thrombosis?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Nicolas Janus
Keyword(s):  
Red Blood Cells ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Blood Cells ◽  
Research Funding ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Definition Of ◽  
Cancer Associated Thrombosis ◽  
The Impact

INTRODUCTION AND AIMS: Anaemia is very common in cancer patients. However, the impact of anaemia in venous thromboembolic (VTE) patients on the risk of bleeding is not well-known. Consequently, the question of the impact of anaemia in cancer-associated-thrombosis (CAT) patients is important. METHODS: All the literature (PubMed) was reviewed about the potential links between cancer, CAT and anaemia. However, there were no dedicated studies on this topic. Furthermore, the WHO definition of anaemia was the one used in most of the publications RESULTS: Several studies investigated about all the risks of bleeding/VTE in atrial fibrillation and VTE patients, including anaemia. Most of them reported that anaemia exposed VTE patients to a higher risk of bleeding. The COMMANDER study, evaluated the influence of anaemia in VTE patients and reported that VTE patients with mild and moderate/severe anaemia had higher risk for major bleeding and that the risk for major bleeding increased according to the severity of anaemia. The RIETE (Registro Informatizado Enfermedad Tromboembólica) reported that anaemia was found in 57% of the patients with cancer and in 28% without cancer (odds ratio 3.46; 95% CI 3.33-3.60), exposing to a higher risk of major bleeding. The same registry reported also that in CAT patients, anaemia had a two-fold higher rate of major bleeding and fatal bleeding than CAT patients without anaemia. This link between anaemia and bleeding in cancer patients are multifactorial. Indeed, there are both quantitative and qualitative changes in red blood cells that could affect bleeding and thrombosis, as well as interactions of red blood cells with cellular and molecular components of the haemostatic system. Indeed, for example, low haematocrits are associated with bleeding. Finally, it is interesting to notice that there is a gap between the definition of anemia in CAT patients when compared to not CAT cancer patients. Indeed, WHO definition is quite common in VTE and CAT patients but EORTC/NCCN are used in cancer patients for several reasons. As a consequence, it could be important to align on this point. CONCLUSIONS: Anaemia, cancer and thrombosis are closely linked. It is important to screen and manage both anaemia in CAT patients because of the increased risk of bleeding. Consequently, it is important to consider this bleeding risk in CAT patients before initiating an anticoagulants treatment or prophylaxis in cancer patients. Disclosures Janus: Bayer:Honoraria, Research Funding;Pierre Fabre Oncology:Research Funding;Novartis:Honoraria;Gilead:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;B-Braun:Honoraria;Guerbet:Research Funding;TEVA:Research Funding;IPSEN:Honoraria;Pfizer:Consultancy, Honoraria;Roche:Honoraria, Research Funding;Daichii-Sankyo:Honoraria, Research Funding;LEO Pharma A/S:Current Employment, Honoraria.

A Pilot Study in Cancer Patients with Central Venous Catheter Associated Deep Vein Thrombosis in Upper Extremity Treated with Rivaroxaban (Catheter 2)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 878-878 ◽  
Author(s):  
Gwynivere A Davies ◽  
Alejandro Lazo-Langner ◽  
Esteban Gandara ◽  
Vicky Tagalakis ◽  
Martha L Louzada ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Venous Catheter ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Catheter Survival ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Deep Vein

