Thromb Haemost 2008; 99(01): 38-43
DOI: 10.1160/TH07-07-0446
Review Article
Schattauer GmbH

Thromboprophylaxis in cancer patients with central venous catheters

A systematic review and meta-analysis
Pooja Chaukiyal
1   Department of Medicine, Unity Health System, Rochester, New York, USA
,
Amit Nautiyal
2   Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
,
Sangeetha Radhakrishnan
3   PSG Medical College, Coimbatore, India
,
Sonal Singh
4   Department of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA
,
Sankar D Navaneethan
5   Division of Nephrology, University of Rochester, Rochester, New York, USA
› Author Affiliations
Further Information

Correspondence to:

Pooja Chaukiyal, MD
Department of Medicine, Unity Health system
1555 Long Pond Road, Rochester, NY 14626, USA
Phone: +1 585 224 5981   
Fax: +1 585 723 7834   

Publication History

Received: 10 July 2007

Accepted after major revision: 07 October 2007

Publication Date:
24 November 2017 (online)

 

Summary

It was the aim of the review to determine the risks and benefits of primary thromboprophylaxis with anticoagulants in cancer patients with central venous devices. Medline, Central and Google Scholar databases were searched for randomized controlled trials (RCTs) in June 2006.Two reviewers extracted data and appraised the quality of RCTs. Results were expressed as relative risk (RR) with 95% confidence intervals (CI) using random effects model for the outcomes of catheter-related thrombosis, bleeding and thrombocytopenia. Eight RCTs (1,428 patients) were included. There was no statistically significant difference in the risk of catheter-related thrombosis for the use of warfarin versus placebo (3 trials, 425 patients, RR 0.75, 95% CI 0.24–2.35,p=0.63),heparin versus placebo (4 trials,886 patients, RR 0.46 95% CI 0.18–1.20, p=0.06) or warfarin, unfractionated heparin or low-molecular-weight heparin versus placebo (7 trials, 1,311 patients, RR 0.59, 95% CI 0.31–1.13, p=0.11). Substantial statistical heterogeneity was noted among these trials (I2>50%).The use of anticoagulants showed no statistically significant difference in the risk of overall bleeding (5 trials, 1,193 patients, RR 1.24, 95% CI 0.84–1.82, p=0.28), and thrombocytopenia for heparin versus placebo (4 trials, 958 patients, RR 0.85, 95% CI 0.49, 1.46, p=0.55) without any statistical heterogeneity (I2=0%). In cancer patients with central venous devices, thromboprophylaxis has no significant effect on the risk of catheter related thrombosis or bleeding. The use of primary thromboprophylaxis in cancer patients with central venous catheters while not causing any harm provides no benefit.


#

 


