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Modern Transfusion Management in Cardiovascular Surgery
Linda Shore-Lesserson, M.D.,Professor of AnesthesiologyAlbert Einstein School of MedicineMontefiore Medical CenterBronx, New York,
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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
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Patient Blood Management- CT SurgeryPreop Blood Conservation Treat Anemia
AnesthAnesthAnesth
SurgAnesth
SurgSurgMed/Card
ICUPerf
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Patient Blood Management CT SurgeryPreop Blood Conservation Treat Anemia
Patient Blood Management- CT Surgeryp
AnesthAnesth Anesth
SurgS
SurgSurg
Med/CardCard
ICUPerf
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Annals of Thoracic Surgery 2007;83:S27-86
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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
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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
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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
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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
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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
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Antifibrinolytic Agents MOAAntifibrinolytic Agents- MOAKallikrein Aprotinin
XIIIXL fibrin
Aprotinin
IIaXL fibrin
XIIIaPltPlt
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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
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Factor VIIa and Tube DrainageFactor VIIa and Tube Drainage
Karkouti: Transfusion 2005;45:26-34
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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
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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
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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
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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
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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
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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
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CPB-Platelet Effects
ThrombinThrombinThrombin receptor
ADPGpIIb/IIIaGpIIb/IIIaGpIIb/IIIa AggregationGpIIb/IIIaGpIIb/IIIa Aggregation
PlateletAdhesion
Epinephrine
Endothelium
vWF
Exposed Collagen
Endothelium
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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
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Off Pump Cardiac SurgeryOff Pump Cardiac SurgeryClass IIa, Level A,
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Cheng et al: Anesthsiology 2005;102:199-203
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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
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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
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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
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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
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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
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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
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Transfusion Algorithms: gThe Response to Bleeding
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POC Platelet Function Testing
TEG PlateletWorks Multiplate VerifyNow
U th Ri ht I t t!Use the Right Instrument!
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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
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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
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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
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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
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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
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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
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Plasma + t-PA Whole Blood (aprotinin)
Tanaka et al: Anesth Analg 2008;106:732-738
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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)
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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
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