scholarly journals Benefit and Risk of Primary Thromboprophylaxis in Ambulatory Patients with Advanced Pancreatic Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4266-4266
Author(s):  
Nay Min Tun ◽  
Elizabeth Guevara ◽  
Thein H. Oo
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Risk Difference ◽  
Bleeding Events ◽  
Patients With Cancer ◽  
Ambulatory Patients

Abstract Background: Vascular thromboembolism (VTE) is the second leading cause of death in patients with cancer. Despite the fact that mortality is increased in cancer patients who developed VTE compared to those without VTE, empirical prophylaxis against VTE in ambulatory patients with cancer remains controversial. The risk of VTE is higher for certain types of cancer such as pancreatic and hematologic malignancies, in patients with advanced cancer, and in those who are undergoing chemotherapy or radiotherapy. We carried out a systematic review and meta-analysis of randomized controlled trials (RCT) to investigate the benefit and risk of primary thromboprophylaxis (PTP) with low-molecular weight heparins (LMWH) in ambulatory patients with advanced pancreatic cancer receiving chemotherapy. Methods: We undertook an extensive literature search using MEDLINE and EMBASE databases through July 13, 2014. References of the potential studies were also reviewed for any additional relevant studies. RCTs with reduction in symptomatic VTE as a primary endpoint were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio (RR) as well as the pooled absolute risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied because there was homogeneity among the included studies (I2 = 0.00). Results: Two RCTs and a subgroup of another two RCTs, comprising a total of 738 patients with advanced pancreatic cancer, were eligible for analysis. Antithrombotics used in these trials were nadroparin (prophylactic dose), semuloparin (prophylactic dose), enoxaparin (semi-therapeutic dose), and dalteparin (therapeutic dose). The duration of PTP lasted from three to six months. The crude incidence of VTE was 5.51% and 15.12% in those receiving anticoagulants and in control patients, respectively, with a risk ratio of 0.36 (CI: 0.22 – 0.59, p < 0.0001). The absolute risk difference in VTE was 9.5% (CI: 5.3 – 13.8 %, p < 0.0001), with an estimate of the number needed to treat (NNT) of 10.5 to prevent one symptomatic VTE event. Major bleeding events were reported in 5.48% of patients on thromboprophylaxis compared to 7.94% in control patients according to an analysis of two RCTs. The pooled relative risk for major bleeding was statistically nonsignificant at 0.68 (CI: 0.33 – 1.39, p = 0.29). Conclusions: A previous meta-analysis reported that approximately 60 patients were required to be treated with LMWH to prevent one symptomatic VTE among unselected cancer patients receiving chemotherapy. Our meta-analysis revealed that thromboprophylaxis resulted in a significant reduction in symptomatic VTE events with NNT of 10.5 without an increase in major bleeding events, indicating that PTP with anticoagulants in advanced pancreatic cancer patients receiving chemotherapy may be beneficial. Further large randomized phase III studies are recommended to evaluate the effects of such targeted thromboprophylaxis on morbidity, mortality and the costs of care. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Low Molecular Weight Heparin Thromboprophylaxis in Ambulatory Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 490-490 ◽  
Author(s):  
Nicole M. Kuderer ◽  
Thomas L. Ortel ◽  
Alok A Khorana ◽  
Charles W. Francis ◽  
Gary H. Lyman
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Bleeding Events ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

