Utilization and effectiveness of extended-duration thromboprophylaxis after high-risk abdominopelvic cancer surgery.

62 Background: Extended-duration thromboprophylaxis for 4 weeks after discharge has been demonstrated to reduce venous thromboembolic events (VTE) in cancer patients undergoing abdominopelvic surgery and is recommended in national guidelines. We examined the utilization and effectiveness of extended-duration low molecular weight heparin prophylaxis in high-risk cancer patients after surgery. Methods: We analyzed patients with colon, ovarian, and uterine cancer who underwent surgery from 2009-2013 and who were recorded in the MarketScan database. Multivariable models and propensity score analysis with inverse probability of treatment weights were developed to examine uptake and predictors of use of post-discharge low molecular weight heparin (LMWH) use, VTE incidence, and associated adverse events (transfusion, and hemorrhage). Results: A total of 63,280 patients were identified. Use of extended-duration prophylaxis increased from 2009 to 2013 from 1.4% to 1.7% (P = 0.67) for colectomy, 5.9% to 18.3% for ovarian cancer surgery (P < 0.001), and 6.3% to 12.2% (P < 0.001) for hysterectomy for endometrial cancer. There was no association between use of extended-duration prophylaxis and reductions in VTE for any of the procedures: colectomy (2.4% with extended-duration prophylaxis vs. 2.9% without prophylaxis, OR = 0.84; 95% CI, 0.54-1.31), ovarian cancer-directed surgery (3.7% vs. 3.6%, OR = 1.01; 95% CI, 0.76-1.33), hysterectomy (2.1% vs. 2.1%; OR = 0.96; 95% CI, 0.67-1.38). Extended-duration prophylaxis was associated with an increased risk of adverse postoperative events: 2.20 (95% CI, 1.51-3.19) after colectomy, 1.24 (95% CI, 0.92-1.68) following ovarian cancer-directed surgery and 0.99 (95% CI, 0.66-1.48) for hysterectomy for endometrial cancer. Conclusions: Use of extended-duration thromboprophylaxis is low among high-risk cancer patients undergoing surgery. The effectiveness of prophylaxis in real world populations requires further evaluation.

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Cancer Patients Requiring Interruption of Long-Term Anticoagulant Therapy: The Use of Fixed Sub-Therapeutic Doses of Low-Molecular Weight Heparin

Blood ◽

10.1182/blood.v118.21.1244.1244 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1244-1244

Author(s):

Giorgia Saccullo ◽

Alessandra Malato ◽

Lucio Lo Coco ◽

Ilenia Barbello ◽

Clementina Caracciolo ◽

...

Keyword(s):

