SYNERGY

LMWHLMWH

ESSENCEESSENCE

19941994 19951995 19961996 19971997 19981998 19991999 20002000 20022002 20032003 20042004 20052005 2006200620012001

CURECURE

ClopidogrelClopidogrel

Bleeding riskBleeding risk

Ischemic riskIschemic risk

GP IIb/IIIa GP IIb/IIIa blockersblockers

PRISM-PLUSPRISM-PLUS

PURSUITPURSUIT

ACUITYTACTICS TIMI-18TACTICS TIMI-18

Early invasiveEarly invasive

PCIPCI ~ 5% stents~ 5% stents ~85% stents~85% stents Drug-eluting stentsDrug-eluting stents

ISAR-REACT 2

Milestones in ACS Management

OASIS-5

[ Fondaparinux ][ Fondaparinux ]

Anti-Thrombin RxAnti-Thrombin Rx

Anti-Platelet RxAnti-Platelet Rx

Treatment StrategyTreatment Strategy

HeparinHeparin

AspirinAspirin

ConservativeConservative

ICTUS

BivalirudinBivalirudin

REPLACE 2REPLACE 2

Ischemic Complications Ischemic

Complications

► Death

► MI

► Urgent TVR

► Death

► MI

► Urgent TVR

Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies

Composite Adverse Event EndpointsComposite Adverse Event Endpoints

Ischemic Complications Ischemic

Complications Hemorrhage HIT

Hemorrhage HIT

► Death

► MI

► Urgent TVR

► Death

► MI

► Urgent TVR

► Major Bleeding

► Minor Bleeding

► Thrombocytopenia

► Major Bleeding

► Minor Bleeding

► Thrombocytopenia

Composite Adverse Event EndpointsComposite Adverse Event Endpoints

Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies

Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies

Risk of events

Risk of bleeding

ThrombosisHemostasis

Two sides of the same coin

Degree of Anticoagulation

Ris

k

Balancing Events and BleedingBalancing Events and BleedingBalancing Events and BleedingBalancing Events and Bleeding

DeathDeath 4.3%4.3%

(Re)-Infarction(Re)-Infarction 2.5%2.5%

CHFCHF 8.0%8.0%

Cardiogenic ShockCardiogenic Shock 2.6%2.6%

StrokeStroke 0.8%0.8%

Non-CABG TransfusionNon-CABG Transfusion 9.9%9.9%

Bhatt DL, et al. Bhatt DL, et al. JAMAJAMA. 2004 Nov 3;292(17):2096-104. . 2004 Nov 3;292(17):2096-104.

CRUSADE In-Hospital OutcomesCRUSADE In-Hospital Outcomes

Quali sono i pazienti a rischio di

sanguinamento?

Quali sono i pazienti a rischio di

sanguinamento?

Bleeding in ACS

Domanda:Domanda:

Independent Independent Predictors of Predictors of Major Bleeding Major Bleeding in in Acute Coronary Acute Coronary SyndromesSyndromes

Moscucci, GRACE Registry, Moscucci, GRACE Registry, Eur Heart JEur Heart J. 2003 Oct;24(20):1815-23. . 2003 Oct;24(20):1815-23.

Predictors of Major Bleeding in ACSPredictors of Major Bleeding in ACS

► Older AgeOlder Age

► Female GenderFemale Gender

► Renal FailureRenal Failure

► History of BleedingHistory of Bleeding

► Right Heart CatheterizationRight Heart Catheterization

► GPIIb-IIIa antagonistsGPIIb-IIIa antagonists

P-valueP-valueRR (95% CI)RR (95% CI)Risk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CI

Predictors of Major BleedingPredictors of Major Bleeding

Age Age >>75 (vs. 55-75)75 (vs. 55-75)

AnemiaAnemia

CrCl <60mL/minCrCl <60mL/min

DiabetesDiabetes

Female genderFemale gender

High-risk (ST / biomarkers)High-risk (ST / biomarkers)

HypertensionHypertension

Heparin(s) + GPI (vs. Bivalirudin)Heparin(s) + GPI (vs. Bivalirudin)

1.56 (1.19-2.04)1.56 (1.19-2.04) 0.00090.0009

1.89 (1.48-2.41)1.89 (1.48-2.41) <0.0001<0.0001

1.68 (1.29-2.18)1.68 (1.29-2.18) <0.0001<0.0001

1.30 (1.03-1.63)1.30 (1.03-1.63) 0.02480.0248

2.08 (1.68-2.57)2.08 (1.68-2.57) <0.0001<0.0001

1.42 (1.06-1.90)1.42 (1.06-1.90) 0.01780.0178

1.33 (1.03-1.70)1.33 (1.03-1.70) 0.02870.0287

2.08 (1.56-2.76)2.08 (1.56-2.76) <0.0001<0.0001

Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

Results: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI Population

MA…MA…

REPLACE-2REPLACE-2Multivariate Predictors of Major BleedingMultivariate Predictors of Major Bleeding

