Massive Transfusion And Coagulopathy

1. Massive Transfusion And Coagulopathy Christine Mai, MD Faculty Advisor: Mauricio Gonzalez, MD Department of Anesthesiology Boston University Medical Center

2. Guidelines to Blood Product Transfusions • In 1994, the ASA established the Task Force on Blood Component Therapy to develop evidence-based guidelines for transfusing blood products in perioperative and peripartum settings • 22 million blood components transfused yearly • Benefits: improved tissue oxygenation and decreased bleeding • Risks: Transmission of infectious diseases, hemolytic and nonhemolytic transfusion reactions, immunosuppression, alloimmunization, coagulopathy

3. Massive Transfusion American Association of Blood Banks definition: replacement of one blood volume (equivalent to 10 units of blood) in any 24 hr period, or half of the blood volume (5 units of blood) in any four-hour period

4. American College of Surgeon’s Classes of Acute Hemorrhage

5. Parameters For Fluid Replacement • Maintenance • Deficits • Insensible loss • Estimated blood loss

6. Maintenance • 4:2:1 Rule or Calculate Wt +40 cc • Calculated weight: (IBW + ABW)/2 • IBW male: 110 lbs + 7 lbs * in > 5’ female: 100 lbs + 6 lbs * in > 5’ Deficits • NPO status Calculated Wt x hrs NPO x 0.7 • Bowel prep ~ 1200cc • Diuretics/ Urine output • NGT drainage • CT drainage

7. Insensible Loss Case TypeVolume Non-open 2-3 cc/kg/hr Open 4-6 cc/kg/hr Major Abdominal 6-10 cc/kg/hr Trauma > 10 cc/kg/hr (Volume based on Calculated Weight)

8. Estimated Blood Loss • The 3: 1 Rule, replace 3 cc crystalloid : 1 cc blood loss • The 1:1 Rule, replace 1 cc colloid : 1 cc blood loss Allowable Blood Loss (Hct present - Hct allowable) + EBV Hct present Estimated Blood Volume Adults: 75 cc/kg Infants: 80 cc/kg Neonates: 85cc/kg

9. Fluid Resuscitation Crystalloids

10. Type and Screen • Screen for ABO-Rh type and most common antibodies • ABO incompatibility is a tragic and severe reaction, resulting in rapid intravenous hemolysis • Ordered during elective cases when the probability of blood loss and transfusion are high • If blood is needed for emergent transfusion, a crossmatch can be performed to reconfirm ABO-Rh typing • Reactions against lower-incident antigens may still occur • Emergency trauma cases: Type O Rh-Negative (Universal Donor) Uncrossmatched Blood transfused until a Type and Cross clot is tested

11. Type and Crossmatching • Crossmatching -Trial transfusion within a test tube between donor RBCs and recipient serum to detect a potential for serious transfusion reaction - 3 Phases: -Reconfirm ABO-Rh typing - Detect antibodies that are incomplete or do not agglutinate easily - Detect antibodies in other blood group systems (ie. Rh, Kell, Kidd, Duffy) • Antibody screening • Trial transfusion between the recipient’s serum and commercially supplied RBCs with antigens that will react with antibodies commonly implicated in non-ABO hemolytic transfusion reactions • Donor’s serum also screened for unexpected antibodies to prevent their introduction to the recipient’s serum • Otherwise known as the Coomb’s test.

12. Blood Products Transfusion • Packed Red Blood Cells • Fresh Frozen Plasma • Platelets • Cryoprecipitate

13. Packed Red Blood Cells • Approx. 12 000 000 units of RBC are transfused yearly in the US • Indicated for patients needing red cells for oxygen carrying capacity rather than for volume replacement (ie. CHF patients) • 70% Hct in pRBC compared to 40% Hct in whole blood • Each unit contains 250-350 cc of red cells, increases Hct 3-4% or increases Hgb 1g/dL • Large amount of transfusions should be warmed to 370C • Dilute pRBCs with either normal saline or plasmalyte when giving massive transfusions • Avoid Lactated Ringers because calcium can chealate with citrate

14. Citrate Toxicity • Calcium binding to citrate preservative in transfused blood → Hypocalcemia • Signs of citrate intoxication: hypocalcemia, hypotension, narrowed pulse pressure, increased end-diastolic pressure • Cardiovascular depression can occur if transfusion rate > 1 unit of blood per 5 mins • Risk factors: hypothermia, liver disease, liver transplantation

15. Fresh Frozen Plasma • Portion of whole blood that remains after cellular elements and platelets are removed • Each unit contains 250cc plasma • Contains coagulating factors and fibrinogen • Increases level of each clotting factor by 2-3% • Needs to be ABO-compatible but does not require crossmatching Rh typing

16. Fresh Frozen Plasma • Indications: • 1) urgent reversal of Warfarin therapy • 2) correction of isolated coagulation factor deficiencies • 3) correction of microvascular bleeding when INR and pTT >1.5 x normal • 4) correction of microvascular bleeding due to coagulation factor deficiency in patients transfused with > one blood volume and when PT and pTT can not be obtained • 5) Antithrombin III deficiency • 6) Treatment of immunodeficiencies • 7) Treatment of thrombotic thrombocytopenia purpura

