Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search    Get Permissions  Google Scholar    Search for Related Content  Social Bookmarking

What's this?

PubMed

Articles in PubMed by Author:    Warkentin, T. E.    Related Articles in PubMed    PubMed Citation    PubMed

BRIEF COMMUNICATION

Venous Limb Gangrene during Warfarin Treatment of Cancer-Associated Deep Venous Thrombosis

Theodore E. Warkentin, MD

16 October 2001 | Volume 135 Issue 8 Part 1 | Pages 589-593

Background: The cause of cancer-associated venous limb gangrene is unknown but could paradoxically be due to warfarin.

Objective: To determine the pathogenesis of venous gangrene in a patient with cancer.

Design: Case report.

Setting: University hospital in Ontario, Canada.

Patient: 66-year-old woman with metastatic lung cancer and deep venous thrombosis.

Measurements: Levels of vitamin K–dependent factors, additional coagulation factors, and thrombin–antithrombin complexes (marker of thrombin generation).

Results: During warfarin use, venous limb gangrene developed when the international normalized ratio (INR) reached 6.0 (therapeutic range, 2.0 to 3.0); at this time, the level of protein C (a vitamin K–dependent natural anticoagulant) was severely reduced, but thrombin–antithrombin complexes remained markedly elevated. The supratherapeutic INR was explained by the greatly reduced levels of factor VII, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity.

Conclusion: Warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein C while at the same time failing to reduce thrombin generation.

Author and Article Information

From McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

Acknowledgments: The author thanks Professor Jim Julian for assistance with statistical calculations, Drs. Jack Hirsh and Frederick A. Ofosu for helpful discussions, and Marilyn Johnston, Jo-Ann I. Sheppard, and Patti Simpson for performing the coagulation studies.

Grant Support: By the Heart and Stroke Foundation of Ontario (grant-in-aid #T-2967).

Requests for Single Reprints: Theodore E. Warkentin, MD, Hamilton General Hospital, Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

Related articles in Annals:

Summaries for Patients
Gangrene of the Leg during Warfarin Treatment in a Patient with Cancer

Annals 2001 135: S49. [Full Text]  

This article has been cited by other articles:

				J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, and G. Palareti Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 160S - 198S. [Abstract] [Full Text] [PDF]

				T. E. Warkentin, A. Greinacher, A. Koster, and A. M. Lincoff Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 340S - 380S. [Abstract] [Full Text] [PDF]

				J. R. Bartholomew Transition to an Oral Anticoagulant in Patients With Heparin-Induced Thrombocytopenia Chest, February 1, 2005; 127(2_suppl): 27S - 34S. [Abstract] [Full Text] [PDF]

				W. E Dager, T. G Vondracek, B. A McIntosh, and E. A Nutescu Ximelagatran: An Oral Direct Thrombin Inhibitor Ann. Pharmacother., November 1, 2004; 38(11): 1881 - 1897. [Abstract] [Full Text] [PDF]

				M. A. Smythe, W. E. Dager, and N. M. Patel Managing Complications of Anticoagulant Therapy Journal of Pharmacy Practice, October 1, 2004; 17(5): 327 - 346. [Abstract] [PDF]

				J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobson, and E. Hylek The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 204S - 233S. [Abstract] [Full Text] [PDF]

				T. E. Warkentin and A. Greinacher Heparin-Induced Thrombocytopenia: Recognition, Treatment, and Prevention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 311S - 337S. [Abstract] [Full Text] [PDF]

				A. F. Srinivasan, L. Rice, J. R. Bartholomew, C. Rangaswamy, L. La Perna, J. E. Thompson, S. Murphy, and K. R. Baker Warfarin-Induced Skin Necrosis and Venous Limb Gangrene in the Setting of Heparin-Induced Thrombocytopenia Arch Intern Med, January 12, 2004; 164(1): 66 - 70. [Abstract] [Full Text] [PDF]

				S. Georgin, J. Pouchot, F. Raschilas, S. Barete, D. L. Lerolle, and P. Vinceneux Paradoxical Venous Limb Gangrene Complicating Oral Anticoagulation in a Patient With Cancer-Associated Deep Venous Thrombosis Arch Dermatol, September 1, 2003; 139(9): 1126 - 1128. [Full Text] [PDF]

				T. E. Warkentin, W. C. Aird, and J. H. Rand Platelet-Endothelial Interactions: Sepsis, HIT, and Antiphospholipid Syndrome Hematology, January 1, 2003; 2003(1): 497 - 519. [Abstract] [Full Text] [PDF]