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Massive Transfusion And Coagulopathy. Christine Mai, MD Faculty Advisor: Mauricio Gonzalez, MD Department of Anesthesiology Boston University Medical Center. Guidelines to Blood Product Transfusions.

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massive transfusion and coagulopathy

Massive Transfusion And Coagulopathy

Christine Mai, MD

Faculty Advisor: Mauricio Gonzalez, MD

Department of Anesthesiology

Boston University Medical Center

guidelines to blood product transfusions
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
massive transfusion
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

parameters for fluid replacement
Parameters For Fluid Replacement
  • Maintenance
  • Deficits
  • Insensible loss
  • Estimated blood loss
  • 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’


  • NPO status

Calculated Wt x hrs NPO x 0.7

  • Bowel prep ~ 1200cc
  • Diuretics/ Urine output
  • NGT drainage
  • CT drainage
insensible loss
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)

estimated blood loss
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

type and screen
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
type and crossmatching
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


- 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.
blood products transfusion
Blood Products Transfusion
  • Packed Red Blood Cells
  • Fresh Frozen Plasma
  • Platelets
  • Cryoprecipitate
packed red blood cells
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
citrate toxicity
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
fresh frozen plasma
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
fresh frozen plasma16
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
  • 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
  • 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)
coagulation cascade
Coagulation Cascade



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pathophysiology of coagulopathy in massive transfusions
Pathophysiology of Coagulopathy in Massive Transfusions

Coagulopathy results from:

  • hemodilution
  • hypothermia
  • unfractionated blood products
  • DIC
  • 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


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
blood components
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
disseminated intravascular coagulation
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
transfusion service protocol at parkland memorial hospital texas
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
human recombinant factor viia
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

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human recombinant factor viia28
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
management of coagulopathy in massive transfusions
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