Abstract Abstract 490 Background: Patients with cancer experience an increased risk of venous thromboembolism (VTE) throughout the course of their illness. The risk of VTE appears to be greatest among hospitalized cancer patients, in the perioperative period of major surgery and in those receiving systemic cancer therapies. While encouraged in hospitalized and surgical patients, routine VTE prophylaxis for cancer patients is not recommended in the ambulatory setting except in very selective high risk circumstances. A number of randomized clinical trials (RCTs) of low molecular weight heparin (LMWH) in ambulatory cancer patients have been reported with inconsistent results. Presented here are the results from our updated meta-analysis of LMWH prophylaxis, including recently presented RCTs. Methods: A systematic review of RCTs of VTE prophylaxis with LMWH in ambulatory cancer patients was conducted including the results of published and recently presented trials. Electronic databases including Medline, EMBASE, and Cochrane Library were searched along with meeting abstracts from ASCO and ASH. Eligibility criteria included RCTs of ambulatory cancer patients randomized to LMWH or not and reporting rates of VTE as a primary outcome (primary VTE prophylaxis studies) or a secondary outcome. Dual blinded data extraction was performed with conflict resolution by a third party. Following assessment of heterogeneity, meta-analyses using the method of Mantel and Haenszel were conducted providing weighted summary estimates of both relative risk (RR) and absolute risk (AR) ± 95% confidence intervals (95% CI). Primary study outcomes consist of all reported VTE events and all major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: A total of 7 RCTs of LMWH in ambulatory patients with cancer were identified with a total of 2,960 patients including 1,685 receiving LMWH and 1,275 controls. These include 3 RCTs with various solid tumors and one RCT each in breast cancer, lung cancer, pancreatic cancer, and glioblastoma. Patients receiving LMWH experienced 47 VTE events compared to 74 control subjects for crude rates of 2.79% and 5.80%, respectively. No significant heterogeneity was observed across trials (Cochran Q=6.19; I2=3.03; P=.40). The RR for VTE across trials was estimated at 0.54 [95% CI: 0.38 – 0.78; P=.001] while the AR decrease was 2.55% [95% CI: 1.06% – 4.05%; P<.001]. The RR for VTE for the 5 primary VTE prophylaxis trials was 0.50 [95% CI: 0.34 – 0.75; P<.001] with an AR decrease estimated at 2.95% [95% CI: 1.26 – 4.63%; P<.001]. Major bleeding events were reported in 30 patients receiving LMWH compared to 15 control subjects for crude rates of 1.78% and 1.18%, respectively. No significant heterogeneity was observed across trials (Cochran Q=5.50; I2=0.0; P=.481). The RR for major bleeding across trials was estimated at 1.74 [95% CI: 0.95 – 3.18; P=.071], while the AR increase was 0.75% [95% CI: 0.17% – 1.33%; P=.011]. The RR for major bleeding in the 5 primary prophylaxis trials was 2.27 [95% CI: 1.12 – 4.59; P=.022] with AR increase estimated at 1.27% [95% CI: 0.27% – 2.27%; P=.013]. Conclusions: LMWH thromboprophylaxis in ambulatory cancer patients is effective and results in a significant 46% relative risk reduction of venous thromboembolism. However, the risk of VTE is low in this setting and the absolute risk reduction with prophylactic anticoagulation is only 2.6%, while concerns remain about the increase in major bleeding events. Additional research is needed to identify ambulatory cancer patients at increased risk for VTE, in whom VTE prophylaxis may have a more favorable risk-benefit ratio. Disclosures: Ortel: Eisai: Research Funding. Khorana:sanofi-aventis: Consultancy; Eisai: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding. Francis:Eisai: Consultancy, Honoraria.

Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer

2021 ◽  
Author(s):  
Giancarlo Agnelli ◽  
Andrés Muñoz ◽  
Laura Franco ◽  
Isabelle Mahé ◽  
Benjamin Brenner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Gastrointestinal Cancer ◽  
Absolute Risk ◽  
Gynecological Cancer ◽  
Risk Difference ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Genitourinary Cancer ◽  
Spectrum Of Patients

AbstractEfficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.5%), lung in 200 (17.3%), breast in 155 (13.4%), genitourinary sites in 139 (12%), gynecological sites in 119 (10.3%), and was hematological in 85 patients (7.4%). Rates of VTE recurrence were 10.9% in patients with gynecological, 8.8% with gastrointestinal, 6.5% with genitourinary, and 5.5% with lung cancer with lower rates in the other sites of cancer. Rates of major bleeding were 7.2% in patients with genitourinary and 4.8% with gastrointestinal cancer, with lower rates in patients with other sites of cancer. The observed absolute risk difference in VTE recurrence in favor of apixaban was 11.9% in patients with gynecological, 5.5% with lung, 3.7% with genitourinary cancer, and 0.6% with gastrointestinal cancer. None of the risk differences was statistically significant. The rates of major bleeding in patients treated with apixaban or dalteparin was similar across patients with different cancer sites. In conclusion, recurrences appear to be more common in patients with gastrointestinal and gynecological cancer and major bleedings in patients with genitourinary and gastrointestinal cancer. Oral apixaban is a valid oral alternative to subcutaneous dalteparin for the treatment of a large spectrum of patients with cancer-associated VTE.

