5.1.2 Effect of dose, timing and ratio of component therapy on outcomes
Question 2 (interventional)
In patients with critical bleeding requiring massive transfusion, does the dose, timing and ratio (algorithm) of RBCs to blood component therapy (FFP, platelets, cryoprecipitate or fibrinogen concentrate) influence morbidity, mortality and transfusion rate?
FFP, fresh frozen plasma; RBC, red blood cell
In the complex setting of critical bleeding requiring massive transfusion, there are many constraints to the design of clinical trials of blood replacement strategies. A major historical problem has been the inability to control for the transfusion decision, which includes not only the defined threshold for red cell administration, but also the indication for component therapy (i.e. FFP, platelets and cryoprecipitate).
The best evidence examining the use of specific ratios of RBC : FFP : platelets came from studies of trauma patients with critical bleeding requiring massive transfusion in the military setting: however, there are few studies in other clinical settings. Also, the studies did not account for the possibility of survivor bias (e.g. patients who die early may receive less FFP than those who survive, so mortality may be lower in patients transfused with more FFP). Thus, it was not possible to recommend a specific ratio.
The strength of evidence related to this intervention would be increased if the design of clinical trials were to include the need to prospectively control for the use of predetermined defined ratios (algorithm based) compared to goal-directed component therapy. The effect of each intervention would also need to be assessed by its effect on the changes in the relevant coagulation measurement (platelet count for platelets, INR or PT for FFP, and fibrinogen for cryoprecipitate or fibrinogen concentrate) as well as the effect on morbidity, mortality and transfusion rate.
Current published critical bleeding guidelines recommend keeping the fibrinogen level above 1.0 g/L. 14,90 In the setting of major obstetric haemorrhage, early administration of cryoprecipitate or fibrinogen concentrate may be necessary.
Further research is needed to:
- compare goal-directed therapy to the use of specific ratios of RBCs to blood components in all patients with critical bleeding requiring massive transfusion (including time of administration of component therapy)
- determine the optimum level of fibrinogen and the role of fibrinogen concentrate in critically bleeding patients requiring massive transfusion
- evaluate the role of MTPs.