Table 2.

Research priorities

Section	Research priorities
Transfusion ratios in massive bleeding	More high-quality, randomized data of massive transfusion protocols including high-ratio transfusion vs. low-ratio transfusion are required in trauma and non-trauma patients with massive bleeding More RCT data on impacts of massive transfusion protocols guided by empiric transfusion ratios vs. guided by point of care testing
Cold-stored platelets	RCTs involving conventional and cold-stored platelets are needed in patient populations where rapid control of hemorrhage is vital, such as trauma-associated or obstetric hemorrhage. Key outcomes include clinical and blood product use, effects on measured hemostatic parameters, and patient-important outcomes
Prothrombin complex concentrate in massive bleeding	RCT data demonstrating the effects of prothrombin complex concentrate (± fibrinogen concentrate) vs. conventional massive transfusion protocols are needed in both trauma and non-trauma populations with massive bleeding
Early fibrinogen replacement in massive bleeding	Large-scale trials, including clear fibrinogen testing strategies, targets, products (cryoprecipitate vs concentrate), and populations are needed to guide decisions on the role of fibrinogen early in resuscitation
Thromboelastography vs conventional coagulation testing in massive bleeding	Trials comparing the use of thromboelastography to conventional coagulation testing protocols are needed to demonstrate the effects and economic impacts of implementing thromboelastography across a variety of patient populations with massive bleeding; these should incorporate transfusion protocols (eg. ratios, alternative blood products)
Red blood cell transfusion	More research is needed on transfusions in patients undergoing vascular surgery, and other surgical populations at risk for significant bleeding and with cardiovascular comorbidities More research is needed on guiding transfusions in low-risk patients with bleeding, such as healthy postpartum women, and surgical patients with few comorbidities
Restrictive vs. liberal platelet transfusion in non-massive bleeding	More studies are needed to examine the difference in the transfusion practice of a restrictive versus a liberal platelet transfusion practice in terms of outcomes, effects, patient values and preferences, as well as resources required to implement such strategies
Restrictive vs liberal platelets in patients on antiplatelet medications	Further research is required to define the platelet transfusion strategy with the restrictive strategy being no platelet transfusion in other subgroups of patients with non-major bleeding patients This is an important research question as gastrointestinal bleeding is common and patients with cardiovascular diseases requiring antiplatelet therapy are increasing
Fibrinogen in non-massive bleeding	Research is needed on which which triggers should be used for “early” or “empiric” fibrinogen administration in patients with bleeding, and specific targets for replacement (fixed dose vs. use of viscoelastic testing)
Plasma in non-massive bleeding	Future research should focus on 1) targeted personalized trial of using any point of care testing to assess presence and type of coagulopathy and determine transfusion requirements compared to transfusing patients based on clinical presentation; 2) restrictive versus liberal plasma transfusion strategies in non-massively bleeding critically ill patients with a coagulopathy and 3) exploring the correction of coagulopathy versus non-correction of coagulopathy in non-massively bleeding critically ill patients
Point of care vs conventional in non-massive bleeding	RCTs comparing transfusion strategies guided by point of care testing vs. conventional coagulation testing, with and without fixed ratio blood product transfusions are needed to determine whether thomboelastography improves patient outcomes and impacts blood product use in critically ill patients
TXA in trauma and traumatic brain injury	More research is required to identify subgroups most likely to benefit from the use of TXA and the role of individualized patient use guided by thromboelastometry and conventional coagulation tests
TXA in subarachnoid hemorrhage	More research is needed on the role of TXA in specific patient populations, eg. those with delayed or challenging aneurysm securement
TXA in intracranial hemorrhage	Given residual uncertainty around the effects of TXA on patient-important outcomes of mortality and functional recovery, further research is required. Other trials are planned or ongoing (NCT03385928, NCT02625948, NCT03044184, NCT02866838,ChiCTR1900027065), and will assist in addressing this area of uncertainty
TXA in gastrointestinal bleeding	More evidence is required evaluating the role of enteral and low-dose intravenous TXA, and the potential role of TXA as rescue therapy in refractory hemorrhage
TXA in postpartum	More research is needed on identifying which patients with PPH are most likely to benefit from TXA. For instance, it may be more helpful in patients with PPH after vaginal rather than caesarean delivery [38].

RCT  randomized controlled trials; TXA tranexamic acid