scholarly journals Safety of Anticoagulant Therapies for Treatment of Venous Thromboembolism in Patients with Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1178-1178 ◽  
Author(s):  
Michael Streiff ◽  
Dejan Milentijevic ◽  
Keith McCrae ◽  
Daniel Yannicelli ◽  
Jonathan Fortier ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Hazard Ratio ◽  
Control Cohort ◽  
Bleeding Events ◽  
Employment Equity ◽  
Patients With Cancer ◽  
Equity Ownership ◽  
Major Bleeding Events

Abstract Introduction: Anticoagulation is effective for the treatment of venous thromboembolism (VTE) in cancer patients, but it is also associated with an increased risk of bleeding. Previous clinical trials (e.g., CLOT and CATCH) of LMWH and warfarin for the treatment of VTE in cancer patients reported major bleeding in 3% to 6% of treated patients. The objective of this observational study was to compare the risk of major bleeding in cancer patients treated with anticoagulants for VTE in a real world setting. Methods: Medical and pharmacy claims from the Humana Database from 1/1/2013 to 05/31/2015 were analyzed. Newly diagnosed cancer patients with a first VTE diagnosis occurring after their first cancer diagnosis, and with ≥1 dispensing of an anticoagulant within 7 days after their VTE diagnosis, were selected. Based on the first anticoagulant received, patients were classified into one of the following cohorts: LMWH, warfarin, and rivaroxaban (other agents not included due to low utilization). Inverse probability of treatment weights based on propensity score were used to adjust for differences between treatment cohorts for the following comparisons: LMWH vs. rivaroxaban, LMWH vs. warfarin, and rivaroxaban vs. warfarin. Patients were followed up until the earliest event, either treatment non-persistence (gap > 60 days between the end of the days of supply of a dispensing and the start date of the next dispensing), or end of data availability. Major bleeding events were identified using validated criteria (Cunningham et al., 2011). Kaplan-Meier rates at 3 and 6 months and Cox proportional hazards models were used to compare the risk of bleeding between different treatment cohorts. To better understand the risk of major bleeding in cancer patients unrelated to anticoagulation, a cohort of patients with cancer who did not have VTE and did not receive an anticoagulant was added as a control cohort. Results: A total of 2,428 patients (LMWH: n=660; warfarin: n=1,061; rivaroxaban: n=707) were included. Baseline demographic and clinical characteristics were well balanced among treatment cohorts. Median duration of therapy with LMWH was shorter than rivaroxaban (1.0 vs. 3.0 months, p<.0001) and warfarin (1.0 vs. 3.5 months, p<.0001). Rates of major bleeding for LMWH and rivaroxaban were 8.3% and 8.2%, respectively at 6 months with a hazard ratio (HRs [95% CI]) of 1.03 (0.64-1.65; Figure 1A). In the comparison between LMWH and warfarin cohorts, major bleeding rates were 8.5% and 8.6%, respectively at 6 months with hazard ratio (HRs [95% CI]) of 1.04 (0.69-1.57; Figure 1B). The risk of major bleeding was also similar for rivaroxaban and warfarin cohorts, 9.0% and 8.7%, respectively at 6 months with a hazard ratio (HR [95% CI]) of 1.01 (0.71-1.43; Figure 1C). For the control cohort of cancer patients without VTE and not receiving anticoagulation median follow-up was 5.6 months. Rates of major bleeding events for the control cohort were 2.6% and 4.2 % at 3 and 6 months, respectively. Conclusion: This real world study of cancer patients treated for VTE found that the risk of major bleeding was similar for the 3 most widely prescribed anticoagulants in current clinical practice: LMWH, warfarin, and rivaroxaban. The observed rates of major bleeding were generally higher than what has been reported for LMWH and warfarin in the CLOT and CATCH trials. Patient characteristics such as older age (average age 73 years) could have contributed to the higher major bleeding rate seen in this study compared to the CLOT and CATCH trials, respectively. Figure 1 Rates of Major Bleeding Events LMWH vs. rivaroxaban cohorts Figure 1. Rates of Major Bleeding Events. / LMWH vs. rivaroxaban cohorts Figure 2 LMWH vs. warfarin cohorts Figure 2. LMWH vs. warfarin cohorts Figure 3 rivaroxaban vs. warfarin cohorts Figure 3. rivaroxaban vs. warfarin cohorts Disclosures Streiff: Portola: Research Funding; Janssen: Consultancy, Research Funding; Roche: Research Funding; CSL Behring: Consultancy, Research Funding. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. McCrae:Janssen: Membership on an entity's Board of Directors or advisory committees. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Pharmaceuticals: Research Funding. Nelson:Janssen Scientific Affairs: Employment, Equity Ownership. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Khorana:Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