RISK FACTORSRISK FACTORS Odds RatioOdds Ratio 95% CI95% CI p-valuep-value

Baseline risk factorsBaseline risk factors

Age Age >> 75 75 1.4821.482 1.009 to 2.1761.009 to 2.176 0.0450.045

Gender (M vs. F)Gender (M vs. F) 0.6520.652 0.477 to 0.8900.477 to 0.890 0.00720.0072

Prior AnginaPrior Angina 1.5891.589 1.077 to 2.3451.077 to 2.345 0.01970.0197

Creatinine clearance* Creatinine clearance* 0.9930.993 0.987 to 0.9980.987 to 0.998 0.00610.0061

AnemiaAnemia 1.4031.403 1.015 to 1.9391.015 to 1.939 0.04010.0401

Peri-procedural risk factorsPeri-procedural risk factors

Treatment Group (BIV vs. H+GPI)Treatment Group (BIV vs. H+GPI) 0.5080.508 0.352 to 0.7330.352 to 0.733 0.00030.0003

Provisional GPI receivedProvisional GPI received 2.6792.679 1.591 to 4.5121.591 to 4.512 0.00020.0002

Procedure Duration >1hProcedure Duration >1h 2.0492.049 1.217 to 3.4491.217 to 3.449 0.00690.0069

Time to Sheath Removal >6hTime to Sheath Removal >6h 1.6141.614 1.064 to 2.4481.064 to 2.448 0.02440.0244

ICU stay (days)†ICU stay (days)† 1.251.25 1.183 to 1.3211.183 to 1.321 <0.0001<0.0001

IABPIABP 8.7058.705 3.433 to 22.0723.433 to 22.072 <0.0001<0.0001Feit F et al.

Il sanguinamento influenza la prognosi

del paziente?

Il sanguinamento influenza la prognosi

del paziente?

Bleeding in ACS

Domanda:Domanda:

Moscucci M et al. Moscucci M et al. Eur Heart JEur Heart J 2003;24:1815-23. 2003;24:1815-23.

P<0.001

Overall Unstable NSTEMI STEMIOverall Unstable NSTEMI STEMI ACS AnginaACS Angina

Pat

ien

ts (

%)

Pat

ien

ts (

%)

Major Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACS

24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death

log rank p-value for all four categories <0.0001log-rank p-value for no bleeding vs. mild bleeding = 0.02log-rank p-value for mild vs. moderate bleeding <0.0001log-rank p-value for moderate vs. severe <0.001

Bleeding & OutcomesBleeding & Outcomes

Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12

Kaplan Meier Curves for 30-Day Death, Stratified by Bleed SeverityKaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity

N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT

Major Bleeding, Ischemic Endpoints, Major Bleeding, Ischemic Endpoints, and Mortalityand Mortality

P<0.0001 for all

Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)

Major and Minor Bleeding in PCIMajor and Minor Bleeding in PCIBleeding Increases Mortality and EventsBleeding Increases Mortality and Events

Kinnaird TD et al. AM J Cardiol 2003;92:930-5.

10,974 patients undergoing PCI, Washington Hospital Center, 1991-2000.

In-Hospital Clinical EventsIn-Hospital Clinical Events

MajorMajor(n=588)(n=588)

MinorMinor(n=1,394)(n=1,394)

NoneNone(n=8,992)(n=8,992)

DeathDeath 7.5%*7.5%*†† 1.8%*1.8%* 0.6%0.6%

Q-wave myocardial infarctionQ-wave myocardial infarction 1.2%*1.2%* 0.7%0.7%‡‡ 0.2%0.2%

Non-Q-wave myocardial infarctionNon-Q-wave myocardial infarction 30.7%*30.7%*†† 16.8%*16.8%* 11.8%11.8%

Repeat lesion angioplastyRepeat lesion angioplasty 1.9%*1.9%*§§ 0.8%0.8%‡‡ 0.3%0.3%

Major adverse cardiac eventMajor adverse cardiac event 6.6%*6.6%*†† 2.2%*2.2%* 0.6%0.6%

Bleeding ComplicationBleeding Complication

* p<0.001 versus none † p<0.001 versus minor ‡ p<0.01 versus none § p<0.05 versus minor

Come valutare l’entità del

sanguinamento?

Come valutare l’entità del

sanguinamento?

