Massive Transfusion And Massive Transfusion And CoagulopathyCoagulopathy

Christine Mai, MDChristine Mai, MDFaculty Advisor: Mauricio Gonzalez, MDFaculty Advisor: Mauricio Gonzalez, MD

Department of AnesthesiologyDepartment of AnesthesiologyBoston University Medical CenterBoston University Medical Center

Guidelines to Blood Product Guidelines to Blood Product TransfusionsTransfusions

In 1994, the ASA established the Task Force on In 1994, the ASA established the Task Force on Blood Component Therapy to develop evidence-Blood Component Therapy to develop evidence-based guidelines for transfusing blood products in based guidelines for transfusing blood products in perioperative and peripartum settingsperioperative and peripartum settings

22 million blood components transfused yearly22 million blood components transfused yearly Benefits: improved tissue oxygenation and decreased Benefits: improved tissue oxygenation and decreased

bleeding bleeding Risks: Transmission of infectious diseases, Risks: Transmission of infectious diseases,

hemolytic and nonhemolytic transfusion reactions, hemolytic and nonhemolytic transfusion reactions, immunosuppression, alloimmunization, coagulopathyimmunosuppression, alloimmunization, coagulopathy

Massive TransfusionMassive Transfusion

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

American College of Surgeon’s Classes of Acute HemorrhageAmerican College of Surgeon’s Classes of Acute Hemorrhage

ClassClass II IIII IIIIII IVIV

Blood loss (ml)Blood loss (ml) ≤≤750750 750-1500750-1500 1500-20001500-2000 ≥ ≥ 20002000

Blood loss (% Blood loss (% blood volume)blood volume)

≤≤15%15% 15-30%15-30% 30-40%30-40% ≥≥40%40%

Pulse ratePulse rate <100<100 >100>100 >120>120 ≥ ≥ 140140

Blood pressureBlood pressure NormalNormal Normal Normal DecreasedDecreased DecreasedDecreased

Pulse pressure Pulse pressure (mmHg)(mmHg)

Normal or Normal or increasedincreased

DecreasedDecreased DecreasedDecreased DecreasedDecreased

Capillary refill Capillary refill testtest

NormalNormal PositivePositive PositivePositive PositivePositive

Respiratory rateRespiratory rate 14-2014-20 20-3020-30 30-4030-40 >35>35

Urine output Urine output (ml/hr)(ml/hr)

≥ ≥ 3030 20-3020-30 5-155-15 NegligibleNegligible

CNS-mental CNS-mental statusstatus

Slightly anxiousSlightly anxious Mildly anxiousMildly anxious Anxious and Anxious and confusedconfused

Confused, Confused, lethargiclethargic

Fluid replacement Fluid replacement (3:1 rule)(3:1 rule)

CrystalloidCrystalloid CrystalloidCrystalloid Crystalloid + Crystalloid + BloodBlood

Crystalloid + Crystalloid + BloodBlood

Parameters For Fluid ReplacementParameters For Fluid Replacement

MaintenanceMaintenance DeficitsDeficits Insensible lossInsensible loss Estimated blood lossEstimated blood loss

MaintenanceMaintenance 4:2:1 Rule or Calculate Wt +40 cc4:2:1 Rule or Calculate Wt +40 cc Calculated weight: (IBW + ABW)/2Calculated weight: (IBW + ABW)/2 IBW male: 110 lbs + 7 lbs * in > 5’IBW male: 110 lbs + 7 lbs * in > 5’

female: 100 lbs + 6 lbs * in > 5’female: 100 lbs + 6 lbs * in > 5’

DeficitsDeficits NPO statusNPO status

Calculated Wt x hrs NPO x 0.7Calculated Wt x hrs NPO x 0.7 Bowel prep ~ 1200ccBowel prep ~ 1200cc Diuretics/ Urine outputDiuretics/ Urine output NGT drainageNGT drainage CT drainageCT drainage

Insensible LossInsensible Loss

Case TypeCase Type VolumeVolume

Non-openNon-open 2-3 cc/kg/hr 2-3 cc/kg/hr

OpenOpen 4-6 cc/kg/hr 4-6 cc/kg/hr

Major Abdominal 6-10 cc/kg/hrMajor Abdominal 6-10 cc/kg/hr

TraumaTrauma > 10 cc/kg/hr > 10 cc/kg/hr

(Volume based on Calculated Weight)(Volume based on Calculated Weight)

