Serial measurement of clotting factors in thawed plasma stored for 5 days

Abstract

The seventeenth edition of Standards for Blood Banks and Transfusion Services 1 changed the transfusion expiration time for FFP from no more than 24 hours after thawing to up to 5 days when thawed plasma is used to treat coagulopathies other than factor VIII (FVIII) deficiency. Despite this, thawed plasma is frequently discarded at less than 5 days of age, most likely because of the belief that coagulation factor activity decreases during extended storage to clinically unsuitable levels. We designed a study to analyze the activity level of factors I (fibrinogen), II, V, VII, VIII, and X and in thawed plasma stored at 1 to 6°C for 5 days.Five units each of types A, B, and O FFP designated for study were thawed at 37°C, divided into five equal volumes in plastic bags, and stored at 1 to 6°C for 5 days. Daily aliquots of plasma from the divided volumes were frozen at -70°C. For each aliquot, factors II, V, VII, VIII, and X and fibrinogen were assayed by using factor-deficient commercial plasma (Dade Behring, Marburg, Germany) and an automated coagulation analyzer (Sysmex CA 6000, TOA Medical Electronics Company, Kobe, Japan). We used ABOspecific units, because FVIII is affected by ABO blood group.As expected, FVIII, being heat labile, had the greatest decline in activity, with a drop of 28 percent from the original level of activity within the first 24 hours of storage 2 (Table 1). Comparison of FVIII activity at Day 1 with that at Day 3 was significant (p values for types A, B, and O were <0.004, <0.02, and 0.001, respectively). While freeze-thaw cycles may affect factor activity levels to some extent, in this study, the freeze-thaw cycles were identical for all aliquots; hence, any decrease in FVIII would be similar. Therefore, the decrease in FVIII at 4°C during the study period represents a true decline in activity level from that after the freeze-thaw cycles. Because FFP is indicated to treat coagulopathy but not isolated FVIII deficiency, most patients requiring FFP, including liver disease patients, have clinically adequate or even high plasma levels of FVIII, which is an acute-phase reactant. 3,4 Factor V is also heat labile (37°C), but it appears to be stable at 4°C. All other clotting factors are stable for over 5 days. 5 Thawed plasma stored up to 5 days can safely be used to treat the coagulopathy of liver disease, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulation and to reverse the effect of coumadin. Because all factors except fibrinogen decreased with extended storage, we elected at this time to use a more conservative expiration time of 3 days rather than 5 days. Extension to 3 days of the expiration time for thawed plasma in our institution reduced wastage from 5.1 percent with 24-hour storage at 4°C to 1.1 percent with 3-day storage, for a total estimated cost savings of $17,800 per year.

Study of coagulation factor activities in apheresed thawed fresh frozen plasma at 1–6°C for five days

“…Downes and co-workers studied activities of coagulation factors II, V, VII, X, and fibrinogen in thawed fresh frozen plasma kept at 1-6°C over a 5-day period. They reported no significant decrease in any of the factors studied except factor VIII, which dropped significantly on day 5 (35-41%) compared to day 1 [4]. Buchta and co-workers investigated the activities of coagulation factors II, V, VII, VIII, IX, X, XI, XII, and fibrinogen, antithrombin, protein C, protein S, and von Willebrand antigen in thawed solvent/detergent-treated fresh frozen plasma kept at 4°C for 6 days.…”

“…Various investigators studied the stability of the coagulation factors either at room temperature or at 1-6°C for 24 hours or thawing with subsequent freezing after storage for 24 hours at 1-6°C [1][2][3]. Three recent reports have studied the stability of coagulation factors over 5 to 10 days [4][5][6]. Plasma from whole blood has been approved for use up to 5 days after thawing as long as the system is closed [7].…”

A Massive Transfusion Protocol to Decrease Blood Component Use and Costs

“…The trauma team initiates the MTP with a phone call or a written order ( Table 1). If the blood type of the patient is not known, the first shipment consists of 5 units of blood group O Rh-negative PRBCs and 2 units of blood group AB thawed plasma (once thawed, fresh frozen plasma can be kept for up to 5 days at 4°C; however, it is then labeled as thawed plasma) 10 (Table 1); if the patient's blood group is known, the shipment consists of type-specific PRBCs and thawed plasma (Table 1). In shipments 3 and 6, rFVIIa is given.…”

Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution

“…In thawed FFP kept at 1-6°C, residual levels of labile FV remain adequate for 5 days. 108 Such plasma may be useful when FFP is acutely needed for massive transfusion. Several retrospective analyses demonstrated the potential clinical benefit of aggressive hemostatic resuscitation using the empirical transfusion ratio of FFP:RBC over 1:1 in military and civilian trauma cases.…”