Effect of Hemodilution In Vitro with Hydroxyethyl Starch on Hemostasis

BACKGROUND Hydroxyethyl starch (HES) solutions are used for volume expansion during surgery. We aimed to investigate how 6%HES 130/0.4 affects hemostasis. MATERIAL AND METHODS Blood samples were collected from 12 healthy adult volunteers, diluting with 6%HES 130/0.4 (HES group) or Ringer lactate solution (RL control group). The hemodilution ratio (HR) of citrated blood volume to plasma substitute volume was 10: 0 (undiluted), 10: 2, 10: 4, and 10: 6. Clotting factors activity was measured. Thrombin generation was monitored. Platelet function was analyzed. RESULTS 1) Activity of coagulation factor was decreased with increasing HR compared to undiluted baseline, and the activity of FVIII was significantly decreased in HES vs. RL. 2) Calibrated automated thrombography (CAT) results showed HES extended lag time, time to peak (ttpeak), start tail, and decreased peak of thrombin generation. Although lag time and ttpeak were significantly prolonged in HES vs. RL, endogenous thrombin potential (ETP) did not change. 3) Flow cytometric (FCM) analysis showed that HES reduced platelet phospholipids serine (PS) vs. baseline and RL. 4) HES significantly decreased antithrombin activity (AT: A) of the anticoagulant system with increasing HR vs. baseline and RL. 5) For fibrinolytic system, HES did not affect fibrinogen degradation products (FDP) and D-dimers (D-D) vs. baseline, or α2-antiplasmin (α2-AP) vs. RL. CONCLUSIONS By reducing FVIII activity and platelet PS expression, HES interfered with PS combining to FXIa, FVIIIa, and FVa, which affected the acceleration and explosion stage of thrombin. The decreased velocity and peak of thrombin generation delays and reduces clot formation. Combined 6%HES 130/0.4 decreased anticoagulant activity and may have clinical utility.