Estimated Blood LossEstimated Blood Loss The 3: 1 Rule, replace 3 cc crystalloid : 1 The 3: 1 Rule, replace 3 cc crystalloid : 1

cc blood losscc blood loss The 1:1 Rule, replace 1 cc colloid : 1 cc The 1:1 Rule, replace 1 cc colloid : 1 cc

blood lossblood loss

Allowable Blood LossAllowable Blood Loss((Hct present - Hct allowableHct present - Hct allowable) + EBV) + EBV

Hct present Hct present

Estimated Blood Estimated Blood VolumeVolume

Adults: 75 cc/kgAdults: 75 cc/kgInfants: 80 cc/kgInfants: 80 cc/kgNeonates: 85cc/kgNeonates: 85cc/kg

Fluid Resuscitation CrystalloidsFluid Resuscitation Crystalloids

Na Na (mEq)(mEq)

Cl Cl (mEq)(mEq)

K K (mEq)(mEq)

Ca Ca (mEq)(mEq)

Mg Mg (mEq)(mEq)

LactateLactate AcetateAcetate GluconateGluconate pHpH mOsmmOsm OtherOther

NS NS (0.9%)(0.9%)

154154 154154 5.05.0 308308 Indicated in Indicated in neurosugery neurosugery casescases

LRLR 130130 109109 44 2.72.7 2828 6.56.5 273273 Contraindicated Contraindicated in liver and in liver and kidney failurekidney failure

PLPL 140140 9898 55 33 2727 2323 7.47.4 294294 PhysiologicPhysiologic pHpH

Type and ScreenType and Screen Screen for ABO-Rh type and most common antibodiesScreen for ABO-Rh type and most common antibodies ABO incompatibility is a tragic and severe reaction, resulting ABO incompatibility is a tragic and severe reaction, resulting

in rapid intravenous hemolysisin rapid intravenous hemolysis Ordered during elective cases when the probability of blood Ordered during elective cases when the probability of blood

loss and transfusion are highloss and transfusion are high If blood is needed for emergent transfusion, a crossmatch can If blood is needed for emergent transfusion, a crossmatch can

be performed to reconfirm ABO-Rh typingbe performed to reconfirm ABO-Rh typing Reactions against lower-incident antigens may still occur Reactions against lower-incident antigens may still occur

Emergency trauma cases: Type O Rh-Negative (Universal Emergency trauma cases: Type O Rh-Negative (Universal Donor) Uncrossmatched Blood transfused until a Type and Donor) Uncrossmatched Blood transfused until a Type and Cross clot is testedCross clot is tested

Type and Crossmatching Type and Crossmatching CrossmatchingCrossmatching

-Trial transfusion within a test tube between donor RBCs and recipient serum to -Trial transfusion within a test tube between donor RBCs and recipient serum to detect a potential for serious transfusion reaction detect a potential for serious transfusion reaction - 3 Phases:- 3 Phases: -Reconfirm ABO-Rh typing-Reconfirm ABO-Rh typing- Detect antibodies that are incomplete or do not agglutinate - Detect antibodies that are incomplete or do not agglutinate easily easily - Detect antibodies in other blood group systems (ie. Rh, Kell, - Detect antibodies in other blood group systems (ie. Rh, Kell, Kidd, Duffy) Kidd, Duffy)

Antibody screeningAntibody screening- Trial transfusion between the recipient’s serum and commercially supplied Trial transfusion between the recipient’s serum and commercially supplied

RBCs with antigens that will react with antibodies commonly implicated in RBCs with antigens that will react with antibodies commonly implicated in non-ABO hemolytic transfusion reactions non-ABO hemolytic transfusion reactions

- Donor’s serum also screened for unexpected antibodies to prevent their Donor’s serum also screened for unexpected antibodies to prevent their introduction to the recipient’s serumintroduction to the recipient’s serum

- Otherwise known as the Coomb’s test.Otherwise known as the Coomb’s test.