Abstract Introduction Upper extremity deep vein thrombosis (UEDVT) represents up to 10% of cases of venous thromboembolism (VTE) and is frequently associated with central venous catheter (CVC) placement in patients receiving chemotherapy for cancer. UEDVT may be treated with low molecular weight heparin (LMWH) either as monotherapy or subsequently transitioned to warfarin as we have previously shown (Kovacs 2007). Whereas for non-cancer VTE rivaroxaban is at least as efficacious and safe as warfarin, the latter is problematic in cancer patients and direct oral anticoagulants (DOACs) such as rivaroxaban have not been studied to date in this setting. In this study weevaluated thesafety and efficacy of rivaroxaban in the treatment of UEDVT secondary to CVC in patients with cancer. Methods We conducted a multicentre prospective cohort study at 3 centres in Canada between December 2012 and January 2016. We enrolled patients ≥18 years of age with active malignancy and symptomatic proximal UEDVT (axillary or more proximal) with or without pulmonary embolism (PE), associated with a CVC. Exclusion criteria included dialysis catheters, active bleeding, platelet count <75 x 109/L, creatinine clearance <30 mL/min, other anticoagulants, PE with hemodynamic instability, inability to infuse through the catheter after a trial of intraluminal thrombolytic therapy (tissue plasminogen activator,tPa), patients with acute leukemia, patients with multiple myeloma awaiting bone marrow transplant within 3 months, thrombosis involving the brachial,basilic or cephalic veins only, treatment for >7 days with other anticoagulant, need for dual antiplatelet therapy (recent stent), or concomitant use of P-glycoprotein and CYP3A4 inhibitors. Primary objective was an estimate of the proportion of catheter survival at 3 months, defined as infusion failure that does not respond to 2 mg oftPa. Secondary objectives included recurrence of DVT, PE, major bleeding, clinically relevant non-major bleeding (CRNMB) and death. All events were independently adjudicated. Patients were treated with rivaroxaban at a dose of 15 mgpo bid for 3 weeks, followed by 20 mgpo daily for 9 more weeks (minimum 12 weeks).tPa (oralteplase) for management of blocked lines was allowed. Patients were followed clinically for 12 weeks to assess for clinical events including recurrent DVT and/or PE, major bleeding and CRNMB, and by phone at 6 months. Results We included 70 patients (47[67%] women) with a mean age of 54.1 years. DVTs were diagnosed by ultrasound in 68 (97%) patients, and most commonly involved the subclavian (n=55, 79%) and axillary (n=49, 70%) veins, followed by the internal jugular, brachial, brachiocephalic and external jugular veins. Peripherally inserted central catheters (PICC) were most common (n=54, 77%), followed by port-a-cathlines (n=16, 23%). Types of active malignancy included breast (n=29, 41%), colon (n=8, 11%), colorectal (n=5, 7%), rectal (n=3, 4%), prostate (n=1, 1%), and other (n=24, 34%). Catheter survival was 58.6% (95% CI 46.9 to 69.4) at 12 weeks and no catheters were removed due to thrombosis. Patients had their CVCs removed prior to the end of the study due to end of therapeutic need (n=20), infection (n=2), bleeding (n=2), kinking (n=2), patient preference (n=2), and death (n=1). The 3-month incidence rate of recurrent VTE was 1.43% (95% CI 0.25 to 7.66). There was 1 episode of recurrent VTE presenting as a fatal PE at 6 weeks. It was not known if the patient had a concurrent leg DVT at the time of the PE. There were no other deaths from any cause during the study. There were 11 bleeding events in 9 patients (12.85%, 95%CI 6.9 to 22.7), 6 major and 5 CRNMB (Figure 1). All bleeding events happened during the first 39 days of treatment. 7 patients discontinued anticoagulation during the study due to death (n=1), patient or clinician preference (n=5) and dermatological adverse reaction (n=1). Discussion In this study rivaroxaban showed promise in treating CVC-associated UEDVT in cancer patients, resulting in preserved CVC function. However, the bleeding rates and the occurrence of 1 death due to pulmonary embolism is concerning since we cannot exclude a causative role for the known UEDVT. Further studies are still required prior to recommending rivaroxaban in this setting. Figure 1 Kaplan-Meier curve for cumulative bleeding risk. Figure 1. Kaplan-Meier curve for cumulative bleeding risk. Disclosures Lazo-Langner: Daiichi Sankyo: Research Funding; Bayer: Honoraria; Pfizer: Honoraria. Tagalakis:Bayer: Honoraria. Louzada:Celgene: Consultancy, Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Janssen: Consultancy, Honoraria. Kovacs:Bayer: Honoraria, Research Funding; Daiichi Sankyo Pharma: Research Funding; LEO Pharma: Honoraria; Pfizer: Honoraria, Research Funding.

scholarly journals Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
Doaa Attia ◽  
Xuefei Jia ◽  
Mailey L Wilks ◽  
Barbara Tripp ◽  
Christopher D'Andrea ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Cleveland Clinic ◽  
Treatment Groups ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P&gt;0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

scholarly journals Safe and Effective Use of Rivaroxaban for Treatment of Cancer-Associated Venous Thromboembolic Disease: A Quality Improvement Initiative