#
  • References

  • 1 Kuter DJ. Thrombotic complications of central venous catheters in cancer patients. Oncologist 2004; 9: 207-216.
  • 2 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: 251-253.
  • 3 Cunningham MS, White B, Hollywood D. et al. Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence. Br J Cancer 2006; 94: 189-194.
  • 4 Cushman M, Tsai AW, White RH. et al. Deep venous thrombosis and pulmonary embolism in two cohorts: The longitudinal investigation of thromboembolism etiology. Am J Med 2004; 17: 19-25.
  • 5 Anderson AJ, Krasnow SH, Boyer MW. et al. Thrombosis: the major Hickman catheter complication in patients with solid tumor. Chest 1989; 95: 71-75.
  • 6 Hill SL, Berry RE. Subclavian vein thrombosis: A continuing challenge. Surgery 1990; 108: 1-9.
  • 7 Wechsler RJ, Spim PW, Conant EF. et al. Thrombosis and infection caused by thoracic venous catheters: Pathogenesis and imaging findings. AJR Am J Roentgenol 1993; 160: 467-471.
  • 8 Thodiyil PA, Kakkar AK. Variation of relative risk of venous thromboembolism in different cancers. Thromb Haemost 2002; 87: 1076-1077.
  • 9 Eastman ME, Khorsand M, Maki DG. et al. Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2. Cancer 2001; 91: 806-814.
  • 10 Geerts WH, Pineo GF, Heit JA. et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 338-400.
  • 11 Schulz KF, Chalmers I, Hayes RJ. et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. J Am Med Assoc 1995; 273: 408-412.
  • 12 Bern MM, Lokich JJ, Wallach SR. et al. Very low dose warfarin can prevent thrombosis in central venous catheters. Ann Intern Med 1990; 112: 423-428.
  • 13 Couban S, Goodyear M, Burnell M. et al. Randomized Placebo Controlled study of low dose warfarin for prevention of central venous catheter associated thrombosis in patients with cancer. J Clin Oncol 2005; 23: 4063-4068.
  • 14 Heaton D, Han DY, Inder A. Mini dose (1 mg) warfarin as prophylaxis for central venous catheter thrombosis. Intern Med J 2002; 32: 84-88.
  • 15 Karthaus M, Kretzschmar A, Kroning H. Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double blind, placebo-controlled phase III trial. Ann Oncol 2006; 17: 289-296.
  • 16 Abdelkefi A, Ben Othman T, Kammoun L. et al. Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial. Thromb Haemost 2004; 92: 654-661.
  • 17 Verso M, Agnelli G, Bertoglio S, Di Somma FC, Paoletti F, Ageno V. et al: Enoxaparin for prevention of venous thromboembolism associated with central vein catheter: A double blind, Placebo controlled Randomized studying cancer patients. J Clin Oncol 2005; 23: 4057-62.
  • 18 Mismetti P, Mille D, Laporte S, Charlet V, Buchmuller-Cordier A, Jacquin JP. et al: Low-molecularweight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial. Haematologica 2003; 88: 67-73.
  • 19 Randolph AG, Cook DJ, Gonzales CA. et al. Benefit of heparin in central venous and pulmonary artery catheters. A metaanalysis of Randomized control trials; Chest 1998; 113: 165-171.
  • 20 Klerk CP, Smorenburg SM, Buller HR. Thrombosis prophylaxis in patient populations with central venous catheters. Arch Intern Med 2003; 163: 1913-1921.
  • 21 Cicco De, Matovic M, Balestreri L. et al. Anti thrombin III deficiency as a risk factor for catheter related central venous thrombosis. Thromb Res 1995; 78: 127-137.
  • 22 Massicotte P, Julian JA, Gent M. et al. An open label randomized control trial of low molecular weight heparin of central venous line related thrombotic complications in children: The PROTEKT trial. Thromb Res 2003; 109: 101-108.
  • 23 Boraks P, Seale J, Price J. et al. Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with hematological malignancy. Br J Haematol 1998; 101: 483-486.
  • 24 Ratcliffe M, Broadfoot C, Davidson M. et al. Thrombosis, markers of thrombotic risk, indwelling central venous catheters and thrombotic prophylaxis using low dose warfarin in subjects with malignant disease. Clin Lab Haematol 1999; 21: 353-57.
  • 25 Levine M, Kakkar AK. Catheter associated thrombosis: Thromboprophylaxis or not?. J Clin Oncol 2005; 23: 4006-4008.
  • 26 Lee AY, Levine MN, Butler G. et al. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol 2006; 24: 1404-1408.
  • 27 Kuderer NM, Khorana AA, Lyman GH. et al. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment : impact on survival and bleeding complications. Cancer. 2007 epub ahead of print.
  • 28 Weitz JI. Emerging anticoagulants for the treatment of venous thromboembolism. Thromb Haemost 2006; 96: 274-284.
  • 29 Becattini C, Agnelli G, Emmerich J. et al. Initial treatment of venous thromboembolism. Thromb Haemost 2006; 96: 42-50.
  • 30 Ng HJ, Crowther MA. Malignancy-associated venous thrombosis with concurrent warfarin-induced skin necrosis, venous limb gangrene and thrombotic microangiopathy. Thromb Haemost 2006; 95: 1038-1039.

Correspondence to:

Pooja Chaukiyal, MD
Department of Medicine, Unity Health system
1555 Long Pond Road, Rochester, NY 14626, USA
Phone: +1 585 224 5981   
Fax: +1 585 723 7834   

