Modern Transfusion Management in Cardiovascular Surgery

Linda Shore-Lesserson, M.D.,Professor of AnesthesiologyAlbert Einstein School of MedicineMontefiore Medical CenterBronx, New York,

Patient Blood Management

• Multidisciplinary interaction• Three pillars of management

i i i i f d ll– Preoperative optimization of red cell mass– Perioperative reduction in red cell lossPerioperative reduction in red cell loss– Perioperative optimal treatment of anemia

Patient Blood Management- CT SurgeryPreop Blood Conservation Treat Anemia

AnesthAnesthAnesth

SurgAnesth

SurgSurgMed/Card

ICUPerf

Patient Blood Management CT SurgeryPreop Blood Conservation Treat Anemia

Patient Blood Management- CT Surgeryp

AnesthAnesth Anesth

SurgS

SurgSurg

Med/CardCard

ICUPerf

Annals of Thoracic Surgery 2007;83:S27-86

T f i Ri kTransfusion RisksPublic concern:Public concern:transmissible diseases

NAT- 1999 Pre- NAT Post-NAT

Hepatitis C 1:237,000 <1:1,000,000

Hepatitis B 1:137,000

HIV 1:1,326,300 1:1,930,000

HTLV I and II 1:641,000

C t i ti R tContamination Rates(1996 reported) Contamination

RBC’s (1:500,000) 1:38,565

Apheresis platelets 1:777

Random donor plt (1:12,000) 1:3254

Random donor /6-pack 1:542

Sandler SG: Clin Adv Hematol Oncol 2003;1:307-313

Transfusion RisksTransfusion RisksPhysician concerns:Physician concerns:White Blood Cell Effects

• Antibody formation• Febrile reactions• GVHD• Volume overload (TACO)• Volume overload (TACO)• Lung injury (1/5000)• Graft survival• Cancer recurrence• Infection

O i i i f CPre- Optimization of RBC Mass

• Erythropoietin is reasonable to restore red cell l h PAD i dvolume preop when PAD is used.

– Class IIa, Level A IIb

G ldb MA P i i l f d i d•Goldberg MA: Perioperative epo: results of randomized clinical trials. Semin Hematol 1997;34:41–7Al h di AA A i i d l i•Alghamdi AA: A systematic review and meta-analysis.

J Card Surg 2006;21:320–6

Bl d C ti Ph lBlood Conservation- Pharmacology

• Antifibrinolytics (aprotinin, EACA, TA) are indicated to reduce the # patients transfused, andindicated to reduce the # patients transfused, and to reduce blood loss after cardiac operations

Cl I L l A A ti i Cl 3 L l A– Class I, Level A Aprotinin- Class 3, Level A• Use of rVIIa is not unreasonable for the

management of intractable nonsurgical bleeding unresponsive to routine hemostatic therapy afterunresponsive to routine hemostatic therapy after cardiac …

Cl IIb L l B h– Class IIb, Level B no change

Antifibrinolytic Agents MOAAntifibrinolytic Agents- MOAKallikrein Aprotinin

XIIIXL fibrin

Aprotinin

IIaXL fibrin

XIIIaPltPlt

Meta-AnalysisMeta Analysis

T f iTransfusionAprotinin

EACA/TA

Re-explorationAprotininAprotinin

EACA/TADecreased Risk Increased Risk

0.1 1 10

Levi et al: Lancet 1999;354:1940-47

Factor VIIa and Tube DrainageFactor VIIa and Tube Drainage

Karkouti: Transfusion 2005;45:26-34

rVIIa and Matched ControlsAll demo = rVIIa Controls P value

RBC (U) 14 (9 18) 7 (3 13) 0 0001RBCs (U) 14 (9,18) 7 (3,13) <0.0001

Plts (U) 15 (10,20) 5 (0,15) <0.0001

LOS ICU 6(3.5,11.5) 3.5 (1,10) <0.05

Renal dys (%) 15(29) 6 (12) <0.05

Karkouti: Transfusion 2005;45:26-34

C di R i Off L b l UCanadian Review: Off-Label Use

• Multicenter, observational, retrospective (n=503)J 1 2003 D b 31 2006 di• Jan 1, 2003-December 31, 2006: cardiac surgery

• Blood bank, pharmacy, hospital recordsp y p– Use of rVIIa, response to rVIIa

Transfusion before and after rVIIa– Transfusion before and after rVIIa– Adverse outcomes

• Comparison cohort used (2004 data, 7 centers)

Karkouti: Circulation 2008;118:331-338

R ltResultsV i bl B f VII Aft VII lVariable Before rVIIa After rVIIa p value

RBCs 8(5,12) 2(1,5) <0.0001Cs ( , ) ( , ) .

