Utilisation and Safety of Low Molecular Weight Heparins
Utilisation and Safety of Low Molecular Weight Heparins
复制标题
低分子肝素的利用和安全性
作者：
P. Cestac;H. Bagheri;M. Lapeyre;P. Sié;A. Fouladi;E. Maupas;P. Léger;B. Fontan;P. Massip;J. Montastruc
摘要目的：低分子量肝素（LMWH）被广泛用于治疗或预防血栓栓塞性疾病。我们研究的目的是：（i）调查法国教学医院不同科室的低分子量肝素处方模式;（ii）估计低分子量肝素诱导的药物不良反应（ADR）发生率和出血事件发生的相关风险因素。
方法：这项前瞻性研究于1999年3月在图卢兹（法国西南部）的两家教学医院的不同内科病房进行。所有接受LMWH处方的患者均纳入调查。所有数据均在每个病房前瞻性记录。
结果：共纳入334例患者。性别比（男性/女性）为1.25，平均年龄为72.5 ± 16.3岁（极端年龄：18-101岁）。共收集了450张低分子肝素处方（每例患者1.34张处方），主要涉及依诺肝素（61%），在75岁以上的患者中，依诺肝素的使用频率高于汀扎肝素（71.7% vs 28.3%; p < 0.0001）。99例患者接受了LMWH治疗（对应于127张处方，其中99张为依诺肝素，28张为亭扎肝素[p < 0.0001]）。适应症包括治疗深静脉血栓形成、肺栓塞、急性冠脉综合征、不稳定型心绞痛、非Q波心肌梗死。严重肾功能不全在老年科患者中明显更常见（p < 0.00001）。严重或中度肾功能不全患者使用依诺肝素的频率高于汀扎肝素（72% vs 61%，p < 0.05）。下肢深静脉血栓预防性治疗中发生不良反应22例，发生率为10.5%，治疗性治疗中发生不良反应13例。11例病例（31.4%）的ADR被归类为“严重”。报告的ADR为出血事件（n = 15）、血小板增多（n = 13）、血小板减少（n = 4）和肝细胞溶解（n = 1）。出血效应发生的平均延迟时间为8.0 ± 9.1天（范围1-40）。多变量分析几个标准对出血效应发生的影响显示，肌酐清除率降低（10 ml/min）与出血风险增加相关（相对风险[RR] = 1.34，95% CI 1.12-1.65; p < 0.05）。此外，肌酐清除率<20 ml/min的患者发生不良出血反应的风险增加（RR = 2.8; 95% CI 1.00-7.8）。
结论：我们的数据首次显示了不同临床病房低分子肝素处方的不同模式。其次，对于所研究的两种LMWH制剂，接受LMWH治疗的患者中出血ADR的风险随着肾功能损害而显著增加。有必要在有几个风险因素的患者中进行更多的药物流行病学研究，特别是在经常有肾损害的老年人中，以确定每种LMWH的最佳使用模式。
AbstractAims: Low molecular weight heparins (LMWHs) are widely used as curative or preventive treatments of thromboembolic diseases. The aim of our study was to: (i) investigate the pattern of prescription of LMWHs in different departments of French teaching hospitals; and (ii) estimate the incidence of adverse drug reactions (ADRs) induced by LMWHs and associated risk factors for the occurrence of bleeding events.
Methods: This prospective study was performed in two teaching hospitals in Toulouse (south-western France) in March 1999 in different medical wards. All patients receiving a prescription for a LMWH were included in the survey. All data were prospectively recorded in each ward.
Results: A total of 334 patients were included. Sex ratio (male/female) was 1.25 and mean age was 72.5 ± 16.3 years (extremes: 18–101). 450 prescriptions for LMWHs were collected (1.34 prescription per patient) and involved mainly enoxaparin (61%), which was more frequently used than tinzaparin in patients over 75 years old (71.7 vs 28.3%; p < 0.0001). Ninety-nine patients received a LMWH for curative treatment (corresponding to 127 prescriptions of which 99 were for enoxaparin and 28 were for tinzaparin [p < 0.0001]). Indications included therapy for deep venous thrombosis, pulmonary embolism, acute coronary syndrome, unstable angina pectoris, non-Q-wave myocardial infarction. Serious renal insufficiency was significantly more frequent in patients from the geriatrics department (p < 0.00001). Enoxaparin was prescribed more frequently in patients with serious or moderate renal insufficiency than tinzaparin (72 vs 61%, p < 0.05). The incidence of LMWHs-induced ADRs was 10.5% occurring in 22 cases during preventive treatment of deep venous thrombosis and in 13 cases during curative therapy. ADRs were classified as ‘serious’ in 11 cases (31.4%). Reported ADRs were bleeding events (n = 15), thrombocytosis (n = 13), thrombopenia (n = 4) and hepatic cytolysis (n = 1). The mean delay for the occurrence of bleeding effects was 8.0 ± 9.1 days (range 1–40). Multivariate analysis of the influence of several criteria on the occurrence of haemorrhagic effects showed that the decrease of creatinine clearance (10 ml/min) was associated with an increased haemorrhagic risk (relative risk [RR] = 1.34, 95% CI 1.12–1.65; p < 0.05). Moreover, the risk of adverse bleeding effects increased for patients with a creatinine clearance <20 ml/min (RR = 2.8; 95% CI 1.00–7.8).
Conclusion: Our data firstly show a different pattern of LMWHs prescription in different clinical wards. Secondly, the risk of bleeding ADRs in patients treated by LMWHs increases significantly with renal function impairment for the two LMWH preparations studied. More pharmacoepidemiological studies are necessary in patients with several risk factors, particularly in elderly people who often have renal impairment, in order to determine the optimal pattern use of each LMWH.
影响因子：
5.9
作者：
White, RH;Beyth, RJ;Romano, PS
通讯作者：
Romano, PS