Egfjord M, Rosenlund L, Hedegaard B, Buchardt H L, Stengel C, Gardar P, Andersen L, Andersen L
Medical Department P, Rigshospitalet, University of Copenhagen, Denmark.
Artif Organs. 1998 Aug;22(8):633-7. doi: 10.1046/j.1525-1594.1998.06008.x.
The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.
在40例从常规肝素（[CH]，丹麦巴勒鲁普利奥制药公司）转换为Innohep（IH）（Innohep [替扎肝素]，丹麦巴勒鲁普利奥制药公司）的患者以及13例已接受IH治疗的患者中，对Innohep（IH）的最小必要剂量（MNDI）进行了研究。通过肉眼检查，以4分制评估静脉腔和透析器中的凝血情况。在透析开始时，将IH作为大剂量注射剂注入透析器的动脉侧。IH的初始剂量为研究前使用的CH总剂量的50%（以各自的国际单位计）。根据静脉腔或透析器中的凝血情况，将IH剂量以500国际单位的逐步变化进行滴定，直至达到最低可能剂量，直到获得3次连续无凝血的透析疗程。转换前CH的总剂量（推注和输注）为6162±2100国际单位。在24例有动静脉内瘘的患者中，透析后插管部位的出血时间为7.1±2.8分钟（三次测量）。在达到MNDI之前，有8例患者被排除，3例是由于与肝素化无明显关联的出血（1例因牙龈出血，1例因鼻出血，1例因瘀斑），1例因脱发，2例因需要超过10000国际单位的IH，还有2例因焦虑导致治疗停止。转换后，MNDI相当于各自国际单位的66±26%。IH/CH转换率与血流速率和透析器类型显著相关。在转换为IH前后的3次连续疗程中进行比较时，拔管后的出血时间以及静脉腔中的凝血情况没有差异，而透析器凝血在视觉评分上从平均0.36降至0.19（p<0.01）。在研究期间未观察到完全凝血形成。MNDI与体重、血流速率和透析时间呈正相关（各自的相关系数r分别为0.58、0.44和0.30，p<0.05），并且也受透析器类型的影响。Hemoflow-FS中空纤维（德国巴德洪堡费森尤斯公司）、Lundia PRO平板（瑞典隆德甘布罗公司）和Polyflux中空纤维（甘布罗公司）的平均MNDI分别为2571、3727和5020国际单位（p<0.01，方差分析）。在慢性血液透析患者中，与CH类似，给予4250国际单位的IH推注可有效预防透析期间的体外凝血。然而，观察到MNDI存在相当大的个体差异，且与CH的需求无关，这就需要进行个体化剂量调整，以在最小出血风险的情况下获得最佳的凝血预防效果。