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 431-431 ◽  
Author(s):  
Simon Mantha ◽  
Yimei Miao ◽  
Debra Sarasohn ◽  
Jonathan Kessler ◽  
Rekha Parameswaran ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Pathway ◽  
Bleeding Risk ◽  
Event Type ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis ◽  
Low Rate

Abstract Background: Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. LMWH injections are painful and costly. Rivaroxaban, an oral direct factor Xa inhibitor, was FDA approved in 2012 for treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but there has been a knowledge gap for its use in patients with cancer-associated thrombosis (CAT). Under a Quality Assurance Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT, and began to offer rivaroxaban as an alternative to enoxaparin, in January 2014, for patients who met appropriate clinical criteria. We are tracking all cancer patients with PE or symptomatic proximal DVT, whose full course of anticoagulation is with rivaroxaban (allowing up to 3 days of initial parenteral anticoagulation). We now report the characteristics of the first 200 patients, and an outcome analysis of our first 100 patients, who have been treated for at least 6 months or otherwise reached an endpoint. Materials and Methods: The Clinical Pathway guidelines will be available on request, pending publication. Patients were not treated with rivaroxaban if they had active gastrointestinal or genitourinary lesions, or had undergone gastric resection due to anticipated excess bleeding risk or reduced absorption. This excluded under 5% of patients. The Pathway provided dosing guidelines in the setting of thrombocytopenia, advanced age, transient renal, or hepatic dysfunction. Primary endpoints include new or recurrent PE, symptomatic proximal lower extremity DVT, major bleeding (ISTH definition), clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. Considering those outcomes as competing risks, the cumulative incidence of each event type was calculated using R 3.2.0 for Windows and package "Survival". Results: The characteristics of our first 200 patients are in Table 1. 70% of the patients had PE. Of the solid tumor patients, 65.6% had metastatic disease. The first 100 patients have completed at least 6 months of rivaroxaban anticoagulation or otherwise reached a primary endpoint. At 6 months, the cumulative incidence of death was 14.4% (95% CI=6.8-21.4%), new or recurrent VTE was 4.3% (95% CI=0.1-8.4%), major bleeding was 1.1% (95% CI=0-3.1%), and clinically relevant non-major bleeding leading to rivaroxaban discontinuation was 7.9% (95% CI=2.1-13.3%). Conclusions: In the analysis of the first 100 patients entered into our QAI program, the rates of major bleeding, and new or recurrent VTE compare favorably to two published studies of LMWH for treatment of cancer associated thrombosis. In the CLOT study (Lee et al, NEJM, 2003) and the Daltecan study (Francis et al, JTH, 2015), the 6-month rates of new or recurrent VTE were approximately 9%, and the rates of major bleeding were 6% and 9.5% respectively. Our final analysis awaits the completion of 6 months follow-up on 200 patients, to be completed in December 2015. But the rates of major bleeding and recurrent VTE at this point suggest safety and efficacy to be at least non-inferior to LMWH, with the advantage of reduced patient burden, and support the ongoing use of our Clinical Pathway. Our low rate of major bleeding likely is influenced by the exclusion of patients with active GI or GU lesions, who would be expected to have a high bleeding risk with an oral direct anticoagulant. However, we estimate this excluded less than 5% of cancer patients with VTE. Further, we anticipated reduced drug clearance in the elderly, and used a reduced dose for patients greater than 75 years of age. This appeared to be associated with no loss in efficacy, and helped maintain a low rate of major bleeding. A randomized trial is the optimal approach to establish non-inferiority or superiority of rivaroxaban to LMWH for cancer associated thrombosis. However, our QAI Clinical Pathway provides guidance and reassurance for rivaroxaban use until a randomized trial is conducted. Table. Baseline Characteristics of Patients Characteristic Number of Individuals Gender Male 82 Female 118 Event Type PE, with or without DVT 140 Proximal, Symptomatic Lower extremity DVT 60 Cancer Type Solid Tumor 186 Hematologic Malignancy 14 Cancer Stage (Of Solid Tumors) No Evidence of Disease (Post-Cancer Surgery) 11 (5.9%) 1 1 (0.5%) 2 4 (2.2%) 3 16 (8.6%) 4 122 (65.6%) Unknown 32 (17.2%) Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identifying Predictors for Bleeding in Hospitalized Cancer Patients: A Cohort Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 529-529
Author(s):  
Rushad Patell ◽  
Alejandra Gutierrez ◽  
Lisa Rybicki ◽  
Alok A. Khorana
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Cohort Study ◽  
Length Of Stay ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Reason For Admission

