To minimize the risk of TRALI, a male-only kinase inhibitor ARQ197 plasma policy has been adopted in many countries – with marked reductions in TRALI [35]. Another potential mechanism involves interactions of biologically active mediators in stored plasma and lung endothelial cells. Other important transfusion-related complications include acute haemolytic reaction from anti-A and anti-B antibodies, and anaphylaxis [22].Massive bleedingMassive bleeding is defined as the loss of one blood volume within 24 hours, or as 50% blood loss within 3 hours or a bleeding rate of 150 ml/minute [38]. The physiological derangements and complications are proportional to the blood loss and to the time to correct shock. Loss of one blood volume and replacement with RBC only results in clotting factor levels dropping to approximately 30%, the minimal level thought to be required for adequate haemostasis [3,39].

Lower levels significantly prolong the prothrombin time and the activated partial thromboplastin time above 1.5�� normal [1]. FFP transfusion to replace clotting factors is often recommended for these patients but no studies exist supporting this practice [4]. Replacing one blood volume or more without FFP results in dilutional coagulopathy, diffuse microvascular bleeding and increased mortality [40,41].Current guidelines for FFP in massive bleedingThe principles of managing massive haemorrhage include rapid control of bleeding; replenishing the intravascular volume with crystalloid followed by RBC and, once coagulopathy is present or suspected, then adding FFP, platelets and cryoprecipitate; along with correction of acidosis and hypothermia.

Most current guidelines [1,39,42-44], including the European and US guidelines, recommend transfusing FFP, platelets and cryoprecipitate only when laboratory assays detect a deficit. The goal is to correct the assays as follows: FFP to correct the prothrombin time/activated partial thrombo plastin time to <1.5�� normal, platelets to raise the count to ��50 �� 109/l and cryoprecipitate to raise fibrinogen to ��1.0 g/l [1,42-44]. Where a laboratory is not available, these products are recommended after large infusions of crystalloid and RBC. The usual FFP dose in massive bleeding is 15 to 20 ml/kg or 3 to 6 units, which aims to raise clotting factors levels above 30% [3,38,39].Current crystalloid-based resuscitation guidelines initiate FFP transfusion late, often after more than one blood volume is lost and the patients have clinically overt coagulopathy [40,41]. Most recommendations are based on observations and expert opinion, often lacking high-level evidence. Many recommendations originated in studies conducted in nontrauma settings Carfilzomib and when RBC units had 150 to 300 ml plasma [1].