Blood Products TransfusionBlood Products Transfusion

Packed Red Blood CellsPacked Red Blood Cells Fresh Frozen PlasmaFresh Frozen Plasma PlateletsPlatelets CryoprecipitateCryoprecipitate

Packed Red Blood CellsPacked Red Blood Cells Approx. 12 000 000 units of RBC are transfused yearly in the USApprox. 12 000 000 units of RBC are transfused yearly in the US Indicated for patients needing red cells for oxygen carrying Indicated for patients needing red cells for oxygen carrying

capacity rather than for volume replacement (ie. CHF patients)capacity rather than for volume replacement (ie. CHF patients) 70% Hct in pRBC compared to 40% Hct in whole blood70% Hct in pRBC compared to 40% Hct in whole blood Each unit contains 250-350 cc of red cells, increases Hct 3-4% or Each unit contains 250-350 cc of red cells, increases Hct 3-4% or

increases Hgb 1g/dLincreases Hgb 1g/dL Large amount of transfusions should be warmed to 37Large amount of transfusions should be warmed to 3700CC Dilute pRBCs with either normal saline or plasmalyte when Dilute pRBCs with either normal saline or plasmalyte when

giving massive transfusionsgiving massive transfusions Avoid Lactated Ringers because calcium can chealate with citrate Avoid Lactated Ringers because calcium can chealate with citrate

Citrate ToxicityCitrate Toxicity

Calcium binding to citrate preservative in Calcium binding to citrate preservative in transfused blood transfused blood → → Hypocalcemia Hypocalcemia

Signs of citrate intoxication: hypocalcemia, Signs of citrate intoxication: hypocalcemia, hypotension, narrowed pulse pressure, hypotension, narrowed pulse pressure, increased end-diastolic pressureincreased end-diastolic pressure

Cardiovascular depression can occur if Cardiovascular depression can occur if transfusion rate > 1 unit of blood per 5 minstransfusion rate > 1 unit of blood per 5 mins

Risk factors: hypothermia, liver disease, liver Risk factors: hypothermia, liver disease, liver transplantationtransplantation

Fresh Frozen PlasmaFresh Frozen Plasma Portion of whole blood Portion of whole blood

that remains after cellular that remains after cellular elements and platelets are elements and platelets are removedremoved

Each unit contains 250cc Each unit contains 250cc plasmaplasma

Contains coagulating Contains coagulating factors and fibrinogenfactors and fibrinogen

Increases level of each Increases level of each clotting factor by 2-3%clotting factor by 2-3%

Needs to be ABO-Needs to be ABO-compatible but does not compatible but does not require crossmatching Rh require crossmatching Rh typingtyping

Fresh Frozen PlasmaFresh Frozen Plasma

Indications: Indications: 1) urgent reversal of Warfarin therapy1) urgent reversal of Warfarin therapy2) correction of isolated coagulation factor deficiencies2) correction of isolated coagulation factor deficiencies3) correction of microvascular bleeding when INR and 3) correction of microvascular bleeding when INR and pTT >1.5 x normalpTT >1.5 x normal4) correction of microvascular bleeding due to 4) correction of microvascular bleeding due to coagulation factor deficiency in patients transfused with coagulation factor deficiency in patients transfused with > one blood volume and when PT and pTT can not be > one blood volume and when PT and pTT can not be obtainedobtained

5) Antithrombin III deficiency5) Antithrombin III deficiency 6) Treatment of immunodeficiencies6) Treatment of immunodeficiencies 7) Treatment of thrombotic thrombocytopenia purpura7) Treatment of thrombotic thrombocytopenia purpura

PlateletsPlatelets

Indicated for thrombocytopenia platelet count < 50 x 10Indicated for thrombocytopenia platelet count < 50 x 1099/L/L Pooled from donated blood (ie. 5 donors=5000 plt/microL)Pooled from donated blood (ie. 5 donors=5000 plt/microL) Each 10-12 units of pRBC decrease plt count by 50%, for Each 10-12 units of pRBC decrease plt count by 50%, for

replacement therapy, 5-10 units of plt (ie. 5000 – 10 000 replacement therapy, 5-10 units of plt (ie. 5000 – 10 000 plt/microL) should be given when 10-20 units of pRBC has plt/microL) should be given when 10-20 units of pRBC has been transfusedbeen transfused

Transfuse SLOWLY to avoid hypotensionTransfuse SLOWLY to avoid hypotension

CryoprecipitateCryoprecipitate

Collected by thawing FFP at 4Collected by thawing FFP at 400C, contains von Willebrand C, contains von Willebrand factor, factor VIII, XIII, fibrinogen, and fibronectinfactor, factor VIII, XIII, fibrinogen, and fibronectin

