Coagulation, hemostasis, and plasma expanders:a quarter century enigma

Area of Science:

• Hematology
• Biochemistry
• Pharmacology

Background:

• Hemostatic failure is a known complication of macromolecular plasma substitutes.
• The exact mechanisms underlying this complication remain unclear despite extensive research.

Purpose of the Study:

• To elucidate the mechanisms of hemostatic failure induced by macromolecular plasma substitutes.
• To investigate the interaction of colloids with specific clotting factors and their clinical implications.

Main Methods:

• Analysis of plasma precipitates formed by dextran and hydroxyethyl starch.
• Investigation of the effects of these precipitates on clotting factors (Factor I, Factor VIII, von Willebrand factor).
• Assessment of platelet function and microcirculatory changes post-infusion.

Main Results:

• Colloid macromolecules precipitate Factors I, VIII, and fibrin monomer from plasma, forming a cryo-Factor I-like substance.
• This precipitation is dependent on colloid size, concentration, and viscosity.
• Dextran and hydroxyethyl starch accelerate thrombin clotting of plasma and purified Factor I, while albumin and hemoglobin do not.
• Dextran infusion leads to poor platelet function and capillary abnormalities resembling von Willebrand disease.

Conclusions:

• The hemostatic defect is likely an induced von Willebrand disease or disseminated intravascular clotting.
• Mechanisms include precipitation/removal of clotting factors, microcirculatory abnormalities, and platelet malfunction.
• Reported antithrombotic activity may stem from these same actions.