Effects of hydroxyethyl starch on blood coagulation, particularly factor VIII

Abstract

The effects of hydroxyethyl starch (HES) on hemostasis were investigated extensively. In order to simulate acute blood loss due to surgery or trauma, one unit (450 ml) of blood was drawn from normal healthy men. This was followed by a 1-liter infusion over 60 minutes of either 6 percent HES, 5 percent albumin, or 0.9 percent sodium chloride (NaCl) as replacement. Coagulation studies were performed before phlebotomy, before infusion and at 0, 4, 20, 27, and 92 hours following infusion. Following infusion of HES and albumin, plasma fibrinogen and antithrombin-III levels fell slightly due to plasma volume expansion and hemodilution. In subjects receiving HES, partial thromboplastin times (PTTs) were significantly (p less than .05) prolonged and factor VIII activities were significantly (p less than .05) decreased when compared to the albumin and NaCl groups. These findings could not be attributed solely to hemodilution. The effects of HES on PTT and factor VIII could not be correlated with plasma HES levels; neither could they be reproduced in vitro by mixing HES with normal plasma. Mean values of the following studies remained normal after infusion of all replacement fluids: prothrombin time, bleeding time, fibrin monomer, fibrin-fibrinogen degradation products, platelet adhesion, circulating platelet aggregates, and platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)

Coagulation effects of in vitro serial haemodilution with a balanced electrolyte hetastarch solution compared with a saline‐based hetastarch solution and lactated Ringer's solution*

“…The progressive decrease in maximum amplitude of the starches over the dilution range (Fig. 4) can be explained by the documented dose-related inhibition of von Willebrand's factor (antigen and coagulant) by HS ⁄ sal solutions [11]. Since the maximum amplitude is largely dependent on platelet function, the different behaviour of maximum amplitude with dilution in comparison to the other thrombelastographÒ variables is entirely predictable.…”

A novel hydroxyethyl starch (Voluven®) for effective perioperative plasma volume substitution in cardiac surgery

“…4,5 With large volumes of HES infused perioperatively, inhibitory effects on hemostasis, most notably on the von-Willebrand factor, have been reported. [6][7][8] Impairment of hemostasis by HES is most pronounced with large and highly substituted HES molecules, such as hetastarch, which has an average molecular weight of 450,000 dalton and a degree of substitution of 0.7 (HES 450/0.7), or after long-term use of medium molecular weight starches with a high degree of substitution (200,000 dalton; 0.62-0.66). 9,10 These HES types are characterised by delayed degradation in vivoand accumulation of HES molecules in plasma and tissue.…”

A Comparative Coagulopathic Study for Treatment of Vasospasm by Using Low- and High-molecular Weight Hydroxyethyl Starches

“…Although the etiology Coagulopathy with the Use of Hydroxyethyl Starch｜SH Hwang, et al of this improvement was unclear, they suggested theories including hemodilution, decreased plasma viscosity, increased cardiac output, or mild elevation of clotting time 7,12,20) . The mild elevation of clotting time was ascribed to precipitation by hetastarch of factor VIII 5,7,10,15) . Studies in humans used doses lower than those necessary for the treatment of vasospasm in normal volunteers 8,15) .…”

“…The mild elevation of clotting time was ascribed to precipitation by hetastarch of factor VIII 5,7,10,15) . Studies in humans used doses lower than those necessary for the treatment of vasospasm in normal volunteers 8,15) . We thought that 500 cc/day of hetastarch was inadequate to maintain pulmonary capillary wedge pressure and hemodilution.…”