Original articles

Warfarin-induced skin necrosis in HIV-1-infected patients with tuberculosis and venous thrombosis

F Bhaijee, H Wainwright, G Meintjes, R J Wilkinson, G Todd, E de Vries, D J Pepper

Abstract


Background. At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB).
Methods. We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa.
Results. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/µl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre.
Conclusion. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB: (ii) short concurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition.

Authors' affiliations

F Bhaijee, Groote Schuur Hospital, Anzio Road, Observatory 7925

H Wainwright, Department of Pathology, Division of Anatomical Pathology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925

G Meintjes, Institute of Infectious Diseases and Molecular Medicine, and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925; Infectious Diseases Unit, GF Jooste Hospital, Manenberg 7764

R J Wilkinson, Institute of Infectious Diseases and Molecular Medicine, and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925; Infectious Diseases Unit, GF Jooste Hospital, Manenberg 7764

G Todd, Department of Dermatology, Groote Schuur Hospital and University of Cape Town, Anzio Road, Observatory 7925

E de Vries, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory 7925

D J Pepper, Institute of Infectious Diseases and Molecular Medicine, and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925; Infectious Diseases Unit, GF Jooste Hospital, Manenberg 7764

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Keywords

HIV; tuberculosis; thrombosis; warfarin; warfarin induced skin necrosis; tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS)

Cite this article

South African Medical Journal 2010;100(6):372-377.

Article History

Date submitted: 2009-06-09
Date published: 2010-06-01

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