Studies on the Procurement of Blood Coagulation Factor VIII in vitro Studies on Blood Components Prepared in Half-Strength Citrate Anticoagulant

Abstract

The effect of replacing a standard citrate anticoagulant with one containing half the amount of citrate on the in vitro properties of components prepared from blood donations was investigated. This resulted in a significant improvement in factor VIII stability such that there was little loss during overnight storage, and this was reflected in the factor VIII yield in cryoprecipitate. The quality of cellular components in red cell units stored up to 35 days or platelet concentrates stored up to 7 days was not adversely affected. Although initial levels were similar to those in standard anticoagulant, the extent of fibrinopeptide A generation and complement C3 breakdown in red cell units stored for 35 days in half-strength citrate was somewhat increased.

Sodium citrate contributes to the platelet storage lesion

“…Interestingly, previous studies suggested that concentrations of citrate below 8 mM may cause activation of the coagulation cascade . In each of these prior studies, there are underlying variables that may have contributed to the observed clotting.…”

“…Prowse et al collected whole blood into CPD.A1 anticoagulant (approx. 20 mM) and further diluted with phosphate‐dextrose solution to achieve concentrations as low as 4 mM citrate . These samples, however, were stored as whole blood for 3 hours or 23 hours at room temperature.…”

“…Therefore, it is likely that PLT storage in the presence of RBC's may contribute to clotting through RBC ADP release and PLT activation rather than citrate concentration. Furthermore, the same group performed an additional study in isolated PLT concentrates with half‐strength anticoagulant . Under these conditions, no spontaneous aggregation or clotting was observed, while pH and cell quality was determined to be better than corresponding full‐strength anticoagulant donations .…”

“…Importantly, during the development of platelet additive solutions (PASs), citrate was introduced into the second generation of commercial PAS solution (PAS‐II) and has remained largely in all subsequent generations at a concentration of 10 mM (PAS‐III, PAS‐IIIM, PAS‐G, and M‐Sol) . It has been suggested that citrate should remain in these solutions because anything below 8 mM/L may trigger clotting …”

Platelet storage media

“…On the other hand, increased production of lactate associated with higher concentrations of citrate can be neutralized by addition of acetate . However, a citrate concentration of at least 8 m m seems to be a minimum level, as clotting problems due to activation of coagulation can be expected at lower concentrations .…”