Bleeding in ACS

Domanda:Domanda:

Bleeding Incidence in ACS Clinical TrialsBleeding Incidence in ACS Clinical Trials

Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26 Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26

Bleeding DefinitionsBleeding Definitions

► TIMI DefinitionTIMI Definition MajorMajor

• ICHICH• Associated with Hgb decrease ≥ 5 g/dl or Associated with Hgb decrease ≥ 5 g/dl or

HCT decrease ≥ 15%HCT decrease ≥ 15% MinorMinor

• Observed blood loss associated with Hgb Observed blood loss associated with Hgb decrease ≥ 3 g/dl or HCT decrease ≥ 10%decrease ≥ 3 g/dl or HCT decrease ≥ 10%

• No identifiable source but Hgb decrease No identifiable source but Hgb decrease ≥ 4 g/dl or HCT decrease ≥ 12%≥ 4 g/dl or HCT decrease ≥ 12%

MinimalMinimal• Overt hemorrhage with Hgb drop < 3 g/dl or Overt hemorrhage with Hgb drop < 3 g/dl or

HCT drop < 9%HCT drop < 9%

Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54. Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54.

N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516 N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516

Bleeding DefinitionsBleeding Definitions

► GUSTO DefinitionGUSTO Definition Severe or life threateningSevere or life threatening

• ICH or hemodynamic compromise ICH or hemodynamic compromise requiring treatmentrequiring treatment

ModerateModerate• Requiring transfusionRequiring transfusion

MildMild• Not meeting criteria for Severe or Not meeting criteria for Severe or

ModerateModerate

Bleeding Scales Among Bleeding Scales Among NSTE ACS PatientsNSTE ACS Patients

Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26 Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26

TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858

► La trasfusione ha un impatto sulla

prognosi?

► La trasfusione è in grado di correggere

l’effetto negativo del sanguinamento?

► La trasfusione ha un impatto sulla

prognosi?

► La trasfusione è in grado di correggere

l’effetto negativo del sanguinamento?

Bleeding in ACS

Domanda:Domanda:

30-Day Survival By Transfusion Group30-Day Survival By Transfusion Group

Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562

Transfusion in ACSTransfusion in ACS

N=24,111N=24,111N=24,111N=24,111

METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials

METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials

*Transfusion as a time-dependent covariate*Transfusion as a time-dependent covariate

PRBC Transfusion Among NSTE ACS Patients:PRBC Transfusion Among NSTE ACS Patients:Cox Model for 30-day DeathCox Model for 30-day Death

Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562

N=24,111N=24,111N=24,111N=24,111METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials

METANALYSIS OF the GUSTOIIb,PURSUIT,and PARAGON b trials

Adjusted Risk of In-Hospital Outcomes Adjusted Risk of In-Hospital Outcomes

By Transfusion Status*By Transfusion Status*

*Non-CABG patients onlyYang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.Yang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.

N=74,271 ACS patients from CRUSADEN=74,271 ACS patients from CRUSADE

Increased 1-year mortality in transfused patientsIncreased 1-year mortality in transfused patientsAdjusted Odds Ratio 4.26 (2.25–8.08)Adjusted Odds Ratio 4.26 (2.25–8.08)

Transfusion Post PCI:Transfusion Post PCI:REPLACE 2 One Year MortalityREPLACE 2 One Year Mortality

P<0.0001

Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA, Feit F, Lincoff AM. CRT 2005. Abstract.

“storage lesions”:

aumento fragilità di membrana (ridotta deformabilità)

alterata capacità di trasporto dell’ossigeno

pH ridotto

riduzione del n° cellule vitali/unità

aumento delle citochine pro-infiammatorie (leucociti contaminanti)

alterata biologia dell’NO nel sangue conservato

bassi livelli di 2,3 difosfoglicerati -> aumentata affinità dell’O2

per l’Hb

EMOTRASFUSIONI NEGLI ANZIANI CON IMA

Wu W-C NEJM 2001;345:1230

78.974 pz Medicare con IMA > 65 aa

ematocrito (%)

OR (95% CI) di morte < 30 gg con aggiustamento per i fattori clinici, i farmaci e i predittori di trasfusioni

5.0 – 24.0 0.22 (0.11 - 0.45)

24.1 – 27.0 0.48 (0.34 – 0.69)

27.1 – 30.0 0.60 (0.47 – 0.76)

30.1 – 33.0 0.69 (0.53 – 0.89)

33.1 – 36.0 1.13 (0.89 – 1.44)

36.1 – 39.0 1.38 (1.05 – 1.80)

39.1 – 38.0 1.46 (1.18 – 1.81)

High Risk Patient Subgroups

Bleeding Risks—Transfusions by AgeBleeding Risks—Transfusions by Age

Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16. Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16.