Plts 10(10,15) 5(0,10) <0.0001( ) ( )

FFP 8(5 12) 2(0 6) <0 0001FFP 8(5,12) 2(0,6) <0.0001

Total 33(22,50) 9(2,22) <0.0001

Karkouti: Circulation 2008;118:331-338

Independent Predictors MortalityIndependent Predictors Mortality

Variable OR 95% CI p

Preop shock 2.7 1.5-4.9 0.0009

pH<7 2 pre Rx 7 9 2 7-23 3 0 0003pH<7.2 pre Rx 7.9 2.7-23.3 0.0003

RBCs >10 pre 2.4 1.4-4.0 0.0008

RBCs >10 post 8.9 3.6-22.0 0.0001

Renal dysfx, age unstable CPB dur <0.03

Karkouti: Circulation 2008;118:331-338

l d C i h lBlood Conservation-Pharmacology• DDAVP is not unreasonable to attenuate excess

bleeding and transfusion in certain patients withbleeding and transfusion in certain patients with demonstrable platelet dysfunction known to respond to this agentrespond to this agent– Class IIb, Level B

• Routine use of prophylactic DDAVP is not recommended to reduce bleeding or bloodrecommended to reduce bleeding or blood transfusion after cardiac operations…

Cl III L l A– Class III, Level A

Bl d C i Ph lBlood Conservation- Pharmacology• D/C thienopyridine agents 5-7d

– Class IIa, Level B,

• D/C thienopyridines as short as 3 d• D/C thienopyridines as short as 3 d– Class I, Level BD/C i i i l l i• D/C aspirin in purely elective cases– Class IIa, Level A

• Heparin-protamine managementClass IIb Level B– Class IIb, Level B

CPB-Platelet Effects

ThrombinThrombinThrombin receptor

ADPGpIIb/IIIaGpIIb/IIIaGpIIb/IIIa AggregationGpIIb/IIIaGpIIb/IIIa Aggregation

PlateletAdhesion

Epinephrine

Endothelium

vWF

Exposed Collagen

Endothelium

h C f CA G?What Can Be Done for CABG?

• Wait a few days! Measure plt inhibition*D it ff !• Do it off-pump!

• If you must proceed on CPBIf you must proceed on CPB– Measure preop plt inhibition*

ifib i l i– Use antifibrinolytic?– POC coag testing for tx algorithm– DDAVP esp if plts are transfused

*R i M t l A Th S 2011 91 123 130*Ranucci M et al: Ann Thorac Surg 2011;91:123-130

Off Pump Cardiac SurgeryOff Pump Cardiac SurgeryClass IIa, Level A,

Cheng et al: Anesthsiology 2005;102:199-203

Clopidogrel and Off-Pump CABG

• Database OPCAB January 2000-June 2002• Excluded

– Emergency, salvage, mini-incision, other proc, g y, g , , p ,preop anticoagulants, anti-GPIIbIIIa, TPA

• N=1572, clop (n=281), none (n=1291)N 1572, clop (n 281), none (n 1291)• Clopidogrel <7 days vs. none

N b li d hi diff MI• No baseline demographic differences exc MI

Kapetanakis EI: Circulation 2006;113:1667-74

Clopidogrel and Off-Pump CABG

Clop None p

I t RBC % 22 0 16 0 <0 01Intraop RBC % 22.0 16.0 <0.01

Intraop Plts % 3.2 1.0 <0.01Intraop Plts % 3.2 1.0 0.01

Postop RBC % 55.9 34.4 <0.01

Reop % 6.4 1.4 <0.01

LOS days 5 4 0.03

Kapetanakis EI: Circulation 2006;113:1667-74

Bl d C i T h l iBlood Conservation- Technologic

• Red cell salvageCl I L l A– Class I, Level A

• Centrifugal pumps– Class IIb, Level B

• Heparin-coated circuits (+/- low heparin)Heparin coated circuits (+/ low heparin)– Class IIb, Level B

• PRP ith adeq ate plt ield• PRP with adequate plt yield– Class III, Level A Class IIa

P i ti T t t f A iPerioperative Treatment of Anemia

• Hb<6 g/dL: RBC tx is reasonable-can be lifesaving- Level IIa, Class Clifesaving Level IIa, Class C

• Hb<7g/dL: RBC tx is reasonable in most i b hi h l l idpostop patients but no high-level evidence

