目的 系统综述与分析万古霉素致血小板减少症的特点, 为临床实践提供证据及建议。方法 计算机检索PUBMED、EMBASE、CBM、CNKI、VIP和WANFANG数据库, 时间截至2017年1月, 纳入万古霉素致血小板减少症的中英文病例报道, 两位研究者独立文献筛选与资料提取、统计。结果 共检出文献2 428篇, 最终纳入36篇, 37位患者。70.3%患者为男性, 中位年龄55.0岁, 大多存在基础疾病, 合用多种药物, 62.2%患者联用抗菌药物。ADR表现为血小板减少或全血细胞减少伴或不伴出血症状, 45.9%患者存在严重出血症状。首次和再次出现ADR的中位时间为7.0 d和24.0 h, 中位累积药量为8.0 g和3.5 g, 中位血小板计数为23.0×109个L-1和77.0×109个L-1;首次和再次出现最低血小板计数的中位时间为9.0 d和24.0 h, 中位累积药量为16.0 g和3.5 g, 中位血小板计数为10.0×109个L-1和58.0×109个L-1;血小板计数恢复正常的中位时间为5.0 d和4.5 d。1例患者第3次用单剂1 g万古霉素12 h即出现最低血小板计数11.0×109个L-1, 停药7.0 d恢复正常。94.6%患者停药或联合其他措施后血小板计数均恢复正常, 3例患者最终死亡, 但均不是万古霉素ADR导致。59.5%患者检测了万古霉素依赖性血小板抗体。ADR关联性评价为肯定有关4例, 很可能有关23例, 可能有关10例。结论 万古霉素致血小板减少症需引起临床的关注, 中老年男性患者、合并基础疾病、肾功能不全、应用影响血小板的药物及给药疗程长等可能为高危因素, 建议密切监测血小板计数。药物依赖性抗体的测定有助于确定血小板减少的原因, 其发生率及严重性还需要更多的数据进一步证实。
Abstract
OBJECTIVE To review and analyze the clinical characteristics of thrombocytopenia induced by vancomycin. METHODS Databases of PUBMED、EMBASE、CBM、CNKI、VIP and WANFANG data (from built to January 2017) were conducted for case reports published in English or Chinese involving thrombocytopenia induced by vancomycin. Literatures were screened, extracted and statistics analysis by two authors independently. RESULTS A total of 2 428 literatures were searched out and 36 were included involving 37 patients. 70.3% of the patients were male, median age was 55.0 years, most of them had underlying diseases and combined with a variety of drugs, 62.2% of which combined with other antimicrobial agents.The clinical manifestation of ADR was thrombocytopenia or complete blood loss associated with or without bleeding symptoms, 45.9% patients were attacted by severe bleeding.The median time of thrombocytopenia for the first and second time was 7.0 d and 24.0 h, the median cumulative dosage was 8.0 g and 3.5 g, the median platelet counts was 23.0×109L-1 and 77.0×109L-1, respectively. The median time to platelet nadir counts for the first and second time was 9.0 d and 24.0 h, the median cumulative dosage was 16.0 g and 3.5 g, the median platelet counts was 10.0×109L-1 and 58.0×109L-1, respectively. The median time returned to normal platelet counts for the first and second time was 5.0 d and 4.5 d, respectively.For the third time, a single dose of vancomycin was administered and thrombocytopenia developed within 12 h with a nadir platelet counts of 11.0×109L-1, the platelet counts restored to normal within 7.0 d. Platelet counts returned to normal in 94.6% of patients after vancomycin was discontinued and/or took other measures, three of them died from various reasons but not the ADR of vancomycin. Vancomycin-dependent antibodies were detected in 59.5% of patients. The correlation evaluation of ADR was definite, probable, and possible in 4, 23, and 10 patients, respectively.CONCLUSION High attention should be put on thrombocytopenia induced by vancomycin, male patients with middle or old age, underlying diseases, renal insufficiency and exposure to drugs were the risk factors of thrombocytopenia .Platelet counts should be closely monitored during the use of vancomycin. Testing for drug-dependent antibodies can be helpful for identifying the cause of thrombocytopenia in patients who were receiving vancomycin. More data is need to confirm the incidence and severity of thrombocytopenia induced by vancomycin.
关键词
万古霉素 /
血小板减少症 /
不良反应 /
系统回顾性分析
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Key words
vancomycin /
thrombocytopenia /
adverse drug reaction /
systematic retrospective study
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