Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer

Abstract Context: A substantial clinical need exists for an alternate to vitamin-K-antagonists for treating deep-vein thrombosis in many patients. Long-term low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and may be associated with less harm due to thrombocytopenia. Objective: Considerable evidence suggests that reporting of harms-related data* from randomized clinical trials needs improvement. In accordance with CONSORT* we present a harm analysis regarding thrombocytopenia. Design: Randomized clinical trial using objective outcome measures. Setting: 30 centres across Canada. Participants: Acute symptomatic proximal-vein thrombosis patients. Intervention: Therapeutic tinzaparin subcutaneously once-daily, or intravenous unfractionated heparin/oral vitamin-K-antagonist therapy for 3 months. Main Outcome Measures: Benefit was assessed by assessing the frequency of symptomatic objectively documented recurrent venous thromboembolism and harm by objectively documented hemorrhagic complications and the outcome of thrombocytopenia. Results: Benefit and bleeding harm are reported elsewhere. Long-term low-molecular-weight heparin treatment was at least as effective but associated with less harm due to bleeding than usual care. Thrombocytopenia occurred in 21 of 369 (5.7%) patients receiving tinzaparin versus 9 of 368 (2.4%) patients receiving usual care (absolute difference 3.3). Six of 9 patients with thrombocytopenia receiving usual care died (66.7 percent, 95 percent confidence interval 29.9 to 92.5) versus 4 of 21 with thrombocytopenia receiving low-molecular-weight heparin (19 percent, 95 percent confidence interval 5.4 to 41.9 percent) (absolute difference 47.6 percent, 95 percent confidence interval 82.7 to 12.5 percent, p=0.03). Recurrent venous thromboembolism occurred infrequently in patients with thrombocytopenia. Conclusion: Our findings suggest that harm associated with thrombocytopenia in patients receiving intravenous unfractionated heparin versus low-molecular-weight heparin favors low-molecular-weight heparin use. Further evaluation in rigorous trials is required.

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A randomized trial of the effect of low molecular weight heparin vs. warfarin on mortality in the long-term treatment of proximal vein thrombosis

Intensivmedizin + Notfallmedizin ◽

10.1007/s003900070014 ◽

2000 ◽

Vol 37 (9) ◽

pp. S123-S132 ◽

Cited By ~ 8

Author(s):

R. D. Hull ◽

G. F. Pineo ◽

R. F. Brant

Keyword(s):

Molecular Weight ◽

Randomized Trial ◽

Low Molecular Weight Heparin ◽

Term Treatment ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Long Term Treatment

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Low Molecular Weight Heparin in Patients with Cancer: A New Option

Blood ◽

10.1182/blood.v112.11.4058.4058 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4058-4058

Author(s):

Giorgio Corinaldesi ◽

Christian Corinaldesi

Keyword(s):

Molecular Weight ◽

Cancer Biology ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Minor Bleeding ◽

Vein Thrombosis ◽

Patients With Cancer ◽

Cancer Breast ◽

Metastatic Activity ◽

Deep Vein

Abstract The use of heparin for venous thromboembolism, upper extremity deep vein thrombosis (DVT), septic thrombophlebitis, loss of central venous device access in patients with cancer is a standard practice; a new clinical evidence suggest that low molecular weight heparin (LMWHs) may prolong survival in patients with cancer and may have anti-neoplastic effects and anti-metastatic activity. We evaluated 74 patients with cancer (38 patients were allocated to enoxaparin 6000UI subcutaneously once a day, and 36 patients were allocated to placebo), the mean duration of follow-up was 12 months, platelet count were performed before the treatment, and once a month; in the event of thrombocytopenia < 50.000/ml or abnormal bleeding the treatment was stopped. The primary end points were overall survival, and metastasis progression. TAB:A Enoxaparin (n.38) Placebo (n.36) Age-years (range) 46–68 48–66 Sex (male/female) 20/18 20/16 Metastasis disease a) before 10 12 b) end-therapy 12 18 Type of cancer Breast cancer 8 8 Endometrial cancer 6 5 Gastric or esophageal 4/2 3/1 Colorectal cancer 6/2 8/2 Prostatic cancer 6 7 Urothelial 2 1 Lung 2 1 Death 3 8 Major bleeding 1 0 Minor bleeding 4 4 Allergic reaction 0 0 VTE 6 0 Concomitant anti-neoplastic therapy Chemotherapy 26 26 Radiotherapy 2 1 Combined 4 3 Hormonal 6 6 These data show that LMWHs reduce or attenuate metastasis at 12 month by 11.4%, and death by 8.8%, with a significant increase of median survival. Heparin have show to have direct antigrowth, antiangiogenesis, and antimetastatic effects, LMWHs minimize angiogenesis with the inhibition of VEGF and b-FGF, inhibit the adhesion of cancer cells to endothelium and the interaction mediated by tumor cells surface mucins and selectin, and they interfere with cancer biology; we can speculate that the binding of tumor growth to heparin have a crucial role in the modulation of activity of the high affinity receptors, it promotes receptors dimerization and activation, inhibits P and L-selectins and chemokine action (IL-8, Mip-1), blocks MMP, serin-protease and heparanase, decreases over-expression of TF and PAF, induces and increases apoptosis.