– Level IIa, Class C• Hb>10g/dL: RBC tx is not unreasonable in

patients with critical noncardiac end organpatients with critical noncardiac end-organ ischemia (eg, CNS and gut)– Level IIb, Class C

f i i i CTransfusion Triggers During CPB• Hb<6 g/dL: RBC tx is reasonable-except in pts

at risk for decreased cerebral oxygen deliveryyg y• Hb>6g/dL: RBC tx is reasonable depending on

patient factors SVO2 etcpatient factors, SVO2, etc.– Level IIa, Class C

• Hb<7g/dL: RBC tx is not unreasonable in patients with critical noncardiac end-organpatients with critical noncardiac end organ ischemia (eg, CNS and gut)

L l IIb Cl C– Level IIb, Class C

C f iNon-RBC Transfusion

• It is reasonable to transfuse non–red cell h t ti bl d d t b dhemostatic blood products based on clinical evidence of bleeding and gpreferably guided by point-of-care tests that assess hemostatic function in a timelythat assess hemostatic function in a timely and accurate manner. – Class IIa, Level C

Nuttall et al: JCTVA 1997;11:815-823

Transfusion Algorithms: gThe Response to Bleeding

POC Platelet Function Testing

TEG PlateletWorks Multiplate VerifyNow

U th Ri ht I t t!Use the Right Instrument!

Microvascular BleedingMicrovascular BleedingCoag tests and TEG

Plt ct <102K PT >16.6 Fib <144mg/dl

Coag es s a d G

Plt ct 102KMA <48mm

PT 16.6aPTT >57 Cryo

Fib 144mg/dl

Plt Tx or Rx FFPy

Nuttall et al: JCTVA 1997;11:815-823

Percent Transfused in OR

100

80

nts

ControlAlgorithm

40

60

% P

atie

P< 0.0001

20

%

0Plts+FFP Plts only FFP only None

Nuttall: Anesthesiology 2001;94:773-81

G G id d Al i hTEG Guided Algorithm

Plt Ct cTEG Fibw/wout hepnase

R>2X hTEG R Plt Ct<100KMA<45mm

hTEG R>20mm LY30>7.5% Fib<100mg/dl

Protamine Plts FFP EACA Cryo532 41

Shore-Lesserson et al: Anesth Analg 1999;88:312

St d d Al ith P lStandard Algorithm P valuePts tx’ed 17/52 7/53 <0 02Pts tx ednon-rbc

17/52 7/53 <0.02

Pts tx’ed 34/52 22/53 0 01Pts tx ed 34/52 22/53 0.01Platelets (U) 6.2±13 1.3±4.6 0.01( ) 6.2±13 1.3±4.6 0.01CTD 4hr( l)

262±247 229±138 NS(ml)CTD 24 hr 659±429 577±412 0.09

Sh L t l A th A l 1999 88 312

(ml)

Shore-Lesserson et al: Anesth Analg 1999;88:312

Clopidogrel PatientsClopidogrel PatientsPlt Count

>100,000 50-100 <50,000

Nl PFA Abnl PFA Nl PFA Abnl PFA

Assess PT 6 U Plts 12 U Plts6U Plts

Assess PTFFP Assess PTChen L: J Thorac Cardiovasc Surg 2004;128:425-31

T f iTransfusionsProsp-Clop Control Retro-Clop Control

PLT 9.0±1.7* 1.2±0.5 # 12.5±2.1* 2.3±0.3

PRBC 4.3±0.6* 2.3±0.5 6.4±0.8*^ 2.3±0.1

FFP 1 0±0 6 0 5±0 3 # 2 9±1 0* 1 0±0 1FFP 1.0±0.6 0.5±0.3 # 2.9±1.0* 1.0±0.1

Chen L: J Thorac Cardiovasc Surg 2004;128:425-31

Plasma + t-PA Whole Blood (aprotinin)

Tanaka et al: Anesth Analg 2008;106:732-738

Class I Recommendation

• A multi-disciplinary approach involving multiple stakeholders, institutional support, enforceable transfusion algorithms gsupplemented with point-of-care testing, and all of the already mentioned efficaciousand all of the already mentioned efficacious blood conservation interventions limits bl d t f i d id ti lblood transfusion and provides optimal blood conservation for cardiac operations. (Level of Evidence A)

In Conclusion• Cost effective hemostasis care involves a

bi i f i d di i licombination of strategies and disciplines• The tenets of patient blood managementThe tenets of patient blood management

include prevention of anemia, blood conservation, and optimal treatment of anemia with a multidisciplinary approachanemia with a multidisciplinary approach