Cutting Edge Transfusion Strategies in the Civilian Setting

Educational Objectives

The goal of this program is to increase the use of new transfusion strategies. After hearing and assimilating this program, the clinician will be better able to:

1. Select individual transfusion components for trauma patients with massive hemorrhage.

2. Describe the benefits of whole blood transfusion.

Summary

Coagulopathy: affects all parts of clotting; inflammatory response generated from trauma and resuscitation efforts causes hyperfibrinolysis and fibrinogen dysfunction

Transfusion strategies: components can treat every problem associated with coagulopathy, including uncontrolled hemorrhage (plasma depresses inflammatory processes and prevents endotheliopathy; platelets treat platelet dysfunction); for massive bleeding, administer red blood cells (RBCs) and plasma in large quantities, platelets (1 apheresis unit equals 6 pooled units), and 1 bag of lactated Ringer’s solution (RBCs should be given with crystalloid)

Whole blood (WB): used in some institutions in United States; warm fresh WB — not available in United States because of risk for infection; transfused immediately or ≤8 hr after donation; stored at 22°C (room temperature) for ≤8 hr or 4°C for 24 hr; cold WB — available in United States and provided by American Red Cross; stored between 1°C and 6°C; fresh if transfused ≤48 hr; can be stored ≤35 days

Rationale for use: transfusion with individual components — 1 unit of RBCs, 1 apheresis unit of platelets, 1 unit of fresh frozen plasma (FFP), and 10-pack of cryoprecipitate produces hematocrit of 29%, platelet count of 87,000, coagulation activity of 65%, and 750 mg of fibrinogen; transfusion with WB — 1 bag can achieve normal hematocrit, normal platelet count, coagulation activity of 100%, and 1500 mg of fibrinogen; administration and maintaining ratio of individual products unnecessary (with WB, ratio self-contained); outcomes — patients who receive WB 10 times more likely to survive; effect from WB greater than Injury Severity Score or Glasgow Coma Scale score

Problems: determining universal donor — WB contains both RBCs (universal donor type O) and plasma (universal donor type AB); Nessen et al (2013) show that type O low antibody titer WB safe to use as universal donor (no difference in mortality and no transfusion reactions in patients who receive type-specific blood vs type O uncrossmatched blood); WB donors only male — plasma from female donors not used in United States; Seheult et al (2017) — in male trauma patients (27 recipients nontype O; 17 recipients type O) who received median of 1 unit WB, nontype O patients received 3 times more units; no adverse events related to transfusion; no differences in haptoglobin, free hemoglobin, or creatinine between patients receiving type-specific and nontype-specific WB; confirms type O WB safe to use as universal donor

Cold platelets: life span of platelets at room temperature limited by infectious complications (used ≤5 days); studies show that warm platelets remain in circulation longer than cold platelets (3.9 vs 1.3 days); however, trauma patients only need platelets to function for 30 min to stop bleeding; refrigeration permits longer storage (≤35 days in WB); aggregation testing shows that nonagitated cold platelets more functional than warm platelets; use of cold (4°C) platelets approved by Food and Drug Administration (FDA) and logistically and functionally superior

Plasma: FFP — obtained from WB; frozen at -20°C within 8 hr; stored ≤1 yr; freezing and thawing reduces function; requires 30 min to thaw (not logistically feasible for massive transfusion); thawed FFP can be stored ≤5 days with minimal reduction in function of factors V and VIII and protein S; plasma frozen within 24 hr after phlebotomy (FP24) — stored for 8 to 24 hr before freezing; cannot create thawed plasma from FP24; liquid plasma — never frozen; stored ≤26 days; largest waste of plasma comes from unused thawed plasma; freeze-dried plasma — not yet FDA-approved in United States; used in Germany (product from single donor [requires blood type compatibility] and stored ≤15 mo) and France (product from ≤11 donors [universal agent, not type-specific], pathogen-reduced, and stored ≤24 hr); in open label randomized trial of 48 trauma patients requiring emergent transfusion (Garrigue et al, 2018), patients who received FDP underwent transfusion earlier (elevates levels of fibrinogen) and needed less crystalloid and colloid (however, study small and not statistically significant); benefits — contains >1000 proteins; depresses functional inflammation; decreases endothelial permeability; rebuilds glycocalyx

Donor characteristics: Chassé et al (2016) report that sex and age of donor play major role in outcome for recipient (survival more likely if RBCs from older donor and less likely if RBCs from female donor); rodent studies using parabiosis show that proteins in plasma from younger animal can rejuvenate brain and muscles of older animal

Readings

Chassé M et al: Association of blood donor age and sex with recipient survival after red blood cell transfusion. JAMA Intern Med, 2016 Sep;176(9):1307-14; Garrigue D et al: French lyophilized plasma versus fresh frozen plasma for the initial management of trauma?induced coagulopathy: A randomized open?label trial. J Thromb Haemost, 2018 Mar;16(3):481-9; Nessen SC et al: Fresh whole blood use by forward surgical teams in Afghanistan is associated with improved survival compared to component therapy without platelets. Transfusion, 2013 Jan;53 Suppl 1:107S-113S; Pusateri AE et al: Dried plasma: State of the science and recent developments. Transfusion, 2016 Apr;56 Suppl 2:S128-39; Seheult JN et al: Measurement of haemolysis markers following transfusion of uncrossmatched, low-titre, group O+ whole blood in civilian trauma patients: Initial experience at a level 1 trauma centre. Transfus Med, 2017 Feb;27(1):30-5; Strandenes G et al: Low titer group O whole blood in emergency situations. Shock, 2014 May;41 Suppl 1:70-5.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. In his lecture, Dr. Schreiber presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Schreiber was recorded at Trauma, Critical Care & Acute Care Surgery 2018, held April 9-11, 2018, in Las Vegas, NV, and presented by the Trauma & Critical Care Foundation. For more information about upcoming CME activities presented by the Trauma & Critical Care Foundation, please visit trauma-criticalcare.com. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

EM361301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.