A meta-analysis of anticoagulants as cancer treatment: Impact on survival and bleeding complications

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9071-9071
Author(s):  
N. M. Kuderer ◽  
A. A. Khorana ◽  
G. H. Lyman ◽  
C. W. Francis
Keyword(s):  
Relative Risk ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Bleeding Complications ◽  
Primary Study ◽  
Bleeding Events ◽  
Impact On Survival ◽  
The Impact ◽  
Overall Mortality

9071 Background: There is substantial laboratory evidence that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, while clinical trials have reported conflicting results. This study represents the first comprehensive systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs) evaluating specifically the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism (VTE). Methods: An exhaustive systematic literature review of RCTs was performed without language restrictions, including a comprehensive search of electronic databases through May 2006 with subsequent weekly updates to the end of 2006 (Medline, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, DARE, and major conference proceedings) and relevant article references. Two reviewers extracted the data independently. Primary study outcomes were 1-year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes. The meta- analysis was performed utilizing the Mantel-Haenszel method. Results: All identified 11 RCTs were performed in solid tumor patients. Anticoagulation significantly decreased overall mortality across all studies with a relative risk (RR) of 0.905 (95%CI: 0.847–0.967; p=0.003). The survival improvement appears not to be due to the prevention of fatal VTE. All bleeding complications (RR=2.309; 95%CI: 1.928–2.764; p<0.0001) and major bleeding events (RR=2.598; 95%CI; 1.936–3.488; p<0.0001) occurred more frequently with anticoagulation. The relative risk for mortality was 0.877 (95%CI: 0.789–0.975; p=0.015) with LMWH, compared to warfarin (RR=0.942; 95%CI: 0.854–1.040; p=0.239). Warfarin resulted in higher rates for all and major bleeding complications compared to LMWH (p<0.0001, respectively). Conclusions: Anticoagulants significantly improved overall survival in cancer patients while increasing the risk of bleeding complications. Despite these encouraging findings, given limitations of available data and the potential for life-threatening complications, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results. No significant financial relationships to disclose.

Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

2018 ◽  
Vol 118 (01) ◽  
pp. 174-181 ◽  
Author(s):  
Noémie Kraaijpoel ◽  
Nick van Es ◽  
Suzanne Bleker ◽  
Marjolein Brekelmans ◽  
Elise Eerenberg ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Phase Iii ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractCancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47–1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35–1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

scholarly journals A Systematic Review and Meta-Analysis of Randomized Trials Examining Extended Thromboprophylaxis with Direct Oral Anticoagulants in Hospitalized Medical Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1436-1436 ◽  
Author(s):  
Derrick Tao ◽  
Jeffery Bien ◽  
Joseph Shatzel
Keyword(s):  
Major Bleeding ◽  
Randomized Trials ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Bleeding Event ◽  
Absolute Risk Reduction ◽  
Pooled Analysis ◽  
Risk Difference ◽  
Medical Patients ◽  
Extended Course