Molecular Weight ◽

High Risk ◽

Cancer Patients ◽

Low Molecular Weight Heparin ◽

Risk Group ◽

Low Risk ◽

Major Surgery ◽

Low Molecular Weight ◽

Therapeutic Doses ◽

Risk For Thrombosis

Abstract Abstract 1244 Introduction. We tested the efficacy and safety of fixed doses of Low-Molecular Weight Heparin (LMWH) in cancer patients requiring interruption of Vitamin-k Antagonist (VKA) because of invasive procedures (defined as major and non major surgery) or chemotherapy inducing platelets depletion. Methodology. Cancer patients were defined to be at high (atrial fibrillation [AF] with previous stroke, prosthetic mitralic valves and venous thromboembolism [VTE] lasting < 3months) or low risk of thrombosis (AF without previous stroke, VTE lasted > 3 months, and prosthetic aortic valves). They discontinued VKA 5 + 1days before surgery or chemotherapy; in those at low-risk for thrombosis, LMWH was given at a prophylactic dosage of 3.800 U.I. (nadroparin) or 4.000 U.I. (enoxaparin) anti-FXa once daily the night before the procedure or the beginning of chemotherapy. In patients at high-risk for thrombosis, LMWH was started early after VKA cessation (when an INR < 1.5) and given at fixed sub-therapeutic doses (3.800 or 4.000 UI anti-FXa twice daily) until procedure or beginning of chemotherapy. In patients undergoing procedures, LMWH was reinitiated 12 hours after procedure while VKA the day after; in patients receiving chemotherapy, LMWH was reinitiated 12 h after a stable platelet count > 30.000 mmc3 and VKA 12 h after a stable platelet count > 50.000 mmc3. Heparin was continued until a therapeutic INR value was reached. The primary efficacy endpoints were the incidence of thromboembolism and major bleeding from VKA suspension to 30 + 2 days post-procedure or next chemotherapy. Results. A total of 156 patients (68, 53.9% at low-risk and 58, 46.1% at high-risk for thrombosis) were enrolled (Table 1); 44 (28.2%) underwent major surgery, 53 (33.9%) non-major surgery and 29 (18.5%) chemotherapy. Overall, thromboembolic events occurred in 5 patients (3.2%, 95% confidence intervals 0.5–5.9), 4 belonging to high-risk and 1 to low-risk group. Overall, major bleeding occurred in 5 patients (3.2%, 95 CI 0.5–5.9), all belonging to high-risk group (3 during major surgery and 2 during chemotherapy). The mean time of anticoagulation with LMWH was 7.5 days in patients underwent procedures and 13.2 days in those who received chemotherapy. Conclusion. LMWH given at fixed sub-therapeutic doses appears to be a feasible and relatively safe approach for bridging therapy in chronic anticoagulated cancer patients requiring VKA interruption. Disclosures: No relevant conflicts of interest to declare.

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Do differences in baseline clinical severity of ovarian cancer patients with thrombosis predict treatment with rivaroxaban versus low molecular-weight heparin?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18748 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18748-e18748

Author(s):

Christine G. Kohn ◽

Jonathan T. Caranfa ◽

Molly Brewer ◽

Meghana Singh ◽

Craig I. Coleman ◽

...

Keyword(s):

Ovarian Cancer ◽

Molecular Weight ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Low Molecular Weight Heparin ◽

Univariate Analysis ◽

Clinical Severity ◽

Low Molecular Weight ◽

Routine Practice ◽

Ckd Stage

e18748 Background: Prescribers use direct oral anticoagulants and low molecular-weight heparin (LMWH) for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT). We sought to identify predictors impacting the use rivaroxaban versus LMWH for CAT in patients with ovarian cancer. Methods: Using US Surveillance, Epidemiology and End Result-Medicare linked data from 2013-2016, we evaluated adults with ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Univariate analysis was performed to examine the association between covariates and clinicians’ choice to use rivaroxaban or LMWH. Variables with a p-value < 0.20 upon univariate analysis were deemed significant and subsequently included into a stepwise, backwards multivariable logistic regression model to obtain adjusted odd ratios (ORs) of treatment assignment. Results: Of the 125 ovarian cancer patients included in our analysis, 26% received rivaroxaban and 74% LMWH. All patients had stage 3 or 4 ovarian cancer, 36% were ≥75 years-of-age, 78% were white, and 18% were below the poverty line (p ≥ 0.25). Upon univariate analysis, rural community, time between cancer diagnosis and VTE ≥ 1 year, index VTE without evidence of pulmonary embolism, and CKD ≥ stage 3 were found to be significant predictors of rivaroxaban use when compared to LMWH (p ≤ 0.14 for all). Upon multivariable regression, CKD ≥ stage 3 (OR = 3.13) was shown to be independently associated with rivaroxaban versus LMWH use (p≤0.01). Conclusions: In routine practice, patients were more likely to receive rivaroxaban if they had CKD and lived in a rural area. These differences in prescribing practices may be due to less availability of LMWH in rural areas and less tolerance of injections in CKD patients. Univariate analysis also suggest that low VTE burden (i.e., DVT only) and VTE event ≥ 1 year after cancer diagnosis were also associated with rivaroxaban use over LMWH, which may be due to LMWH therapy as the long-established standard of care for patients with cancer. Large observational studies are needed to confirm these results. [Table: see text]

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Low Molecular Weight Heparin Modulates Thrombin Generation in Cancer Patients Undergoing Antithrombotic Therapy for Overt Venous Thromboembolism

Blood ◽

10.1182/blood.v124.21.1539.1539 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1539-1539

Author(s):

