Groote Schuur Hospital, Cape Town.
S Afr Med J. 2010 Jun 1;100(6):372-7. doi: 10.7196/samj.3565.
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).
We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa.
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/microl, 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 beta-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.
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.
在世纪之交，仅报道了 300 例华法林诱导的皮肤坏死（WISN）病例。WISN 是华法林治疗的一种罕见但潜在致命的并发症。尚无关于 HIV-1 感染或结核病（TB）患者发生 WISN 的报道。
我们回顾了 2005 年 4 月至 2008 年 7 月在南非开普敦一家转诊医院就诊的接受华法林治疗的静脉血栓形成患者中发生的 WISN 病例。
在接受华法林治疗静脉血栓形成的 973 例患者中，有 6 例发生 WISN（0.62%，95%CI 0.25-1.37%）。所有 6 例均发生在 HIV-1 感染的女性（中位年龄 30 岁，范围 27-42 岁），均伴有微生物学确诊的结核病和静脉血栓形成。所有患者均严重免疫抑制（TB 诊断时的中位 CD4+计数为 49 个/μl，四分位间距为 23-170）。在接受联合抗逆转录病毒治疗的 3 例患者中，有 2 例出现结核-IRIS（免疫重建炎症综合征）。从开始抗结核治疗到发生静脉血栓形成的中位间隔时间为 37 天（范围 0-150 天）。同时使用肝素和华法林治疗的中位时间为 2 天（范围 1-6 天）。WISN 在开始华法林治疗后 6 天（范围 4-8 天）出现。WISN 发作时的国际标准化比值（INR）高于治疗范围，中位数为 6.2（范围 3.8-6.6）。WISN 的部位包括乳房、臀部和大腿。在 WISN 发作后 17-37 天，有 4 例中的 6 例 WISN 部位继发感染了耐多药医院获得性细菌（耐甲氧西林金黄色葡萄球菌（MRSA）、不动杆菌、产超广谱β-内酰胺酶（ESBL）的大肠杆菌和肺炎克雷伯菌）。在 4 例患者中，从 WISN 发作到死亡的中位间隔时间为 43 天（范围 25-45 天）。在存活的 2 例患者中，有 1 例在专科中心接受了双侧乳房切除术和广泛植皮。
这是 WISN 最大的病例系列之一。我们报告了一种新的临床实体：HIV-1 感染合并结核病和静脉血栓形成患者的 WISN。在 40 个月的时间里，有 6 例 WISN 病例发生，可能归因于（i）HIV-1 和结核病导致的高凝状态：（ii）同时使用肝素和华法林治疗时间短；和（iii）华法林的高负荷剂量。积极预防和适当治疗 WISN 可能会改善这种不常见疾病的严重发病率和死亡率。
