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Clinical Review ABC of antithrombotic therapy

Bleeding risks of antithrombotic therapy

BMJ 2002; 325 doi: (Published 12 October 2002) Cite this as: BMJ 2002;325:828

Cancer as risk factor for bleeding during Warfarin treatment

Dear Editor,

We read with great interest the excellent review by Fitzmaurice et al.
entitled Bleeding risks of antithrombotic therapy.
Among risk factors for bleeding cancer is an important issue to consider.

The estimated risk of major bleeding with warfarin therapy ranges from 0.2
to 5.2% [1,2], but there is controversy about whether patients with cancer
are at increased risk of recurrences and bleeding complications during
anticoagulant therapy. Several investigators have observed an increased
risk of haemorrhagic and thrombotic complications in cancer patients [3,
4]. In a recent retrospective analysis of two prospective studies [5, 6],
Hutten et al. [7] found that the risk for recurrence and major bleeding in
cancer patients was three- to six-fold that of patients without malignancy
during treatment with warfarin for VTE. These findings are consistent with
the results of Gitter et al. [8], who reported that malignant disease at
initiation of warfarin therapy is significantly associated with an
increased risk for major bleeding and recurrent.

In addition, the routine use of anticoagulant therapy during continuous
infusion of 5-fluorouracil is theoretically hampered by a potential
interaction between warfarin and this drug. Prolonged 5-fluorouracil half-
life and increased INR were reported, probably due to interference with
the synthesis of hepatic cytocrome 450 and impaired metabolism of warfarin
and 5-fluorouracil (9,10).


1. Levine M, Raskob G, Landefeld CS, Kearon C. Hemorrhagic complications
of anticoagulant treatment. Chest 1998;114:511-523.

2. Krauth D, Holden A, Knapic N, et al. Safety and efficacy of long-term
oral anticoagulation in cancer patients. Cancer 1987;59:983-985.

3. Moore FD, Osteen RT, Karp DD, et al. Anticoagulants, venous
thromboembolism, and the cancer patient. Arch Surg 1981;116:405-407.

4. Prandoni P. Antithrombotic strategies in patients with cancer. Thromb
Haemostas 1997;78:141-144.

5. Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous
thrombosis with intravenous unfractionated heparin administered in the
hospital as compared with subcutaneous low molecular weight heparin
administered at home. N Engl J Med 1996;334:682-687.

6. The Columbus Investigators. Low molecular weight heparin in the
treatment of patients with venous thromboembolism. N Engl J Med

7. Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen J, Buller HR.
Incidence of recurrent thromboembolic and bleeding complications among
patients with venous thromboembolism in relation to both malignancy and
achieved international normalised ratio. J Clin Oncol 2000;18:3078-3083.

8. Gitter MJ, Jaeger TM, Petterson TM, et al. Bleeding and thromboembolism
during anticoagulant therapy: A population-based study in Rochester,
Minnesota. Mayo Clin Proc 1995;70:725-733.

9. An adverse interaction between warfarin and 5-fluoruracil: A case
report and review of the literature. Chemotherapy 1999; 45: 392-395.

10. Scarfe MA, Israel MK. Possible drug interaction between warfarin and
combination of levamisole and fluoruracil. Ann Pharmacother 1994; 28:464

Competing interests: No competing interests

15 October 2002
Mario Mandala
Clinica Assistant
Marco Cremonesi, Marina Cazzaniga and Sandro Barni
Ospedale Treviglio Division of Medical Oncology P.le Ospedale 1 24047 Treviglio (Bg) Italy