Effect of in vitro hemodilution with hydroxyethyl starch and dextran on the activity of plasma clotting factors.

Objective: A recent thrombelastography study indicated a compromised in vitro blood coagulation after 10:10 (equal parts of blood and infusion) and 10:4 (10 parts blood to four parts infusion) hemodilution with several plasma substitutes. Oncovertin N (Oncovertin) (a 10% dextran 40 solution) had the strongest anticoagulant effect of all solutions tested, and HAES-sterile 10% (HAES) (a 10% hydroxyethyl starch 200/0.5 solution) showed the strongest effect of five different hydroxyethyl starch preparations. The aim of this study was to determine how in vitro hemodilution with HAES and Oncovertin affects the activity of coagulation factors.

Design: HAES and Oncovertin were tested to determine the intrinsic effect of colloid molecules, as opposed to hemodilution. Normal saline (NaCl) and nonlactated Ringer solution were used as noncolloidal controls.

Setting: University research institute.

Patients: Six healthy volunteers.

Interventions: Twenty milliliters of blood was obtained from each subject.

Measurements And Main Results: Prothrombin index, activated partial prothrombin time, soluble fibrin monomers, and the activity of coagulation factors I, II, V, VII, VIII, IX, X, XI, and XII were measured with the Behring Chromotimer according to the manufacturer's instructions. Two dilution ratios of citrated blood to infusion were used: 10:10 (equal parts of blood and infusion) and 10:4 (10 parts blood to four parts infusion). Baseline was undiluted. Hemodilution with NaCl at both 10:4 and 10:10 influenced the coagulation variables measured. The activities of factors I, VII, and soluble fibrin monomers were less influenced than expected by hemodilution alone. The activities of factors II, V, IX, and XI were significantly (p <.04) lower with both 10:4 and 10:10 dilution with NaCl. In the assays for factors IX, XI, and XII, clots formed immediately after adding the appropriate reagents in the presence of Ringer solution at 10:10 hemodilution, so that the activities of those factors could not be measured. For the other factors and for 10:4 dilution, the outcome after Ringer solution was similar to that of NaCl. The activities were less influenced after 10:4 hemodilution with both HAES and Oncovertin than after dilution with NaCl and Ringer solution, with no significant differences from baseline. At 10:10 hemodilution with both HAES and Oncovertin, several factor activities were significantly (p <.04) lower than baseline.

Conclusions: Both NaCl and Ringer solution cause measurable effects on coagulation factors at 10:4 hemodilution that can be explained by hemodilution alone. The effects on clotting factors of 10:4 hemodilution with HAES and Oncovertin were not significant. Even at 10:10 hemodilution with HAES or Oncovertin, the reduction in factor activities, although significantly (p <.04) different from baseline, was less than what was expected by dilution alone.