头孢菌素是临床上常用的一类广谱抗生素 ,随着头孢菌素的广泛使用 ,少数患者可出现血液系统毒性反应。头孢菌素可诱发免疫性溶血性贫血 ,也可仅表现为Coombs实验阳性而无溶血的证据。在个别病例中 ,头孢菌素可通过免疫机制导致白细胞减少甚至粒细胞缺乏 ,但大量临床资料表明 :第三、四代头孢菌素用于粒细胞缺乏病人发热的治疗是安全的。凝血功能障碍和出血是头孢菌素的血液学毒性反应中最严重的 ,主要由于干扰了维生素K的代谢引起低凝血酶原血症和依赖维生素K的凝血因子活性降低 ,同时还可抑制血小板聚集 ,尤其是含有N MTZ结构的头孢菌素 ,表现尤为突出。了解头孢菌素的血液学毒性反应有利于临床医生合理用药 ,

药源性疾病是一个全球性的问题,它约占药物不良反应总病例数的10%左右,占药物相关死亡病例的40%[1].许多药物可引起凝血、止血障碍,虽然发生率不高,但是药物相关的出血可危及生命.如果不进行相关监测,常无先兆的出血可导致严重后果.

A bleeding diathesis characterized by in-vitro platelet dysfunction and prolongation of the template bleeding time (TBT) has been reported in patients receiving latamoxef ('moxalactam'), but not cefotaxime or cefoperazone. Hypoprothrombinaemia has been associated with the use of both latamoxef and cefoperazone in seriously ill and malnourished patients. We administered either latamoxef, cefotaxime or cefoperazone intravenously, at dosages within the range recommended by each manufacturer, to 14 normal volunteers. Latamoxef caused a dose and time dependent defect in platelet function characterized in vitro by abnormalities in aggregation to adenosine diphosphate and in vivo by prolongation of the template bleeding time. In two out of two subjects, a single 4 g dose of latamoxef caused neither prolongation of template bleeding times nor aggregation abnormalities. Two out of two subjects receiving latamoxef 6 g/day for six days had progressive prolongation of bleeding times to 12 and 15 min. Two additional subjects receiving latamoxef 12 g/day for four days had prolongation of template bleeding times to greater than 20 min. Of four subjects receiving cefotaxime 12 g/day for seven days, none had prolongation of template bleeding times or abnormalities in platelet aggregations. Of four subjects receiving cefoperazone 6 g/day, none had significant prolongation of template bleeding times and one had abnormalities in aggregation attributed to inadvertent salicylate ingestion. Prolongation of the prothrombin time or activated partial thromboplastin time did not occur in any of the 14 volunteers. Latamoxef is more likely to interfere with platelet function than either cefotaxime or cefoperazone.

患者男,75岁,因“咳嗽、咳痰2个月,发热1周”入院,诊断:两肺感 染.入院时查血常规:WBC 11.2×109/L,N％ 82.5％,L％ 16.6％,Hb 112 g/L,PLT 274×109/L.凝血常规:PT 13 s,PT活动度78％,INR 1.11,APTT 36.1 s,TT19.8 s,FIB 3.33 g/L.因患者院外已使用阿莫西林舒巴坦3.0静滴bid联合左氧氟沙星0.4静滴qd抗感染4d,但疗效差.故入院后换为拉氧头孢(商品名:噻吗灵,海 南海灵制药厂有限公司)1.0静滴bid抗感染,氨溴索化痰,吉诺通胶囊祛痰,多索茶碱解痉平喘及雾化等治疗.用药后患者体温降至正常,咳嗽、咳痰及两肺 干湿啰音明显减少,病情好转.用药第3天复查血常规:WBC 9.4×109/L,N％ 78.6％,L％21.2％,Hb 108 g/L,PLT 186×109/L.