Anna Falanga ◽

Carmen J Tartari ◽

Marina R Marchetti ◽

Laura Russo ◽

Kim WFM Lambregts ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

High Risk ◽

Cancer Patients ◽

Low Molecular Weight Heparin ◽

Thrombin Generation ◽

Procoagulant Activity ◽

Low Molecular Weight ◽

Cancer Associated Thrombosis ◽

D Dimer

Abstract Introduction The incidence and recurrence rate of venous thromboembolism (VTE) are increased in the cancer compared to the non-cancer population. Low molecular weight heparin (LMWH) is recommended for both initial and long-term anticoagulant therapy for cancer-associated thrombosis, being more effective and safer than vitamin K antagonist therapy. However, failure of anticoagulation with LMWH in cancer-associated thrombosis still remains significantly elevated (VTE recurrence = 9-15%). In this study we tested whether thrombin generation (TG), a global hemostatic assay, may represent a modality to evaluate the LMWH anticoagulant level in vivo and help identifying patients at high risk for VTE recurrences. In a prospective cohort of cancer patients with VTE receiving LMWH nadroparin 200 U.I./Kg once a day, we evaluated whether LMWH treatment modulated the plasma TG capacity, together with other hemostatic parameters, i.e. microparticle (MP)-associated procoagulant activity (PCA) and D-dimer levels. Second we wished to explore whether these parameters may predict for VTE recurrence and/or bleeding. Methods Fifty eight consecutive cancer patients with acute VTE were enrolled into the study. Plasma samples were obtained at the following time intervals: at the thrombotic event (T0), at 1 month LMWH therapy (T1), and at discontinuation (T2), i.e. 6 months after VTE. Patients were followed up clinically for a total 9 months to detect overt thrombotic or bleeding events. TG was measured by the CAT assay, MP-associated procoagulant activity (PCA) by the STA Procoag PPL assay, and D-dimer by HemosIL D-dimer test. Results In this study cohort, the most represented malignancies were colon (25.9%), breast (15.5%), lung (15.5%), and gastric cancer (13.8%). Thirty six patients had metastatic disease, 22 had a limited disease. The VTE sites were: subclavian (36.2%), femoro-popliteal (20.7%), pulmonary (13.8%), jugular (8.6%), and brachial (6.9%) veins. Six patients had simultaneous femoro-popliteal venous thrombosis and pulmonary embolism. At T0 patients were characterized by a procoagulant phenotype as reflected by increased TG potential, and elevated MP-associated PCA and D-dimer compared to controls. In particular, cancer patients displayed a higher levels (p<0.01) of endogenous thrombin potential (ETP) and peak of thrombin vs controls (ETP: 1612±538 vs 1210±344 nMol*min and peak: 305±123 vs 182±84 mMol). These data were accompanied by a significant increase in MP-associated PCA (i.e. shorter clotting time 58±18 vs controls 89±12 sec; p<0.01), and D-dimer plasma levels (1430±1615 vs controls 90±96 ng/ml; p<0.01). During LMWH nadroparin therapy, a significant reduction in both TG potential (ETP-T1: 1254±810 nMol*min) and D-dimer levels (397±697 ng/ml) occurred, and after LMWH discontinuation (T2), TG potential as well as D-Dimer levels rose back, becoming similar to the control values. Differently, no reduction in MP-associated PCA was observed during LMWH therapy. Twenty-seven patients (46.6%) died during follow-up because of cancer disease. No patients had VTE recurrence. The analysis according to the stage of disease showed a significant difference with a higher mortality rate among those with a metastatic stage (p < 0.01). No correlations were observed according to chemotherapy. Conclusion Our results show that LMWH therapy modulates the global thrombin generation capacity and affects the hypercoagulable state of cancer patients, whereas MP-PCA is insensitive to it. In this cohort LMWH treatment was effective (0% VTE recurrences) and safe (1 major bleeding episode). As no recurrences were observed, it was not possible to identify a predictive value for the biological parameters. It is worth to define in a large trial the clinical utility of the TG global coagulation assay to monitor LMWH anticoagulation levels in this high risk population. Disclosures No relevant conflicts of interest to declare.

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