Calcium carbonate polymorphs enhance coagulation in citrated blood via platelet concentration and calcium release.

Citrate, widely used as an anticoagulant in transfusion and extracorporeal therapies, disrupts calcium-dependent coagulation by chelating ionized calcium, resulting in hypocalcemia and severe coagulopathy. This interference elevates bleeding risks and may trigger hemorrhagic shock. Current treatments for local bleedings in the context of citrate-induced coagulopathy include topical hemostats that either provide a physical barrier to the bleeding or activate platelets and the coagulation cascade. This study investigates the potential of calcium carbonate (CaCO3) to counteract the citrate coagulopathic effect by promoting coagulation through calcium ion release and platelet aggregation. In vitro assays demonstrated that various CaCO3 polymorphs significantly enhance coagulation in citrated blood. Both coral-derived aragonite and synthetic calcite reduced coagulation time, with calcite particles achieving up to a 2-fold reduction. Prothrombin and Partial Thromboplastin Times decreased by 13% and 24%, respectively, with calcite treatment. Moreover, calcite reduced circulating platelet counts by 13% while directly binding platelets, indicating effective recruitment, and raised free calcium levels in plasma by 2.6-fold compared to controls. These dual effects-calcium elevation and platelet concentration-suggest that CaCO3 is a promising hemostatic agent for addressing bleeding in citrate-induced coagulopathy, offering innovative solutions for transfusion medicine and critical care.