Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease

Summary

We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or < 24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheterrelated thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease.

Keywords

Central venous catheter - thrombosis - heparin

• References

• 1 Male C, Chait P, Andrew M. et al. Central venous line-related thrombosis in children: association with central venous line location and insertion technique. Blood 2003; 101: 4273-8.
• 2 Harter C, Salwender HJ, Bach A. et al. Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy. A prospective comparison of silver-coated and uncoated catheters. Cancer 2002; 94: 245-51.
• 3 Madero L, Ruano D, Villa M. et al. Non-tunneled catheters in children undergoing bone marrow transplantation. Bone Marrow Transplant 1996; 17: 87-9.
• 4 Kumagai T, Sakamaki H, Tanikawa S. et al. Utility and safety of Hickman catheters for venous access after bone marrow transplantation. Intern Med 1998; 37: 286-91.
• 5 Biagi E, Arrigo C, Dell’Orto MG. et al. Mechanical and infective central venous catheter-related complications: a prospective nonrandomized study using Hickman and Groshong catheters in children with hematological malignancies. Support Care Cancer 1997; 05: 228-33.
• 6 McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med 2003; 348: 1123-33.
• 7 Bona RD. Central line thrombosis in patients with cancer. Curr Opin Pulm Med 2003; 09: 362-366.
• 8 Journeycake JM, Buchanan GR. Thrombotic complications of central venous catheters in children. Curr Opin Hematol 2003; 10: 369-74.
• 9 Jacobs BR. Central venous catheter occlusion and thrombosis. Crit Care Clin 2003; 19: 489-514.
• 10 Freytes CO. Thromboembolic complications related to indwelling central venous catheters in children. Curr Opin Oncol 2003; 15: 289-92.
• 11 Bona RD. Thrombotic complications of central venous catheters in cancer patients. Semin Thromb Hemost 1999; 25: 147-55.
• 12 Monreal M, Raventos A, Lerma R. et al. Pulmonary embolism in patients with upper extremity DVT associated to venous central lines: a prospective study. Thromb Haemost 1994; 72: 548-50.
• 13 Anderson AJ, Krasnow SH, Boyer MW. et al. Thrombosis: the major Hickman catheter complication in patients with solid tumor. Chest 1989; 95: 71-75.
• 14 Klerk CP, Smorenburg SM, Büller HR. Thrombosis prophylaxis in patient populations with a central venous catheter: a systematic review. Arch Intern Med 2003; 163: 1913-21.
• 15 Carr KM, Rabinowitz I. Physician compliance with warfarin prophylaxis for central venous catheters in patients with solid tumors. J Clin Oncol 2000; 18: 3665-7.
• 16 Van Rooden CJ, Monraats PS, Kettenis IM. et al. Low physician compliance of prescribing anticoagulant prophylaxis in patients with solid tumor or hematological malignancies and central vein catheters. J Thromb Haemost 2003; 01: 1842-3.
• 17 Seldinger SI. Catheter replacement of the needle in percutaneous arteriography: a new technique. Acta Radiol 1953; 39: 368-76.
• 18 Mermel LA, Farr BM, Sheretz RJ. et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001; 32: 1249-72.
• 19 Girolami B, Prandoni P, Stefani PM. et al. The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood 2003; 101: 2955-9.
• 20 Koksoy C, Kuzu A, Kutlay J. et al. The diagnostic value of colour Doppler ultrasound in central venous catheter related thrombosis. Clin Radiol 1995; 50: 687-9.
• 21 Prandoni P, Polistena P, Bernardi E. et al. Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med 1997; 157: 57-62.
• 22 Patel MC, Berman LH, Moss HA. et al. Subclavian and internal jugular veins at Doppler US: abnormal cardiac pulsatility and respiratory phasicity as a predictor of complete central occlusion. Radiology 1999; 211: 579-83.
• 23 Bern MM, Lokich JJ, Wallach SR. et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med 1990; 112: 423-8.
• 24 Monreal M, Alastrue A, Rull M. et al. Upper extremity deep venous thrombosis in cancer patients with venous access devices: prophylaxis with a low molecular weight heparin (Fragmin). Thromb Haemost 1996; 75: 251-3.
• 25 Couban S, Goodyear M, Burnell M, Dolan S. A randomized double-blind placebo-controlled study of low dose warfarin for the prevention of symptomatic central venous catheter-associated thrombosis in patients with cancer [abstract]. Blood 2002; 100: 2769.
• 26 Reichart P, Kretzschmar A, Biakhov M. et al. A phase III double-blind, placebo-controlled study evaluating the efficacy and safety of daily low-molecular-weight heparin (dalteparin sodium, fragmin) in preventing catheterrelated complications in cancer patients with central venous catheters [abstract]. Proc Annu Meet Am Soc Clin Oncol 2002; 21: 1474.
• 27 Boraks P, Seale J, Price J. et al. Prevention of central catheter associated thrombosis using minidose warfarin in patients with haematological malignancies. Br J Haematol 1998; 101: 483-6.
• 28 Lagro SW, Verdonck LF, Borel IHRinkes. et al. No effect of nadroparin prophylaxis in the prevention of central venous catheter (CVC)associated thrombosis in bone marrow transplant recipients. Bone Marrow Transplant 2000; 26: 1103-6.
• 29 Attal M, Huguet F, Rubie H. et al. Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial. Blood 1992; 79: 2834-40.
• 30 Hentschel R, Wiescholek U, Lengerke J von. et al. Coagulation-associated complications of indwelling arterial and central venous catheters during heparin prophylaxis: a prospective study. Eur J Pediatr 1999; 158 (Suppl. 03) S126-129.
• 31 Warkentin TE, Levine MN, Hirsh J. et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330-5.
• 32 Warkentin TE, Sheppard JA, Horsewood P. et al. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 2000; 96: 1703-8.
• 33 Nowak-Gottl U, Dubbers A, Kececioglu D. et al. Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a prospective study. J Pediatr 1997; 131: 608-12.
• 34 Riordan M, Weiden PL. Factor V Leiden mutation does not account for central venous catheter-related thrombosis. Am J Hematol 1998; 58: 150-2.
• 35 Ruud E, Holmstrom H, Natvig S. et al. Prevalence of thrombophilia and central venous catheter-associated neck vein thrombosis in 41 children with cancer: a prospective study. Med Pediatr Oncol 2002; 38: 405-10.
• 36 Mitchell LG, Andrew M, Hanna K. et al. A prospective cohort determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line treated with L-asparaginase: results of the PARKAA study. Cancer 2003; 97: 508-16.
• 37 Fijnheer R, Paijmans B, Verdonck LF. et al. Factor V Leiden in central venous catheterassociated thrombosis. Br J Haematol 2002; 118: 267-70.
• 38 Van Rooden CJ, Rosendaal FR, Meiders AE. et al. The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter-related thrombosis. Haematologica 2004; 89: 201-6.
• 39 Van Rooden CJ, Rosendaal FR, Barge RM. et al. Central venous catheter related thrombosis in haematology patients and prediction of risk by screening with Doppler-ulrasound. Br J Haematol 2003; 123: 507-12.
• 40 Luciani A, Clement O, Halimi P. et al. Catheter-related upper extremity deep venous thrombosis in cancer patients: a prospective study based on Doppler US. Radiology 2001; 220: 655-60.
• 41 Cronan JJ. Contemporary venous imaging. Cardiovasc Intervent Radiol 1991; 14: 87-97.