On March 25-26, 2015, the NHLBI sponsored a meeting on the State of the Science in Transfusion Medicine on the NIH campus in Bethesda. The goal of this meeting was to identify important research questions that could be answered in the next 5-10 years, and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and are focused on four topics: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Prior to the meeting, four committees, one for each topic, prepared five major questions for discussion along with a list of 5-10 additional questions for consideration. The meeting was attended by 330 registrants representing multiple stakeholders, including academic medicine, clinicians, industry, and government. The registrants had expertise in multiple relevant disciplines and included transfusion medicine physicians, surgeons, anesthesiologists, critical care physicians, cardiologists, hematologists, pediatricians, and basic scientists. The speakers, panelists, and participants identified unmet needs for improving clinical outcomes in transfusion medicine and proposed strategies to overcome existing obstacles and address unanswered questions.
Simone Glynn, MD, MSc, MPH
Chief, Blood Epidemiology and Clinical Therapeutics Branch Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute
Following an opening address by Dr. Keith Hoots of the NHLBI, which provided the context for the two-day meeting, the sessions for each of the four overarching topics (i.e., red blood cells, platelets, plasma, and donor issues) were organized identically and included a keynote address to all the attendees, a presentation of the committee’s proposed questions to all the attendees, a breakout group session to discuss the proposed questions, a restatement of the proposed questions with possible revisions to all the attendees, and a general discussion by all the attendees. Ample opportunity was provided to ask questions, state opinions, and propose alternatives. These open discussions were particularly valuable in ensuring that all voices were heard and all alternatives were thoughtfully considered. The large group sessions involving all of the attendees were valuable for ensuring that everyone had the opportunity to participate in everything; they also provided the opportunity to identify general cross-cutting concepts relevant to all four topics.
The meeting organizers, Drs. Simone Glynn, Darrell Triulzi, and Steven Spitalnik concluded the meeting by summarizing the overarching concepts and discussing next steps regarding the consensus questions identified by the speakers, committee members, and meeting participants.
Several cross-cutting themes relevant to each of the four topics were identified, including:
The list of the 5 most compelling questions necessitating additional basic, translational or clinical research are as follows, for each of the 4 major topics:
What determines which individuals will develop RBC alloimmune responses resulting in clinically meaningful sequelae?
Can we identify approaches to improve the potency and/or safety of transfusable RBCs?
What are optimal RBC transfusion thresholds for adult & pediatric cancer patients receiving chemotherapy that may improve functional status and quality of life?
Do liberal transfusion strategies result in lower rates of 30-day mortality as compared to restrictive transfusion strategies in patient populations not yet studied?
In critically ill patients, what is the best means to identify:
a. the degree to which anemia contributes to insufficient oxygen delivery
b. the likelihood that oxygen delivery will be improved by transfusion
What new methods of platelet preparation, processing, and storage must be developed to meet the hemostatic needs of patients in various clinical situations?
What are the indications, efficacy and safety of prophylactic platelet transfusions used to prevent bleeding before common invasive procedures?
What are the consequences, clinically and immunologically, of ABO or Rh type specific vs. non-type specific platelet transfusions?
How should platelet transfusions be used to treat active bleeding?
What knowledge and technological gaps exist regarding production, evaluation, and clinical translation of donor-independent platelets for transfusions?
At what prothrombin time (INR) threshold does prophylactic plasma transfusion prevent bleeding complications and improve outcomes in non-bleeding critically ill patients who will undergo an invasive procedure?
For critically ill patients with coagulopathy and associated World Health Organization grade 3 or 4 bleeding, which hemostatic therapy is preferred (e.g., plasma versus 4-factor prothrombin complex concentrates)?
Does the use of viscoelastic testing to guide plasma transfusion improve outcomes when compared to traditional coagulation testing?
Can a concentrated plasma product be developed, and would it be beneficial, for transfusion therapy?
For surgical patients with major bleeding due to an associated coagulation disorder, which hemostatic resuscitation strategy (i.e., goal-directed versus ratio-based) is superior?
How can blood centers prevent hypotensive reactions and reduce injuries after blood donation?
Are donor factors (e.g., age, gender), whole blood processing methods, and/or red cell storage solutions associated with in-hospital mortality and/or other measures of transfusion efficacy or harm in patients who have received red cell transfusions?
What is an acceptable risk-based framework for evaluating transfusion-related complications and transmissible diseases that would maintain or improve the sensitivity and specificity of the blood donor selection process? In addition, how can we change the process entirely or modify or eliminate questions to improve capture of relevant risk behaviors, while eliminating unnecessary deferral and retrieval policies that do not contribute to blood safety?
What are the biochemical and physiological responses to the acute blood and iron loss that occur during blood donation?
What is the effect of donation-induced iron deficiency on blood donor health?