Division of Hematology and Central Hematology Laboratory, Department of Medicine, Luzerner Kantonsspital, CH-6000 Luzern 16, Switzerland.
J Thromb Haemost. 2009 Oct;7(10):1629-32. doi: 10.1111/j.1538-7836.2009.03556.x. Epub 2009 Jul 17.
Low-molecular-weight heparins (LMWH) are effective, safe and convenient for anticoagulation. Their use is limited in patients with renal insufficiency (RI) because of bioaccumulation.
Evaluate pharmacokinetic data of dalteparin at a therapeutic dose in patients with RI.
Prospective observational cohort study. Inpatients were included into three groups according to glomerular filtration rate (GFR): A > or = 60, B 30-59, C < 30 mL min(-1) 1.73 m(-2). Dalteparin was injected subcutaneously (s.c.) twice daily. Peak plasma anti-factor Xa activity (anti-Xa) was measured and adjusted to applied dose and body weight after the first dose, on day 2, and every 2nd day afterwards. Bioaccumulation factor R was calculated as quotient of the last and the first adjusted anti-Xa. Data are shown as median (interquartile range, IQR).
Thirty-two patients (23 men) receiving dalteparin for > or = 2 days were analyzed. Follow-up was 6 days (IQR 4-10, range 2-22). Median dose was 90 (73-106) units kg(-1) per 12 h (P = 0.68). After the first dose, adjusted anti-Xa levels were 3.5 (2.6-5.0), 4.8 (3.3-5.5), 4.5 (3.7-7.5) x 10(-3) for the groups A, B, C; P = 0.26. On the last day, they were 6.1 (3.7-7.3), 7.1 (5.6-8.3), 10.2 (7.8-13.2) x 10(-3); A compared with C, P = 0.002. R was 1.46 (1.15-1.82), 1.36 (1.20-2.16) and 2.28 (1.53-2.93); A compared with C, P = 0.18.
Therapeutically dosed dalteparin accumulates in patients with severe RI (group C). Dose adjustments according to anti-Xa are recommended for dalteparin if used in this patient population. However, no simple dosing scheme can be suggested yet because of wide inter-individual variation.
低分子肝素（LMWH）在抗凝方面有效、安全且方便。由于生物蓄积，其在肾功能不全（RI）患者中的使用受到限制。
评估治疗剂量达肝素在 RI 患者中的药代动力学数据。
前瞻性观察队列研究。根据肾小球滤过率（GFR）将住院患者分为三组：A > 或 = 60、B 30-59、C < 30 mL min(-1) 1.73 m(-2)。达肝素皮下（s.c.）每日两次注射。在首次剂量后、第 2 天和之后每 2 天测量峰值血浆抗因子 Xa 活性（抗-Xa），并根据应用剂量和体重进行调整。生物蓄积因子 R 计算为最后一次和第一次调整的抗-Xa 的商。数据表示为中位数（四分位距，IQR）。
分析了 32 名（23 名男性）接受达肝素治疗> 或 = 2 天的患者。随访时间为 6 天（IQR 4-10，范围 2-22）。中位剂量为 90（73-106）单位 kg(-1) 每 12 小时（P = 0.68）。首次给药后，调整后的抗-Xa 水平分别为 A、B、C 组的 3.5（2.6-5.0）、4.8（3.3-5.5）、4.5（3.7-7.5）x 10(-3)；P = 0.26。最后一天，它们分别为 6.1（3.7-7.3）、7.1（5.6-8.3）、10.2（7.8-13.2）x 10(-3)；A 与 C 相比，P = 0.002。R 分别为 1.46（1.15-1.82）、1.36（1.20-2.16）和 2.28（1.53-2.93）；A 与 C 相比，P = 0.18。
在严重 RI（C 组）患者中，治疗剂量的达肝素会蓄积。如果在该患者人群中使用达肝素，建议根据抗-Xa 进行剂量调整。然而，由于个体间差异很大，目前还不能提出简单的剂量方案。