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A randomized trial of the effect of low molecular weight heparin vs. warfarin on mortality in the long-term treatment of proximal vein thrombosis

Acute Pulmonary Embolism ◽

10.1007/978-3-642-51190-5_15 ◽

2000 ◽

pp. 161-174

Author(s):

R. D. Hull ◽

G. F. Pineo ◽

R. F. Brant

Keyword(s):

Molecular Weight ◽

Randomized Trial ◽

Low Molecular Weight Heparin ◽

Term Treatment ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Long Term Treatment

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Self-Managed Long-Term Low-Molecular-Weight Heparin Compared with Usual-Care Anticoagulation for Patients with Proximal Venous Thrombosis: Harm Associated with Bleeding!.

Blood ◽

10.1182/blood.v106.11.901.901 ◽

2005 ◽

Vol 106 (11) ◽

pp. 901-901 ◽

Cited By ~ 1

Author(s):

Russell D. Hull ◽

Graham F. Pineo ◽

Rollin F. Brant ◽

Keyword(s):

Molecular Weight ◽

Usual Care ◽

Vitamin K ◽

Low Molecular Weight Heparin ◽

Vitamin K Antagonists ◽

Absolute Difference ◽

Low Molecular Weight ◽

Heparin Group ◽

Vein Thrombosis ◽

Hemorrhagic Complications

Abstract Context: A substantial clinical need exists for an alternate to vitamin-K-antagonists for treating deep-vein thrombosis in many patients. Long-term low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and may be associated with less harm due to bleeding. Objective: Considerable evidence suggests that reporting of harms-related data* from randomized clinical trials needs improvement. In accordance with CONSORT* we present a harm analysis regarding hemorrhagic complications. Design: Randomized clinical trial using objective outcome measures. Setting: 30 centres across Canada. Participants: Acute symptomatic proximal-vein thrombosis patients. Intervention: Therapeutic tinzaparin subcutaneously once-daily, or usual-care intravenous unfractionated heparin/vitamin-K-antagonists for 3 months. Main Outcome Measures: Benefit was assessed by assessing the frequency of symptomatic objectively documented recurrent venous thromboembolism and harm by objectively documented hemorrhagic complications. Results: A broad-spectrum of patients was randomized. Of 737 patients, 18 of 369 receiving tinzaparin (4.9 percent) suffered recurrent venous thromboembolism at three months compared with 21 of 368 (5.7 percent) receiving usual-care; (absolute difference, −0.9 percent, 95 percent confidence interval −4.1 to 2.4). Hemorrhagic complications occurred less frequently in the low-molecular-weight heparin group; 48 of 369 patients, (13.0 percent) versus usual-care 73 of 368, (19.8 percent), (absolute difference −6.8 percent; p=0.011; risk ratio = 0.66). The prevalence of major bleeding according to the duration of study treatment favored low-molecular-weight heparin therapy. Major bleeding persisted throughout study treatment for patients in the usual-care group receiving warfarin but ceased early by day 23 in the low-molecular-weight heparin group (p=0.034). Twenty-five patients (6.8 percent) in the low-molecular-weight heparin group and 24 patients (6.5 percent) receiving usual-care died (absolute difference 0.3 percent, 95 percent confidence interval −3.4 to 3.9). Conclusion: Our findings are clinically relevant and important, offering the clinician an alternate therapy to vitamin-K-antagonist therapy which does not require anticoagulant monitoring in a wide range of patients with proximal venous thrombosis. Self-management with once-daily subcutaneous tinzaparin was at least as effective as usual-care and vitamin-K-antagonist therapy and offers a safety advantage with less harm due to bleeding.

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Anti-Xa monitoring of low-molecular-weight heparin in adult patients with cancer

Hematology ◽

10.1182/asheducation-2016.1.206 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 206-207 ◽

Cited By ~ 3

Author(s):

Lisa Baumann Kreuziger ◽

Michael Streiff

Keyword(s):

Prostate Cancer ◽

Molecular Weight ◽

Pulmonary Embolism ◽

Low Molecular Weight Heparin ◽

Femoral Vein ◽

Stage Iv ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Patients With Cancer ◽

Deep Vein

Abstract A 68-year-old man developed a right femoral vein deep vein thrombosis and bilateral pulmonary embolism while receiving chemotherapy for stage IV prostate cancer. His creatinine at diagnosis is 1.4 mg/dL, with an estimated clearance of 63 mL/min. In patients with cancer, should low-molecular-weight heparin treatment be dosed according to weight, or adjusted using anti-Xa levels?

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