International Blood Research & Reviews

The production and quality of Fresh Frozen Plasma (FFP) are governed by harmonised standards set by the European Directorate for the Quality of Medicines and HealthCare (EDQM). These standards emphasise maintaining protein activity and controlling residual leucocyte content to ensure product quality and patient safety. Although FFP was previously assumed to be acellular, recent studies have shown that residual leucocytes remain present. These cells can contribute to immunological reactions, transfusion-associated infections, and alloimmunisation in recipients. The holding time between whole blood collection and plasma processing is a pivotal factor. It determines the balance between leucocyte degradation and the preservation of labile plasma proteins, particularly coagulation factors such as FVIII, FV, Protein C, and Protein S. Short holding times may not sufficiently reduce leucocyte counts, thereby increasing the risk of immunological complications. In contrast, extended holding times can accelerate the decline of coagulation factors and reduce therapeutic efficacy. Additional variables such as temperature management, enzymatic activity from residual cells, and pH fluctuations also influence protein stability. These factors highlight the complex biochemical and cellular interactions that shape plasma quality. This review underscores the need for standardised, evidence-based holding times. Such standards should optimise both leucocyte inactivation and protein preservation while also accounting for operational constraints in blood establishments.

Future research should aim to quantify residual leucocyte activity, characterise subtle protein degradation, and link these findings with clinical outcomes. This will help refine FFP processing protocols and improve transfusion safety and effectiveness.