Abstract Background: Bleeding and thrombosis are both major complications of hospitalization in cancer patients. We have previously shown that rate of inpatient venous thromboembolism (VTE) is 4% in a general oncology population (Patell et al, ASCO 2016). Concern regarding bleeding risk may reduce compliance with thromboprophylaxis. A better understanding of predictors of bleeding could optimize use of prophylaxis but there remain major knowledge gaps regarding risk factors for in-hospital bleeding in cancer patients. We assessed major and clinically relevant bleeding incidence and identified risk factors at admission associated with subsequent in-hospital bleeding risk in a cohort of hospitalized cancer patients. Methods: We conducted a retrospective cohort study of consecutive adults admitted to general oncology floor at Cleveland Clinic from 2013-14 (n= 3466). Patients were excluded for bleeding on admission (108). Data collected included demographics, body mass index (BMI), cancer type, length of stay (LOS), use of anticoagulants and baseline laboratory values (+48 hours). Bleeding was assessed using the ISTH definitions of major bleeding and clinically relevant non-major bleeding [Schulman 2005 and Decosus 2011]. Data were collected using an electronic query system of electronic health records. Reason for admission and all bleeding events were confirmed by manual chart review. Univariate risk factors were identified with logistic regression analysis. Multivariable risk factors were identified with stepwise logistic regression and confirmed with bootstrap analysis. Results are summarized as odds ratio (OR) and 95% confidence interval (CI). Results: The study population comprised 3,358 patients of whom 69 (2.1%) developed major and clinically relevant non-major bleeding during hospitalization. Median age was 62 (range, 19-98) years and 56% were male. Median length of stay (LOS) was 5 (range, 0-152) days. The majority of bleeding events were either gastrointestinal (N=30, 43%) or intracranial (N= 13, 19%). In univariate analysis, luminal gastrointestinal (GI) cancers (OR 4.2, CI 2.4-7.5, P<0.001), anemia as reason for admission (OR 9.1, CI 5.1-16.4, P<0.001), thrombocytopenia (OR 1.6, CI 1.0-2.6, P=0.046), leukocytosis (OR 2.1, CI 1.2-3.7,P=0.005), low hemoglobin (OR 3.2, CI 1.4-7.1 P=0.003), BMI ≥ 40 kg/m2 (OR 2.6, CI 1.1-5.94, P=0.018) and anticoagulant use on admission (OR 0.4, CI 0.3-0.8, P=0.004) were significantly associated with bleeding. In multivariable analysis, anemia as the reason for admission, primary cancer site, BMI>40, thrombocytopenia and low hemoglobin on admission remained predictive of bleeding (table 1). Conclusion: The incidence of major and clinically relevant bleeding in a large population of hospitalized cancer patients was about 2%, compared to incidence of inpatient VTE in a similar population of 4%. Risk factors at admission included type of cancer and morbid obesity. Improved prediction of bleeding risk can assist physicians in optimizing selection of thromboprophylaxis in this population that is also at increased risk of VTE. Disclosures Khorana: Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

scholarly journals Cancer-Associated Thrombosis: Anatomic Distribution of the Index Event Is Not a Reliable Predictor of Recurrence Risk

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1252-1252
Author(s):  
Gerald A. Soff ◽  
Jeanette Batista ◽  
Debra M. M Sarasohn ◽  
Jodi V Mones ◽  
Cy Wilkins ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Vascular Involvement ◽  
Index Event ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis ◽  
The Relationship ◽  
Assessment Initiative ◽  
Calf Vein

