The literature review identified 28 studies as being relevant. Of these, six were Level III studies^4,5,70-73 and the remainder were Level IV.^{54,61,62,64-66,74-89} Some studies^71,72 involved a military population and should therefore be interpreted with caution because of baseline differences between military and civilian populations (e.g. higher incidence of severe, penetrating trauma).

A survival advantage is associated with decreasing the ratio of RBCs to fresh frozen plasma (FFP), platelets or cryoprecipitate/fibrinogen administered to patients undergoing massive transfusion.^65,76,78,89 The decrease in mortality associated with administering low versus high ratios of RBCs to blood components was associated with a significant decrease in deaths from exsanguination. This decrease was attributed to administration of lower ratios of RBCs to FFP, platelets, apheresis platelets and fibrinogen.^61,65,76,79

More deaths were reported in patients receiving high ratios of RBCs to blood components compared with low-ratio recipients. However, these results should be interpreted carefully, because of the potential for survival bias (that is, patients who die early are more likely to have received a higher RBC:component ratio).⁸⁴

The types and content of the studies varied in terms of blood components and the ratios given; therefore, the optimum target ratio is difficult to determine. In trauma patients, a ratio of RBC:FFP:platelets of ≤ 2:1:1 was associated with improved survival.^5,70,71 A number of these studies used a ratio of, or near to, 1:1.^{4,5,70,71,76,78,79,85,89} Other studies used a ratio of < 2:1:1.^5,70,71 However, based on analysis of the available studies and the possibility of survival bias, it is not possible to recommend a target ratio of RBC:FFP:platelets.

In non-trauma patients, there were insufficient data to support or refute the use of a defined ratio of blood component replacement. Although these patients do not have the initial coagulopathy commonly seen in trauma, critical bleeding may still result in development of hypothermia, acidosis and coagulopathy. Coordination of the management of these patients through use of an MTP is recommended. Blood component replacement should be guided by clinical assessment and results of coagulation tests.

Fibrinogen is an essential component of the coagulation system, due to its role in initial platelet aggregation and formation of a stable fibrin clot. Current critical bleeding guidelines recommend keeping the fibrinogen level above 1.0 g/L.^14,90 If fibrinogen levels are not maintained using FFP, replacement using cryoprecipitate or fibrinogen concentrate is indicated. However, in the setting of major obstetric haemorrhage, early administration of cryoprecipitate or fibrinogen concentrate may be necessary.

Optimum management requires prompt action, as well as good communication and coordination between treating clinicians, diagnostic laboratories and the transfusion service provider. This is best facilitated by the development and deployment of an MTP that clearly outlines responsibilities and requirements. A template MTP was developed by the CRG (see Section 4.10). Local adaptation of such a protocol – taking into account blood component availability and other resources – fosters a coordinated multidisciplinary approach.

Evidence statement

In trauma patients with critical bleeding requiring massive transfusion, the use of a protocol that includes the dose, timing and ratio of blood component therapy is associated with reduced mortality.4,5 (See evidence matrix 2 in Appendix E.) In trauma patients with critical bleeding requiring massive transfusion, a ratio of ≤ 2:1:1 of RBCs:FFP:platelets is associated with reduced mortality.5,70,71 However, due to the possibility of survivor bias, it is not possible to recommend a target ratio of RBC:FFP:platelets. (See evidence matrix 3 in Appendix E.) In trauma patients with critical bleeding requiring massive transfusion, early transfusion of FFP and platelets is associated with reduced mortality and subsequent RBC requirements.85,89 (See evidence matrix 4 in Appendix E.) FFP, fresh frozen plasma; RBC, red blood cell = A = B = C = D (See table 2.2)

Practice points