Abstract INTRODUCTION: Thromboprophylaxisduring hospitalization is an accepted intervention to prevent hospital related venous thromboembolism (VTE), however VTE still occurs post discharge. Recently, several randomized trials have compared extended prophylaxis with a direct oral anticoagulant (DOAC) for a prolonged period after hospital discharge to standard short-course prophylaxis with low molecular weight heparin (LMWH) in acutely-ill medical patients. While DOACs offer a convenient means to prevent post-hospitalization VTE, it remains unclear if this intervention has a positive risk-benefit ratio in the overall population of acutely hospitalized medical patients. To better answer this, we performed the following systematic review and meta-analysis. METHODS: We performed a systematic literature search in Medline using PUBMED in an attempt to identify all relevant randomized clinical trials comparing extended prophylaxis with any DOAC to standard course prophylaxis in hospitalized medical (non-surgical) patients. We extracted data on study design and characteristics, total VTE, symptomatic VTE, total bleeding, and major bleeding. Pooled relative risk (RR) was calculated with a corresponding 95% confidence interval (CI) using a Mantel-Haneszelrandom-effects model. Absolute risk differences and the number needed to treat (NNT) or number needed to harm (NNH) were generated along with Forest plots. RESULTS: Our search identified 338 individual publications, of which 313 were excluded on initial screening by title and abstract. Full text were obtained of the remaining 25 studies and independently reviewed by two physicians, of which 22 were excluded for the following reasons: Comments on other articles (12), Study Protocol (1), Review article (8), Data unavailable (1). A total of three trials, enrolling 22,142 patients, were included. Apixaban, rivaroxaban, andbetrixabanwere each evaluated by one study. Among the studies, 11,064 patients were randomized to extended DOAC prophylaxis, while 11,078 were randomized to standard course LMWH prophylaxis. In pooled analysis, VTE (including screened asymptomatic VTE) occurred in 4.30% of the patients receiving extended DOAC prophylaxis and 5.61% of patients treated with standard course LMWH (RR 0.76 [95% CI, 0.67-0.87], P = <0.0001, I2 = 0%). The NNT was 76. Symptomatic VTE occurred in 1.11% of patients treated with extended course DOACs and 1.68% patients treated with standard course LMWH. DOAC extended prophylaxis was associated with a significant reduction in symptomatic VTE (RR 0.66 [95% CI, 0.51-0.86], P = 0.002, I2 = 0%). The pooled absolute risk reduction was 0.57%, with a NNT of 176. A bleeding event occurred in 4.82% of patients receiving extended course DOACs compared to 3.16% of patients receiving standard course LMWH. The pooled analysis demonstrates a statistically relevant increase in bleeding (RR 1.74 [95% CI, 1.05-2.90], P < 0.001, I2 = 92%), with an absolute risk difference of 1.67% and a NNH of 60. A major bleeding event occurred in 0.59% of patients treated with extended course DOACs and 0.35% of patients treated with standard course LMWH. DOAC extended prophylaxis was associated with a significantly increased rate of major bleeding (RR 1.71 [95% CI, 1.07-2.75], P = 0.03, I2 = 23%). The pooled absolute risk difference is 0.24% with a NNH of 417. CONCLUSIONS: In this pooled analysis, extendedthromboprophylaxiswith DOACs was associated with a significant decrease in total and symptomatic VTEin medical patientsas compared to standard course LMWH. However, the low rate of symptomatic VTE, low absolute risk reduction, and significantly increased rate of bleeding with extended prophylaxis calls into questions if this intervention should be used. Table Table. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment and Outcomes in Heparin-Induced Thrombocytopenia (HIT) in Patients with Neoplasm: A Single Centre Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4951-4951 ◽  
Author(s):  
Chieh Min Lai ◽  
Tyler Smith ◽  
Agnes Yuet Ying Lee
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Single Centre ◽  
Bleeding Events ◽  
Heparin Induced Thrombocytopenia ◽  
Patients With Cancer ◽  
Cancer Group