Abstract Introduction: Cancer associated thrombosis (CAT) is a common complication of cancer, associated with significant morbidity and mortality. While incidence varies with cancer type, stage, chemotherapy, and other factors, estimates are that up to 20% of cancer patients will experience at least one venous thromboembolic (VTE) episode. VTE consist of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and there is a spectrum of vascular involvement. DVTs are classified as proximal (popliteal vein or above) and PE may be subsegmental, segmental, lobar, main, or saddle embolism. Our standard approach has been to treat all DVTs and all PEs in cancer patients, regardless of the size of the involved vessel. However, it is not clear if the risk of recurrent VTE in a patient with a "small" subsegmental PE, or a calf vein DVT, is comparable to that of an individual with a larger vascular involvement. In this study, we characterized the largest vessel involved in the initial VTE episode, and the relationship with recurrent VTE. Methods: All patients at MSKCC with CAT are monitored within an existing Quality Assessment initiative. From 1/1/2014 through 10/31/2016, 1072 patients with CAT were treated with rivaroxaban (Riva). (The overall outcomes of this cohort are the subject of a separate abstract.) In this study we compared the rate of recurrent VTE in patients with a distal (calf) DVT with proximal DVT, and PE. We designated the most proximal, or largest thrombosed vessel. As patients with a PE do not routinely undergo Doppler leg ultrasound, we are unable to differentiate PE with a DVT from those without. We also analyzed if the PE was unilateral or bilateral. We used competing risk endpoints for the purpose of this analysis, including recurrent VTE, major bleeding, clinically relevant non-major bleeding leading to discontinuation of Riva, and death. Results: In the Table, we present the data on the relationship of the initial VTE and the risk of recurrence. The majority of CAT events (55%) were PE. There were no significant differences in the rates of recurrent VTE between patients with a PE, a distal DVT or proximal DVT. Within patients with a PE as the index VTE event, there was no significant association between the risk of recurrent VTE and the size of the PE. A subsegmental PE as an index event was associated with a comparable rate of recurrent VTE when compared with segmental and more proximal vessel involvement. The only meaningful trend towards a higher rate of recurrent VTE was in patients whose index event was a bilateral PE, compared with unilateral, although this association did not reach statistical significance. Conclusions: The goal of this Quality Assessment initiative was to evaluate the risk of recurrent VTE in cancer patients to determine if distal DVT's or subsegmental PEs had a significantly lower rate of recurrence than other VTE episodes. Our analysis indicated that the risk of recurrent VTE is not related to the size of the index thrombosed vessel. Within PE, from large, proximal index events through to subsegmental PE, the risk of recurrent VTE is comparable. Similarly, there was only a trend towards lower risk of recurrent VTE in patients with an index distal DVT, versus proximal DVT. But this association was not statistically significant, with overlapping 95% confidence intervals. The one parameter that appeared to have the strongest prediction of recurrent VTE was patients with bilateral PE, versus unilateral. However, this too was only a trend, not statistically significant, and was not one of the parameters within our initial hypotheses. We were unable to identify any subgroup of index VTE, based on vessels involved, that had a significantly lower rate of recurrent VTE while on anticoagulation. Within cancer patients, a subsegmental PE or a distal, calf vein DVT are associated with a risk of recurrent VTE comparable to thrombosis of larger vessels. Table Table. Disclosures Soff: Janssen: Research Funding; Amgen: Research Funding. Mantha:Janssen: Research Funding; GLG: Consultancy; Heidell, Pittoni, Murphy & Bach, LLP: Consultancy.

Bleeding Risk in Thrombocytopenic Cancer Patients with Venous Thromboembolism (VTE) Receiving Anticoagulation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3408-3408 ◽  
Author(s):  
Naresh Pemmaraju ◽  
Michael H. Kroll ◽  
Vahid Afshar-Kharghan ◽  
Thein H Oo
Keyword(s):  
Platelet Count ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Platelet Counts ◽  
End Point ◽  
History Of ◽  
The Impact