  • References

  • 1 Kuter DJ. Thrombotic complications of central venous catheters in cancer patients. Oncologist 2004; 9: 207-216.
  • 2 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: 251-253.
  • 3 Cunningham MS, White B, Hollywood D. et al. Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence. Br J Cancer 2006; 94: 189-194.
  • 4 Cushman M, Tsai AW, White RH. et al. Deep venous thrombosis and pulmonary embolism in two cohorts: The longitudinal investigation of thromboembolism etiology. Am J Med 2004; 17: 19-25.
  • 5 Anderson AJ, Krasnow SH, Boyer MW. et al. Thrombosis: the major Hickman catheter complication in patients with solid tumor. Chest 1989; 95: 71-75.
  • 6 Hill SL, Berry RE. Subclavian vein thrombosis: A continuing challenge. Surgery 1990; 108: 1-9.
  • 7 Wechsler RJ, Spim PW, Conant EF. et al. Thrombosis and infection caused by thoracic venous catheters: Pathogenesis and imaging findings. AJR Am J Roentgenol 1993; 160: 467-471.
  • 8 Thodiyil PA, Kakkar AK. Variation of relative risk of venous thromboembolism in different cancers. Thromb Haemost 2002; 87: 1076-1077.
  • 9 Eastman ME, Khorsand M, Maki DG. et al. Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2. Cancer 2001; 91: 806-814.
  • 10 Geerts WH, Pineo GF, Heit JA. et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 338-400.
  • 11 Schulz KF, Chalmers I, Hayes RJ. et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. J Am Med Assoc 1995; 273: 408-412.
  • 12 Bern MM, Lokich JJ, Wallach SR. et al. Very low dose warfarin can prevent thrombosis in central venous catheters. Ann Intern Med 1990; 112: 423-428.
  • 13 Couban S, Goodyear M, Burnell M. et al. Randomized Placebo Controlled study of low dose warfarin for prevention of central venous catheter associated thrombosis in patients with cancer. J Clin Oncol 2005; 23: 4063-4068.
  • 14 Heaton D, Han DY, Inder A. Mini dose (1 mg) warfarin as prophylaxis for central venous catheter thrombosis. Intern Med J 2002; 32: 84-88.
  • 15 Karthaus M, Kretzschmar A, Kroning H. Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double blind, placebo-controlled phase III trial. Ann Oncol 2006; 17: 289-296.
  • 16 Abdelkefi A, Ben Othman T, Kammoun L. et al. Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial. Thromb Haemost 2004; 92: 654-661.
  • 17 Verso M, Agnelli G, Bertoglio S, Di Somma FC, Paoletti F, Ageno V. et al: Enoxaparin for prevention of venous thromboembolism associated with central vein catheter: A double blind, Placebo controlled Randomized studying cancer patients. J Clin Oncol 2005; 23: 4057-62.
  • 18 Mismetti P, Mille D, Laporte S, Charlet V, Buchmuller-Cordier A, Jacquin JP. et al: Low-molecularweight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial. Haematologica 2003; 88: 67-73.
  • 19 Randolph AG, Cook DJ, Gonzales CA. et al. Benefit of heparin in central venous and pulmonary artery catheters. A metaanalysis of Randomized control trials; Chest 1998; 113: 165-171.
  • 20 Klerk CP, Smorenburg SM, Buller HR. Thrombosis prophylaxis in patient populations with central venous catheters. Arch Intern Med 2003; 163: 1913-1921.
  • 21 Cicco De, Matovic M, Balestreri L. et al. Anti thrombin III deficiency as a risk factor for catheter related central venous thrombosis. Thromb Res 1995; 78: 127-137.
  • 22 Massicotte P, Julian JA, Gent M. et al. An open label randomized control trial of low molecular weight heparin of central venous line related thrombotic complications in children: The PROTEKT trial. Thromb Res 2003; 109: 101-108.
  • 23 Boraks P, Seale J, Price J. et al. Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with hematological malignancy. Br J Haematol 1998; 101: 483-486.
  • 24 Ratcliffe M, Broadfoot C, Davidson M. et al. Thrombosis, markers of thrombotic risk, indwelling central venous catheters and thrombotic prophylaxis using low dose warfarin in subjects with malignant disease. Clin Lab Haematol 1999; 21: 353-57.
  • 25 Levine M, Kakkar AK. Catheter associated thrombosis: Thromboprophylaxis or not?. J Clin Oncol 2005; 23: 4006-4008.
  • 26 Lee AY, Levine MN, Butler G. et al. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol 2006; 24: 1404-1408.
  • 27 Kuderer NM, Khorana AA, Lyman GH. et al. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment : impact on survival and bleeding complications. Cancer. 2007 epub ahead of print.
  • 28 Weitz JI. Emerging anticoagulants for the treatment of venous thromboembolism. Thromb Haemost 2006; 96: 274-284.
  • 29 Becattini C, Agnelli G, Emmerich J. et al. Initial treatment of venous thromboembolism. Thromb Haemost 2006; 96: 42-50.
  • 30 Ng HJ, Crowther MA. Malignancy-associated venous thrombosis with concurrent warfarin-induced skin necrosis, venous limb gangrene and thrombotic microangiopathy. Thromb Haemost 2006; 95: 1038-1039.