1. Massive Transfusion Mary Jo Drew, MD, MHSA Chief Medical Officer Pacific Northwest Blood Services Region

2. Massive Transfusion Definitions Transfusion replacement of patient’s blood volume at a rate exceeding the body’s ability to maintain blood elements at safe levels Replacement of 1-2 times the patient’s total blood volume in 24 hours or less

3. Massive transfusion in trauma Clinical priorities Airway/oxygenation Maintenance of intravascular volume via crystalloid and/or colloid infusion Maintenance of oxygen-carrying capacity via RBC transfusion Maintenance of coagulation integrity via transfusion of platelets, FP, and/or cryo

4. Pre-existing clinical problems Liver disease Coagulation abnormalities Shock Decreased tissue perfusion Acidosis Activation of coagulation system Hypothermia Diminished O 2 release Increased blood viscosity Coagulation abnormalities

5. Hazards of Massive Transfusion Hyperkalemia Increased potassium in stored RBCs Citrate toxicity Hypocalcemia, cardiac arrhythmias Coagulation abnormalities Due to dilution, hypothermia, DIC Down-regulation of immune system- controversial Post-transfusion viral infection

6. Dilutional effect of massive transfusion

7. Top reasons for massive transfusion GI bleeding Trauma Cardiovascular surgery LVAD insertions/removals Obstetric complications Liver transplant

8. RBC support in massive transfusion Goal To maintain O 2 -carrying capacity by keeping Hct > 25% At Hct < 20%, both O 2 delivery & platelet function are adversely affected Markedly decreased Hct affects blood cell flow rheology Platelets move toward center of vessel; further from endothelium where they are needed Increasing Hct improves platelet function

9. Immediate RBC support Emergency RBCs: “trauma units” Group O, uncrossmatched O+ for males, & females > 50 O- for childbearing age females; children < 18 Used until specimen for ABO/Rh typing can be obtained Type-specific RBCs Uncrossmatched, ABO/Rh identical units Crossmatch completed after product is issued Used when patient’s ABO/Rh type known

10. Changing blood groups When is it necessary to change blood groups in massive transfusion? Age & gender of patient Availability of type-specific RBCs Projection of anticipated use In young, Rh- females, switch ABO before Rh if possible If Rh- requirement will exceed supply, switch to Rh+ immediately

11. Changing blood groups Effects on crossmatch: Group A patient transfused with group O RBCs may become serologic group O Transfuse group O RBCs and group A plasma/platelets during acute phase to avoid confusion After acute event, when patient forward types as group A, switch back to group A RBCs May switch immediately if using RBCs stored in extended storage medium such as Adsol®--minimal plasma is present in these units

12. Coagulation problems Most common causes of coagulopathy are dilutional thrombocytopenia or DIC Platelet count < 50,000 after 10-15 units of RBCs Levels of important clotting factors nearly always remain > 15-25% FVIII is an acute phase reactant and concentrations increase in trauma PT/PTT elevations <1.5X normal rarely if ever cause bleeding

13. Coagulopathy in trauma resuscitation For some of the 93,000 patients each year in the US who die of traumatic injury, about 20,000 die of uncontrolled hemorrhage after reaching the hospital 3,000-4,000 of these deaths are potentially preventable Data from casualty care in Iraq suggest a higher ratio of transfused plasma to RBCs, 2:3 or even 1:1, has been associated with decreased rates of mortality Many studies have been retrospective & confounded by treatment biases imposed by degree of injury & resource availability in the field Questions remain as to which civilian trauma patients this protocol might benefit

14. Coagulopathy in trauma resuscitation Algorithms have been developed to recognize patients at risk for massive transfusion in both military & civilian settings Differences in type and degree of injury result in differing predictive criteria Two factors found to predict massive transfusion in civilian studies Mechanism of injury associated with hard to control hemorrhage Rapid bleeding Other data have emerged showing that 25% of seriously injured patients present with coagulopathy, most frequently a prolonged prothrombin time (PT)

15. Coagulopathy in trauma resuscitation Based on those data, the following findings on admission have been associated with shock and increased mortality: Prolonged PT or INR (>1.5) Low platelet count (<100K) Low hematocrit (<30%) Low fibrinogen (<100 mg/dL) High base deficit (>6) Low systolic BP (<80) Mechanisms of injury are complex, & not all civilian trauma patients with these findings or with certain types of trauma will be coagulopathic on admission

16. Coagulopathy in trauma resuscitation Coagulopathy can be associated with blunt or penetrating trauma Degree of tissue destruction is most important in determining degree of coagulopathy, not whether trauma is blunt or penetrating In US, penetrating trauma is frequently due to gunshot wounds, which is closer to the military experience

17. Treatment of coagulopathy of trauma Accumulated data to date suggest the use of a 2:3 or 1:1 ratio of plasma:RBCs may be useful in the treatment of acute coagulopathy of trauma Benefits of therapy must be balanced with the dangers of inappropriate use of plasma, primarily transfusion related acute lung injury (TRALI) Early use of platelets and cryoprecipitate should also be implemented to supply additional coagulation support Additional trials are underway to evaluate the true role of increased plasma ratios in these patients Experience suggests that the 2-3% of civilian trauma patients who arrive with early traumatic coagulopathy might benefit from such a protocol

18. Dilutional thrombocytopenia Defined as platelet count of <50,000 following transfusion of non-platelet containing blood components Can be seen after 10-15 units of RBCs when starting with normal platelet count Would be seen sooner if not for internal “transfusion” of platelets from spleen Not seen in all patients Check platelet count frequently & watch for diffuse bleeding or “oozing” in operative field

19. Other coagulation concerns Fibrinogen deficiency Most common cause of elevated PT/PTT in a massively transfused patient Levels <100 may cause spontaneous bleeding Monitor and give cryoprecipitate 2-3, 5 unit pools (10-15 units) usually sufficient initial dose, depending on patient size and degree of hypofibrinogenemia More rapid method of replenishing fibrinogen than plasma, as cryoprecipitate is a concentrate—10 units of cryo, at about 200 cc, has as much fibrinogen as 10 units of plasma, at about 2300 cc

20. Other coagulation concerns Disseminated intravascular coagulation (DIC) Once blamed on massive transfusion Usually a result of underlying disorder Massive tissue injury, head trauma, shock, sepsis, obstetrical bleeding can all result in DIC Occurs in 5-30% of patients with shock Pertinent lab studies include elevated D-dimer and fibrin split products (FSP), decreased FBG

21. Electrolyte imbalance Calcium Citrate anticoagulant chelates and decreases total & ionized serum calcium Twitches & tingling may lead to cardiac arrhythmia or coagulation abnormality Potassium Na/K pump efficiency less in stored RBCs; increased K in extracellular fluid Pumps regain capacity shortly after transfusion Hyperkalemia rarely a concern

22. Approach to massive transfusion Hematocrit Maintain >25% with RBCs Platelets Maintain >50,000 with platelets Coagulation Monitor PT/PTT for increase >1.5X ULN If bleeding, treat with FP Monitor FBG; if <100, give cryoprecipitate