One unit of cryoprecipitate will increase fibrinogen One unit of cryoprecipitate will increase fibrinogen concentration by 50mg/dLconcentration by 50mg/dL

Indicatation:Indicatation: Patients with von Willebrand’s Dz unresponsive to DesmopressinPatients with von Willebrand’s Dz unresponsive to Desmopressin Bleeding patients with vWDBleeding patients with vWD Bleeding patients with fibrinogen levels < 80-100mg/dLBleeding patients with fibrinogen levels < 80-100mg/dL Hemophilia AHemophilia A

Administer rapidly through a filter (ie. 200 cc/hr, infusion Administer rapidly through a filter (ie. 200 cc/hr, infusion should be completed within 6 hrs of thawing)should be completed within 6 hrs of thawing)

Coagulation CascadeCoagulation Cascade

Pathophysiology of Coagulopathy in Pathophysiology of Coagulopathy in Massive TransfusionsMassive Transfusions

Coagulopathy results from:Coagulopathy results from: hemodilutionhemodilution hypothermiahypothermia unfractionated blood products unfractionated blood products DICDIC

HemodilutionHemodilution

CrystalloidsCrystalloids

-1/4 stays intravascularly, 3/4 -1/4 stays intravascularly, 3/4 goes into interstiumgoes into interstium

-Dilute platelet and coagulating -Dilute platelet and coagulating factorsfactors

ColloidsColloids-Hespan and Dextran impair -Hespan and Dextran impair platelet adhesion by decreasing platelet adhesion by decreasing von Willebrand factor activityvon Willebrand factor activity

-Impair thrombin and clot -Impair thrombin and clot formationformation

HypothermiaHypothermiaHypothermia (<35 degrees): Hypothermia (<35 degrees): slows activity of coagulation cascadeslows activity of coagulation cascade reduces synthesis of coagulation factorsreduces synthesis of coagulation factors increase fibrinolysisincrease fibrinolysis decrease platelets and affects platelet decrease platelets and affects platelet

functionfunction Hypothermia and acidosis cause Hypothermia and acidosis cause

significant bleeding despite adequate significant bleeding despite adequate blood, plasma and plt replacementblood, plasma and plt replacement

Blood ComponentsBlood Components

Red Blood Cells-contribute to thrombosis and hemostasisRed Blood Cells-contribute to thrombosis and hemostasis-Contain ADP that activates platelets, activate platelet -Contain ADP that activates platelets, activate platelet cyclooxygenase, increase generation of thromboxane A2, cyclooxygenase, increase generation of thromboxane A2, increase thrombinincrease thrombin-Abnormalities of Prothrombin time (PT) and activated -Abnormalities of Prothrombin time (PT) and activated partial thromboplastin time (aPTT) occur after transfusion partial thromboplastin time (aPTT) occur after transfusion of 12 units of pRBCof 12 units of pRBC

Coagulation Factors-Blood loss greater than EBVx2 Coagulation Factors-Blood loss greater than EBVx2 resulted in deficiency of prothrombin, factor V, factor VII, resulted in deficiency of prothrombin, factor V, factor VII, and plateletsand platelets

Platelet- Thrombocytopenia occur after transfusion of 20 Platelet- Thrombocytopenia occur after transfusion of 20 units of pRBCunits of pRBC

Disseminated Intravascular Disseminated Intravascular CoagulationCoagulation

An acquired syndrome secondary to systemic and excessive An acquired syndrome secondary to systemic and excessive activation of coagulation. activation of coagulation.

Tissue trauma, brain injury, shock, tissue anoxia, Tissue trauma, brain injury, shock, tissue anoxia, hypothermia contribute to DIChypothermia contribute to DIC

Diagnosis: D-dimer>500mcg/L, increased INR, Diagnosis: D-dimer>500mcg/L, increased INR, thrombocytopenia, microvascular bleeding +/- thrombosisthrombocytopenia, microvascular bleeding +/- thrombosis

Risk factors: acidosis, hypothermia, hypotension, increase in Risk factors: acidosis, hypothermia, hypotension, increase in injury severityinjury severity

Transfusion Service Protocol at Transfusion Service Protocol at Parkland Memorial Hospital, TexasParkland Memorial Hospital, Texas

Cooperative effort between Pathology, Anesthesiology Cooperative effort between Pathology, Anesthesiology and Trauma Surgeryand Trauma Surgery