Abstract Abstract 3408 Introduction: Cancer-associated thromboses are commonly treated with anticoagulants, which sometimes cause bleeding. Cancer patients receiving chemotherapy develop thrombocytopenia and these patients are at an increased risk of bleeding. Because of concerns about bleeding risk when one combines anticoagulation and thrombocytopenia, the National Comprehensive Cancer Network considers a platelet count of less than 50,000/cmm as a contraindication to anticoagulation and the American Society of Clinical Oncology recommends anticoagulation in thrombocytopenic cancer patients with caution. This retrospective chart review aims to evaluate bleeding risks associated with anticoagulation in cancer patients with platelet counts of less than 50,000/cmm. Methods: From Jaunary 2008 to January 2011 chart reviews were made of 2,711 patients (18 years or older) with ICD9 diagnoses emcompassing venous thromboembolism and thrombocytopenia. The following cases were excluded from the study, (1) no anticoagulation, (2) platelet count above 50,000/cmm, (3) tumor thrombus, (4) asynchronous thrombosis and thrombocytopenia, (5) therapeutic embolization, (6) history of thrombotic events, (7) history of thrombocytopenia. The primary end point was bleeding and the secondary end point was recurrent thrombosis. Results: 53 patients were identified; male: female = 1.2 : 1.0, median age 58 (range 19 – 84), hematologic malignancies (including myelodysplasia): solid tumors = 1.8 : 1.0, median stage of cancer = 4.0, median baseline RIETE bleeding risk score = 2.5 (range 1.0 – 5.0), median platelet count at the start of anticoagulation = 33,000/cmm (range 18,000 – 49,000/cmm), median duration of anticoagulation = 83 days (range 4 – 740 days), DVT only = 35 cases, PE only = 13 cases, DVT + PE = 5 cases, unilateral DVT: bilateral DVT = 7 : 1, upper extremity DVT: lower extremity DVT = 1.3 : 1.0. 44 patients were treated with low molecular weight heparin (LMWH), 5 patients were treated with fondaparinux and 4 patients were treated with unfractionated heparin (UFH). 23 patients received anticoagulation for less than 3 months, including 11 patients who received it for < 14 days. 15 patients had ≥ 25% dose reductions of anticoagulants. Overall, 5/53 patients (9.4%) suffered bleeding while receiving anticoagulation. Using the WHO bleeding scale, there was 1 grade 5 bleeding event (cerebral hemorrhage in a patient with AML being treated with UFH infusion for cavernous sinus thrombosis); 1 grade 4 bleeding event (tracheostomy hemorrhage in a patient receiving therapeutic dose fondaparinux) and 3 grade 2 bleeding events (1 epistaxis while on therapeutic enoxaparin 1mg/kg/12 hours, 1 case of oozing from bone marrow biopsy site while on dalteparin 200 IU/kg/day and 1 episode of hematuria while on reduced dose enoxaparin 1mg/kg/day). Overall, there was a 1 recurrent thrombotic episode (1.8%), which occurred in a patient receiving dalteparin 100 IU/kg/day. Conclusion: We conclude that anticoagulation during periods of thrombocytopenia < 50,000/cmm is feasible and may be safe. Major bleeding risk (WHO grades 3, 4 and 5) was 2/53 (3.8%). This is comparable to the 6% major bleeding rate observed with 6 months of standard LMWH anticoagulation in cancer patients with platelet counts above 75,000/cmm, as reported in the CLOT trial (N Engl J Med 2003;349:146–53). Recurrence risk is 1/53 (1.8%). This is less than the 9% six month recurrence rate observed in those treated with LMWH in the CLOT trial. Our data also suggest that the impact of anticoagulation dose-reduction appears to be minor. Validation of our conclusions will require prospective studies, which also would provide a thrust towards optimizing the therapeutic index of anticoagulation therapy in thrombocytopenic cancer patients suffering from VTE. Disclosures: Kroll: Aplagon: Membership on an entity's Board of Directors or advisory committees; Optimer: Consultancy; Leo: Honoraria, Travel Expenses, Travel Expenses Other.

Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tseng ◽  
S Bhatt ◽  
M Girardo ◽  
D Liedl ◽  
P Wennberg ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Triple Therapy ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

The risk of bleeding with warfarin: A systematic review and performance analysis of clinical prediction rules

2007 ◽  
Vol 98 (11) ◽  
pp. 980-987 ◽  
Author(s):  
Karen Dahri ◽  
Peter Loewen
Keyword(s):  
Systematic Review ◽  
Major Bleeding ◽  
Warfarin Therapy ◽  
Risk Index ◽  
Predictive Ability ◽  
Bleeding Risk ◽  
Clinical Prediction ◽  
Clinical Prediction Rules ◽  
Prediction Rules ◽  
Risk Of Bleeding

SummaryIt was the objective of this article to qualitatively review and evaluate the clinical prediction rules (CPRs) available for estimating bleeding risk in patients commencing warfarin therapy. A systematic review of PubMed (1949 to December 2006), MEDLINE (1966 to December 2006); EMBASE (1980 to December 2006), Cochrane Database of Systematic Reviews (to December 2006), and International Pharmaceutical Abstracts (1970 to Demember 2006) was conducted. Seven studies were found that detailed CPRs used to assess risk of bleeding prior to commencing warfarin therapy. Four studies described distinct CPRs. The remaining three studies were further validations of one of the CPRs, the Outpatient Bleeding Risk Index. The Outpatient Bleeding Risk Index was classified as being of Level 2 evidence while the remaining three indices were classified as being of Level 4 evidence. In no case did the CPRs exhibit performance characteristics that would indicate“strong” ability to predict the presence of absence of major bleeding among warfarin recipients. The modified Outpatient Bleeding Risk Index exhibited moderate predictive ability for major bleeding in two studies, although pooling of all studies of this CPR did not reveal moderate or better performance. None of the CPRs identified “any bleeding” with moderate or strong predictive ability. None of the available CPRs exhibit sufficient predictive accuracy or have trials evaluating the impact of their use on patient outcomes. Hence, no existing CPR can be recommended for widespread use in practice at present.

scholarly journals Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study: A Perioperative Management Plan for Patients with Atrial Fibrillation Who Are Receiving a Direct Oral Anticoagulant

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. LBA-5-LBA-5 ◽  
Author(s):  
James Douketis ◽  
Alex C. Spyropoulos ◽  
Joanne M Duncan ◽  
Marc Carrier ◽  
Gregoire Le Gal ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Major Bleeding ◽  
Research Funding ◽  
Perioperative Management ◽  
Elective Surgery ◽  
Bleeding Risk ◽  
Advisory Board ◽  
Advisory Committees ◽  
Arterial Thromboembolism ◽  
High Bleeding Risk