17. Platelets • Indicated for thrombocytopenia platelet count < 50 x 109/L • Pooled from donated blood (ie. 5 donors=5000 plt/microL) • Each 10-12 units of pRBC decrease plt count by 50%, for replacement therapy, 5-10 units of plt (ie. 5000 – 10 000 plt/microL) should be given when 10-20 units of pRBC has been transfused • Transfuse SLOWLY to avoid hypotension

18. Cryoprecipitate • Collected by thawing FFP at 40C, contains von Willebrand factor, factor VIII, XIII, fibrinogen, and fibronectin • One unit of cryoprecipitate will increase fibrinogen concentration by 50mg/dL • Indicatation: • Patients with von Willebrand’s Dz unresponsive to Desmopressin • Bleeding patients with vWD • Bleeding patients with fibrinogen levels < 80-100mg/dL • Hemophilia A • Administer rapidly through a filter (ie. 200 cc/hr, infusion should be completed within 6 hrs of thawing)

19. Coagulation Cascade PT/INR aPTT Image from: http://www.aafp.org/afp/20010801/419_f1.gif

20. Pathophysiology of Coagulopathy in Massive Transfusions Coagulopathy results from: • hemodilution • hypothermia • unfractionated blood products • DIC

21. Hemodilution • Crystalloids -1/4 stays intravascularly, 3/4 goes into interstium -Dilute platelet and coagulating factors • Colloids -Hespan and Dextran impair platelet adhesion by decreasing von Willebrand factor activity -Impair thrombin and clot formation

22. Hypothermia Hypothermia (<35 degrees): • slows activity of coagulation cascade • reduces synthesis of coagulation factors • increase fibrinolysis • decrease platelets and affects platelet function • Hypothermia and acidosis cause significant bleeding despite adequate blood, plasma and plt replacement

23. Blood Components • Red Blood Cells-contribute to thrombosis and hemostasis -Contain ADP that activates platelets, activate platelet cyclooxygenase, increase generation of thromboxane A2, increase thrombin -Abnormalities of Prothrombin time (PT) and activated partial thromboplastin time (aPTT) occur after transfusion of 12 units of pRBC • Coagulation Factors-Blood loss greater than EBVx2 resulted in deficiency of prothrombin, factor V, factor VII, and platelets • Platelet- Thrombocytopenia occur after transfusion of 20 units of pRBC

24. Disseminated Intravascular Coagulation • An acquired syndrome secondary to systemic and excessive activation of coagulation. • Tissue trauma, brain injury, shock, tissue anoxia, hypothermia contribute to DIC • Diagnosis: D-dimer>500mcg/L, increased INR, thrombocytopenia, microvascular bleeding +/- thrombosis • Risk factors: acidosis, hypothermia, hypotension, increase in injury severity

25. Transfusion Service Protocol at Parkland Memorial Hospital, Texas • Cooperative effort between Pathology, Anesthesiology and Trauma Surgery • Goal: to support rapid transfusion in ER and OR with regular shipments of blood products released automatically on a timed basis • Design for massive transfusion protocol is based on patterns of coagulopathy that may develop during trauma care • Patient survival to date appox. 50% with the protocol

26. Transfusion Service Protocol

27. Human Recombinant Factor VIIa • Vitamin K-dependent glycoprotein • Indications: treatment of bleeding in hemophilia A and B, acquired inhibitors (e.g. anti-VIII), and congenital factor VII deficiency bleeding • Site of action: extrinsic coagulation cascade • Promotes activation of factor X to Xa, and factor II (prothrombin) to IIa (thrombin) - bypassing the intrinsic pathway • Promotes clot formation and hemostasis at the site of injury • Shorten the prothrombin time (PT) • Extent of PT shortening does not correlate with clinical efficacy of rFVIIa → need for monitoring blood loss, transfusion requirement, and hemoglobin Image from: www.itxm.org/images/coag1.jpg

28. Human Recombinant Factor VIIa • Efficacious adjuvant therapy in managing hemorrhage due to trauma • Reduce the need for massive blood transfusions in blunt trauma • No increased risk for thromboembolic event, DIC, allergic rxn or thrombocytopenia • Reduced risk assoc. with plasma transmission of virus • Less frequent complications associated with microthrombus generations such as multi-organ failure and ARDS • Frequent dosing needed due to short half-life (2-3hrs) • Recommended dose: 90 mg/kg, continued every 2-3 hours. Once bleeding and hemoglobin have stabilized, taper to every 6-8 hours, then every 12-24 hours, and then stop

29. Management of Coagulopathy in Massive Transfusions • Maintain core body temp > 35oC • Correct Acidosis by re-establishing adequate tissue perfusion and oxygenation • Check labs (ie. ABGs, lytes, coags, plt, fibrinogen, lactate) • Replete electrolytes (ie. Calcium) • Early administration of FFP and platelets during massive transfusion with pRBC Stay ahead of the game to prevent coagulopathy in the first instance