Background: Heparin-induced thrombocytopenia (HIT) is an immune mediated, pro-thrombotic disorder associated with exposure to heparin and a substantial number of patients develop thrombosis (HITT) in the venous, arterial, or microvascular system. Treatment includes cessation of heparin and starting a non-heparin anticoagulant. Patients with cancer are already at high risk of venous thromboembolism (VTE) as well as recurrent VTE despite anticoagulant therapy and are also at higher risk of bleeding compared with patients without cancer. Consequently, cancer patients may not share similar outcomes as patients without cancer in the setting of HIT. We conducted a single-centre, retrospective study to evaluate baseline characteristics, treatments and outcomes in HIT patients with and without cancer. Methods: Medical records of all patients seen at our tertiary centre between November 1, 2006 and December 31, 2016 who tested positive for HIT antibodies and had a 4T score of 4 or higher were reviewed. Patients with cancer were defined as those who had any evidence of cancer, including myeloproliferative neoplasm (MPN), and/or receiving cancer treatment within 6 months prior to HIT diagnosis. Details of treatments and outcomes were captured up to 6 months after start of HIT treatment. Comparative statistics was performed between the cancer and non-cancer cohorts. Results: We identified 95 patients with confirmed HIT, of whom 39 (41%) had cancer and 41 (43%) had HITT as the index event. The mean age was 65 years (standard deviation 16) and 59% were female. Thirty (77%) cancer patients had at least 3 months of available records and 26 (67%) had at least 6 months, while 37 (66%) non-cancer patients had at least 3 months of available records and 27 (48%) had at least 6 months. Baseline demographics including cancer types are summarized in Table 1. The most common malignancy was polycythemia vera (PV), with those with MPN (7 PV, 2 essential thrombocythemia) representing 23% of the patients with cancer. Cancer patients were more likely to have a history of thromboembolic events prior to index heparin exposure and HIT diagnosis (79.5% vs. 53.6%, p=0.02) than those without cancer. Among patients with HITT, the two groups had similar incidences of pulmonary embolism and/or deep vein thrombosis, although a higher proportion of the non-cancer group had clots in other non-classic locations (32.1% vs. 10.3%, p=0.01) such as splanchnic thrombosis. A variety of non-heparin agents were used, including direct oral anticoagulants (Table 2), with most patients receiving either fondaparinux or argatroban followed by warfarin. The cancer group received fondaparinux more often than the non-cancer group (87.2% vs. 64.3%, p=0.02). In those alive with at least 6 months of follow-up, the median duration of non-heparin anticoagulation was 180 days for both cancer patients and non-cancer patients. During follow-up, 16 (17%) patients had a thrombotic event, 15 (16%) had major bleeding and 11 (12%) died among the 95 patients with HIT. The rates of subsequent thrombosis, bleeding events, and death were similar between the two cohorts over the 6-month follow-up period (Table 3). None of the deaths were from thrombotic or bleeding events but the cause of death for one patient with cancer was unknown. Conclusion: Patient outcomes following a diagnosis of HIT appear similar between patients with and without cancer, with high rates of subsequent thrombosis and major bleeding. Patients with MPN might have a higher risk of HIT. Further studies are warranted to confirm these findings and determine if direct oral anticoagulants might be efficacious and safe in patients with HIT. Disclosures Lee: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. OffLabel Disclosure: Direct oral anticoagulants and fondaparinux were used as non-heparin anticoagulants for the treatment of heparin induced thrombocytopenia.

scholarly journals Efficacy and safety of thromboprophylaxis in cancer patients: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592090754
Author(s):  
Miao Liu ◽  
Guiyue Wang ◽  
Yuhang Li ◽  
Hongliang Wang ◽  
Haitao Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Patients With Cancer ◽  
Significant Difference ◽  
All Cause Mortality ◽  
The Cochrane Library

