Table 2

Challenges and proposed solutions to future clinical trials on haemostatic resuscitation

Most important challenges

Proposed solutions

Avoid survivorship bias

Exclude patients not expected to live long enough to receive plasma

Precise documentation of the time of transfusions and death

Perform analysis of transfusion as a time-dependent variable

Avoid contamination of the control arm and avoid delay in initiating 1:1 transfusions in the intervention arm

Transfusion guidelines for both arms clear and easy to follow

Close cooperation between blood bank, trauma, anaesthesia and critical care

Thawed AB plasma 24/7 or rapid thawing (microwave)

Minimize time for results of laboratory tests - consider point-of-care testing

Multiple interventions concomitantly tested

Standardize all aspects of resuscitation (that is, amount and type of intravenous fluid; procoagulant drugs) in control and intervention groups

Measure clotting factor levels

Discriminate coagulopathic from mechanical bleeding

Measure indicators of coagulopathy:

• Thromboelastography

• Clotting factor assays

• Markers of hyperfibrinolysis

• Tissue hypoperfusion (lactate, base deficit)

• Progression of bleeding by computerized tomography scan (that is, progression brain

contusion, retroperitoneal haematomas)

• Ask the physician's opinion (that is, surgeon, anaesthetist, intensivist)

Immediate cessation of component therapy

Evidence that bleeding has stopped

Consider ending by 6 hours

Outcome

Consider restoration of haemostasis competence

Need for large samples

Consider a feasibility trial prior to a large multicentre trial to identify major challenges

Consent

Need for delayed consent

Nascimento et al. Critical Care 2010 14:202   doi:10.1186/cc8205