Goal: to support rapid transfusion in ER and OR with Goal: to support rapid transfusion in ER and OR with regular shipments of blood products released regular shipments of blood products released automatically on a timed basisautomatically on a timed basis

Design for massive transfusion protocol is based on Design for massive transfusion protocol is based on patterns of coagulopathy that may develop during trauma patterns of coagulopathy that may develop during trauma carecare

Patient survival to date appox. 50% with the protocolPatient survival to date appox. 50% with the protocol

Transfusion Service ProtocolTransfusion Service Protocol

ShipmentsShipments #1#1 #2#2 #3#3 #4#4

5 units pRBC + 5 units pRBC + 2 units FFP 2 units FFP q30minsq30mins

XX XX XX XX

Platelets (5 Platelets (5 pooled units)pooled units)

XX XX

CryoprecipitateCryoprecipitate

(10 pooled unit)(10 pooled unit)XX

rFVIIarFVIIa

(sent at pRBC (sent at pRBC units 11-15)units 11-15)

XX

Human Recombinant Factor VIIaHuman Recombinant Factor VIIa Vitamin K-dependent glycoprotein Vitamin K-dependent glycoprotein Indications: treatment of bleeding in Indications: treatment of bleeding in

hemophilia A and B, acquired hemophilia A and B, acquired inhibitors (e.g. anti-VIII), and inhibitors (e.g. anti-VIII), and congenital factor VII deficiency congenital factor VII deficiency bleeding bleeding

Site of action: extrinsic coagulation Site of action: extrinsic coagulation cascadecascade

Promotes activation of factor X to Xa, Promotes activation of factor X to Xa, and factor II (prothrombin) to IIa and factor II (prothrombin) to IIa (thrombin) - bypassing the intrinsic (thrombin) - bypassing the intrinsic pathwaypathway

Promotes clot formation and Promotes clot formation and hemostasis at the site of injury hemostasis at the site of injury

Shorten the prothrombin time (PT)Shorten the prothrombin time (PT) Extent of PT shortening does not Extent of PT shortening does not

correlate with clinical efficacy of correlate with clinical efficacy of rFVIIa rFVIIa → need for→ need for monitoring blood monitoring blood loss, transfusion requirement, and loss, transfusion requirement, and hemoglobinhemoglobin

Image from: www.itxm.org/images/coag1.jpg

Human Recombinant Factor VIIaHuman Recombinant Factor VIIa

Efficacious adjuvant therapy in managing hemorrhage due to Efficacious adjuvant therapy in managing hemorrhage due to trauma trauma

Reduce the need for massive blood transfusions in blunt traumaReduce the need for massive blood transfusions in blunt trauma No increased risk for thromboembolic event, DIC, allergic rxn No increased risk for thromboembolic event, DIC, allergic rxn

or thrombocytopeniaor thrombocytopenia Reduced risk assoc. with plasma transmission of virusReduced risk assoc. with plasma transmission of virus Less frequent complications associated with microthrombus Less frequent complications associated with microthrombus

generations such as multi-organ failure and ARDSgenerations such as multi-organ failure and ARDS Frequent dosing needed due to short half-life (2-3hrs)Frequent dosing needed due to short half-life (2-3hrs) Recommended dose: 90 mg/kg, continued every 2-3 hours. Recommended dose: 90 mg/kg, continued every 2-3 hours.

Once bleeding and hemoglobin have stabilized, taper to every Once bleeding and hemoglobin have stabilized, taper to every 6-8 hours, then every 12-24 hours, and then stop6-8 hours, then every 12-24 hours, and then stop

Management of Coagulopathy in Management of Coagulopathy in Massive TransfusionsMassive Transfusions

Maintain core body temp > 35Maintain core body temp > 35ooCC Correct Acidosis by re-establishing adequate tissue perfusion Correct Acidosis by re-establishing adequate tissue perfusion

and oxygenationand oxygenation Check labs (ie. ABGs, lytes, coags, plt, fibrinogen, lactate)Check labs (ie. ABGs, lytes, coags, plt, fibrinogen, lactate) Replete electrolytes (ie. Calcium)Replete electrolytes (ie. Calcium) Early administration of FFP and platelets during massive Early administration of FFP and platelets during massive

transfusion with pRBCtransfusion with pRBC

Stay ahead of the game to prevent coagulopathy Stay ahead of the game to prevent coagulopathy in the first instancein the first instance