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Massive Transfusion And Coagulopathy

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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
II III IV Blood loss (ml) ≤750 ≥ 2000 Blood loss (% blood volume) ≤15% 15-30% 30-40% ≥40% Pulse rate <100 >100 >120 ≥ 140 Blood pressure Normal Decreased Pulse pressure (mmHg) Normal or increased Capillary refill test Positive Respiratory rate 14-20 20-30 30-40 >35 Urine output (ml/hr) ≥ 30 5-15 Negligible CNS-mental status Slightly anxious Mildly anxious Anxious and confused Confused, lethargic Fluid replacement (3:1 rule) Crystalloid Crystalloid + Blood

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

6 Maintenance Deficits 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 Type Volume Non-open 2-3 cc/kg/hr
Major Abdominal cc/kg/hr Trauma > 10 cc/kg/hr (Volume based on Calculated Weight)

8 Estimated Blood Volume
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
Na (mEq) Cl (mEq) K (mEq) Ca (mEq) Mg (mEq) Lactate Acetate Gluconate pH mOsm Other NS (0.9%) 154 5.0 308 Indicated in neurosugery cases LR 130 109 4 2.7 28 6.5 273 Contraindicated in liver and kidney failure PL 140 98 5 3 27 23 7.4 294 Physiologic pH

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
-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 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 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 units of pRBC decrease plt count by 50%, for replacement therapy, 5-10 units of plt (ie – plt/microL) should be given when 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 < mg/dL Hemophilia A Administer rapidly through a filter (ie. 200 cc/hr, infusion should be completed within 6 hrs of thawing)

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

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
Shipments #1 #2 #3 #4 5 units pRBC + 2 units FFP q30mins X Platelets (5 pooled units) Cryoprecipitate (10 pooled unit) rFVIIa (sent at pRBC units 11-15)

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:

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 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


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