Abstract Introduction: The perioperative management of patients who are taking a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require an elective surgery/procedure is uncertain. No studies have addressed the timing of perioperative DOAC interruption and resumption, and if perioperative heparin bridging and coagulation function testing are needed. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study hypothesized that a simple, standardized perioperative management strategy, based on DOAC-specific interruption and resumption intervals, that foregoes perioperative heparin bridging and coagulation function testing, is safe for patient care, with associated low rates of major bleeding (1%) and arterial thromboembolism (0.5%). We postulated that this management yields a high proportion of patients (>90%) with a minimal to no DOAC level at surgery/procedure. Methods: PAUSE is a prospective study with 3 parallel DOAC cohorts of patients with AF taking apixaban, dabigatran or rivaroxaban and requiring anticoagulant interruption for an elective surgery/procedure. Patients were managed using a standardized protocol based on DOAC pharmacokinetic properties, procedure-associated bleeding risk (Appendix 1) and creatinine clearance (CrCl). DOACs were interrupted for 1 day before and after surgery for a low bleed risk surgery and 2 days before and after a high bleed surgery; longer interruption was done in patients on dabigatran with a CrCl<50 mL/min (Figure 1). A blood sample was obtained just before the procedure to measure residual DOAC levels (Appendix 2). Heparin bridging and preoperative coagulation testing were not used to manage patients. Patient follow-up occurred weekly for 30 days post-procedure for the primary clinical outcomes of major bleeding and arterial thromboembolism (Appendix 3). The incidence (95% confidence interval [CI]) of clinical outcomes was determined for each DOAC cohort using an intention-to-treat (ITT) analysis (interrupted at least 1 DOAC dose) and per-protocol analysis (adhering to DOAC interruption and resumption protocol). Results: We enrolled 3007 patients from 23 sites in Canada, the U.S. and Europe (Appendix 4). The patient characteristics were (Figure 2): mean age 72.5 years; 66.1% male; 33.5% high bleeding risk surgery/procedure, with 1257 patients in the apixaban cohort, 668 in the dabigatran cohort and 1082 in the rivaroxaban cohort (Table 1). DOAC interruption and resumption intervals are shown in Table 2. The 30-day postoperative rate (95% CI) of major bleeding was 1.35% (0-2.00) in the apixaban cohort, 0.90% (0-1.73) in the dabigatran cohort and 1.85% (0-2.65) in the rivaroxaban cohort; the rate (95% CI) of arterial thromboembolism was 0.16% (0-0.48) in the apixaban cohort, 0.6% (0-1.33) in the dabigatran cohort and 0.37% (0-0.82) in the rivaroxaban cohort (Table 3). There were 2541 (84.5%) patients with preoperative DOAC levels measured: a level <50 ng/ml occurred in 90.5% of patients in the apixaban cohort, in 95.1% of the dabigatran cohort and in 96.8% of the rivaroxaban cohort. Of 1007 patients having a high bleeding risk procedure, 832 (82.6%) had DOAC levels measured: 98.8% had a level <50 ng/mL (Table 4). Rates of major bleeding and arterial thromboembolism in the per protocol analysis were comparable to those of the ITT analysis (Table 5). Conclusions: In patients with AF who were taking a DOAC (apixaban, dabigatran, rivaroxaban) and required anticoagulant interruption for an elective surgery/procedure, using a standardized DOAC-specific perioperative management strategy was safe for patient care, with associated low rates of perioperative MB (<2%) and ATE (<1%). Further, a high proportion of patients (>90% overall; 98.8% at high bleeding risk) had a minimal or no residual DOAC level at the time of the surgery/procedure. PAUSE is the largest study, to date, that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care. Study Funding: CIHR (313156) and the H&S Foundation of Canada (G-14-0006136). Aniara-Hyphen Biomed (assays). Acknowledgments: We thank Drs. Walter Ageno, David Garcia, Lehana Thabane, Wendt Lim, Lori Linkins, William Ristevski, and Demetrios J. Sahlas. Also, Kayla Lucier, Grace Wang, Tara McDougall, and HRLMP and CRLB. Supported by CanVector and REDCap. Disclosures Douketis: Bayer: Other: Advisory Board; Janssen: Consultancy; BMS: Other: Advisory Board; Biotie: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Portola: Other: Advisory Board; Pfizer: Other: Advisory Board. Spyropoulos:Janssen Scientific Affairs, LLC: Consultancy. Carrier:Bayer: Honoraria; Leo Pharma: Research Funding; Pfizer: Honoraria; BMS: Honoraria, Research Funding. Vanassche:Bayer: Consultancy; Boehringer Ingelheim: Consultancy; BMS/Pfizer: Consultancy. Verhamme:Bayer: Honoraria, Research Funding; Medtronic: Honoraria; Portola: Honoraria; Boehringer Ingelheim: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Shivakumar:Pfizer: Honoraria; Servier: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria. Gross:Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Servier: Honoraria. Lee:Pfizer: Consultancy, Research Funding; BMS: Research Funding; Servier: Honoraria; LEO Pharma: Consultancy, Research Funding; Bayer: Consultancy, Honoraria. Le Templier:BMS-pfizer: Honoraria. Wu:Leo Pharma: Honoraria; Pfizer: Honoraria; BMS-Pfizer: Honoraria. Coppens:Bayer: Honoraria, Other: Non-financial support, Research Funding; CSL Behring: Honoraria, Other: non-financial support, Research Funding; Uniqure BV: Research Funding. Arnold:Bristol Myers Squibb: Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding. Caprini:Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Recovery Force: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizor: Membership on an entity's Board of Directors or advisory committees; Janssen R&D: Membership on an entity's Board of Directors or advisory committees. Summer:Octapharma: Honoraria. Schulman:Daiichi-Sankyo: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Boehringer-Ingelheim: Honoraria, Research Funding.

scholarly journals Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Major Bleeding ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P&lt;0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p&lt;0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p&lt;0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

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