Gelatin 4% and hydroxyethyl starch (130/0.42) impair clot formation in a human ex vivo whole-blood resuscitation model

Abstract Background Colloid solutions provide effective intravascular volume expansion but can impair hemostasis, which is particularly critical after trauma-associated hemorrhagic shock. The differential effects of specific colloids on plasmatic coagulation, platelet function and complement activation, especially when used alongside crystalloids, are still underexplored. We therefore examined graded hemodilution with gelatin or hydroxyethyl starch, alone and in combination with a balanced crystalloid, in an ex vivo human whole-blood model over time. Methods We used a citrate- and heparin-free human ex vivo whole-blood model to assess the effects of volume dilution with a balanced crystalloid (Jonosteril), gelatin solution (Gelafundin 4%) and hydroxyethyl starch (HES 130/0.42, 6%; Tetraspan). Whole-blood was diluted at increasing ratios up to 4:6 (diluent:blood), incubated for 30 minutes at 37 °C and analyzed for blood gases, standard coagulation tests, platelet activation (CD62P), von Willebrand factor (vWF), thrombin–antithrombin complexes, complement activation and viscoelastic parameters by ROTEM (EXTEM, INTEM, FIBTEM). Results At high dilution ratios, colloid-diluted samples exhibited more frequent macroscopic clotting and significantly lower pH with more pronounced base deficit than Jonosteril. Gelafundin, but not Jonosteril or Tetraspan, increased vWF levels over time, while CD62P expression, thrombin-antithrombin complexes and complement markers remained unchanged. ROTEM revealed a clearly hypocoagulable profile after dilution with Gelafundin or Tetraspan, most pronounced with HES, with prolonged clotting time and clot formation time, reduced a-angle and maximum clot firmness. When combining Jonosteril with increasing colloid fractions at fixed dilution, these changes followed a non-linear, ratio-dependent pattern. Conclusion Balanced colloids, particularly HES 130/0.42, exert intrinsic, ratio-dependent adverse effects on clot formation beyond simple dilution, suggesting that hemostatic safety may depend not only on fluid type but also on the tolerated proportion of colloid within resuscitation strategies.