Treib J, Haass A, Pindur G, Seyfert U T, Treib W, Grauer M T, Jung F, Wenzel E, Schimrigk K
Department of Neurology, University of the Saarland, Hamburg, Germany.
Thromb Haemost. 1995 Dec;74(6):1452-6.
The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch. 10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7. After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p < 0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs. 8.6 mg/ml). Hematocrit was lowered more (-30.5 vs. -23.5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p < 0.01), which exceeded the dilution effect. The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.
羟乙基淀粉（HES）的血浆清除率取决于初始分子量和取代度。到目前为止，羟乙基淀粉C2/C6取代率的临床相关性很少受到关注。10例脑血管循环障碍患者接受了为期10天的血液稀释治疗，使用的是10%的HES 200/0.5（平均分子量200 kD，取代度0.5），C2/C6比率为13.4。另一组10例患者接受了初始分子量和取代度相同但C2/C6比率为5.7的淀粉溶液。单次给药后，两组之间未观察到显著差异。重复给药后，在血液流变学、凝血和清除方面可检测到显著差异（p<0.01）。较大的C2/C6比率导致血管内平均分子量更高（95对84 kD），这反过来又导致治疗期间血清浓度升高幅度更大（14.7对8.6 mg/ml）。血细胞比容降低更多（-30.5%对-23.5%），血浆粘度升高更多。部分凝血活酶时间也有更明显的升高（+30%对+13%），因子VIII/血管性血友病因子复合物降低幅度大2倍（p<0.01），这超过了稀释效应。HES 200/0.5/13.4较高的C2/C6比率减缓了酶促降解。重复给予这种淀粉后，大分子积累，降解效率低下。在使用高取代度HES治疗后也观察到了相同的效果。这些大分子的积累导致有益的持久容量效应。缺点包括血浆粘度增加和凝血障碍，这不能仅用各自的稀释效应来解释。由于这些原因，C2/C6比率具有临床相关性，未来应纳入产品标签中。