Background: Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could benefit patients with cancer is unclear. The aim of this systematic review was to determine the efficacy and safety of thromboprophylaxis in patients with cancer undergoing surgery or chemotherapy. Methods: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2018 to investigate whether thromboprophylaxis measures were more effective than a placebo in patients with cancer. Results: In total, 33 trials with 11,942 patients with cancer were identified. In patients with cancer undergoing surgery, the administration of thromboprophylaxis was associated with decreasing trends in venous thromboembolism (VTE) [relative risk (RR) 0.51, 95% confidence interval (CI) 0.32–0.81] and DVT (RR 0.53, 95% CI 0.33–0.87). In patients with cancer undergoing chemotherapy, the administration of thromboprophylaxis reduced the incidences of VTE, DVT, and pulmonary embolism compared with no thromboprophylaxis (RR 0.54, 95% CI 0.40–0.73; RR 0.47, 95% CI 0.31–0.73; RR 0.51, 95% CI 0.32–0.81, respectively). The pooled results regarding major bleeding showed no significant difference between prophylaxis and no prophylaxis in either the surgical or the chemotherapy groups (RR 2.35, 95% CI 0.74–7.52, p = 0.1482, I2 = 0%; RR 1.30, 95% CI 0.93–1.83, p = 0.1274, I2 = 0%, respectively). Conclusion: Thromboprophylaxis did not increase major bleeding events or the incidence of thrombocytopenia. All-cause mortality was not significantly different between those who received thromboprophylaxis and those who did not. This meta-analysis provides evidence that thromboprophylaxis can reduce the number of VTE and DVT events, with no apparent increase in the incidence of major bleeding in patients with cancer.

Risk of Bleeding from Primary Thromboprophylaxis (PTP) in Patients with Solid Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3820-3820
Author(s):  
Kyaw Zin Thein ◽  
Aung M Tun ◽  
Sai-Ching J Yeung ◽  
Thein H. Oo
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Risk Difference ◽  
Control Group ◽  
Solid Cancer ◽  
Bleeding Events ◽  
Risk Of Bleeding

Abstract Introduction: Thrombosis is the second leading cause of death in cancer patients. Hypothetically, prognosis might be improved by preventing thrombotic events by PTP. PTP has to be outweighed with the bleeding risk from PTP benefit. Moreover, PTP in ambulatory cancer patients remains uncertain. We performed a systematic review and meta-analysis of RCTs to determine the risk of major bleeding (MB) and clinically relevant non-major (CRNM) bleeding from PTP with low-molecular weight heparins (LMWH) in solid cancer patients receiving chemotherapy. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through May 31, 2016. The RCTs with MB and CRNM bleeding as safety outcomes were included in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Random effects model was applied. Results: 12 RCTs with a total of 8643 patients were eligible for analysis. Dalteparin, nadroparin, certoparin, semuloparin and bemiparin were used in the studies. 9 studies utilized prophylactic doses, while one used intermediate doses and 2 employed therapeutic dose. The PTP duration was from 6 weeks to 6 months. MB events were reported in 67 (1.486%) patients on PTP compared to 46 (1.112%) in control group. The pooled RR for MB was statistically nonsignificant at 1.341 (95% CI: 0.917 to 1.960, P = 0.130). CRNM bleeding events were noted in 209 (4.637%) in PTP group and 106 (2.563%) in control group. The RR for CRNM bleeding was statistically significant at 1.729 (95% CI: 1.017 to 2.938, P = 0.043). The absolute RD in CRNM bleeding was 0.020 (95% CI: 0.004 to 0.035, P = 0.012) with an estimated number needed to harm (NNH) of 48 to cause one CRNM bleeding event. Conclusions: Approximately 60 patients are needed to be treated with PTP to prevent one symptomatic venous thrombosis among all ambulatory unselected cancer patients on chemotherapy in a previous meta-analysis. Our meta-analysis revealed that PTP contributed an increase in CRNM bleeding events with NNH of 48. The risk of bleeding should not be underestimated and more RCTs are required before making any recommendations. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Oo: Daiichi Sankyo: Research Funding.

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