6,002 patients in REPLACE-26,002 patients in REPLACE-2806 patients (13.4%) classified as elderly, >75 years of age806 patients (13.4%) classified as elderly, >75 years of age

p<0.0001 p=0.0001

REPLACE-2:REPLACE-2:Elderly Patients Have Increased Major Bleeding and Elderly Patients Have Increased Major Bleeding and

TransfusionsTransfusions

= Not Elderly, <75

= Elderly, >75

Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.

p<0.0001 p=0.0001

6,002 patients in REPLACE-2.6,002 patients in REPLACE-2. 806 patients (13.4%) classified as elderly, >75 years of age.806 patients (13.4%) classified as elderly, >75 years of age.

Elderly Patients in REPLACE-2:Elderly Patients in REPLACE-2:Increased 30-Day Mortality With Major Bleeding and TransfusionsIncreased 30-Day Mortality With Major Bleeding and Transfusions

Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.

Excessive Dosing ofExcessive Dosing ofAnticoagulants by AgeAnticoagulants by Age

Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16. Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16.

12.5

28.7

8.5

33.137

12.5

64.5

38.5

16.5

0

10

20

30

40

50

60

70

LMW Heparin UF Heparin GP Iib/IIIa

% E

xcse

ssiv

e d

ose

<65 yrs 65-75 yrs >75 yrs

Excess Dosing of Gp IIb/IIIa Excess Dosing of Gp IIb/IIIa and Bleeding in Womenand Bleeding in Women

OverallOverallOverallOverall

WomenWomenWomenWomen

MenMenMenMen

1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)

1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)

1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)

0.50.50.50.5 1.01.01.01.0 1.51.51.51.5 2.02.02.02.0 2.52.52.52.5

Excess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to Bleed

Alexander KP, et. al. Circulation 2006Alexander KP, et. al. Circulation 2006

N=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADE

Bleeding is Increased in Patients With Bleeding is Increased in Patients With Impaired Renal Function Undergoing PCIImpaired Renal Function Undergoing PCI

≥≥ 60 ml/min60 ml/min N=4824 N=4824

< 60 ml/min< 60 ml/min N=886 N=886 p valuep value

30-d Death30-d Death 5 (0.1%)5 (0.1%) 14 (1.6%)14 (1.6%) < 0.001< 0.001

30-d Myocardial infarction30-d Myocardial infarction 305 (6.3%)305 (6.3%) 75 (8.5%)75 (8.5%) 0.0180.018

30-d urgent revascularization30-d urgent revascularization 61 (1.3%)61 (1.3%) 10 (1.1%)10 (1.1%) 0.7380.738

Triple ischemic endpointTriple ischemic endpoint 338 (7.0%)338 (7.0%) 84 (9.5%)84 (9.5%) 0.0100.010

In-hospital protocol major In-hospital protocol major bleedingbleeding 123 (2.5%)123 (2.5%) 54 (6.1%)54 (6.1%) < 0.001< 0.001

TIMI major + minor bleedingTIMI major + minor bleeding 114 (2.4%)114 (2.4%) 46 (5.2%)46 (5.2%) < 0.001< 0.001

Creatinine ClearanceCreatinine Clearance

Chew DP et al. Am J Cardiol 2005;95:581–585.

enoxaparin CrCl < 30 controindicata o dose

fondaparinux CrCl < 30controindicata – tuttavia emorragie vs enox

bivalirudinCrCl < 30emodialisi

dose 1 mg/kg/h dose 0.25 mg/kg/h

tirofiban CrCl < 30 dose 50 %

eptifibatideCrCl < 50 < 30

dose 50 % controindicato

abciximabvalutazione attenta del rischio emorragico

farmaci antitrombotici e antiaggreganti, insufficienza renale e

rischio emorragico

Major Bleeding is IncreasedMajor Bleeding is Increasedin Anemic Patients Undergoing PCIin Anemic Patients Undergoing PCI

6,010 patients in REPLACE-2.1,362 patients (22.7%) classified as anemic based upon WHO definition.

Major bleeding = 3.2%

Major Bleeding

2.8%

4.9%

P=0.0001

Protocol definition: >3g/dL drop in HgB,

intracranial, retroperitoneal,

2U transfusion

Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl A]:1037-13-31A. Abstract.A]:1037-13-31A. Abstract.

NSTE-ACS MortalityNSTE-ACS MortalityStratified by HemoglobinStratified by Hemoglobin

Sabatine MS. Circulation 2005

UnadjustedUnadjusted

Hb (g/dL)Hb (g/dL) nn OROR (95% Cl)(95% Cl) OROR (95% Cl)(95% Cl) P P valuevalue

>17>17 216 216 1.471.47 (1.03–2.10)(1.03–2.10) 1.451.45 (0.94–2.23)(0.94–2.23) 0.0930.093

16–1716–17 812 812 1.211.21 (0.97–1.51)(0.97–1.51) 1.271.27 (0.98–1.65)(0.98–1.65) 0.0660.066

15–1615–16 21302130 1.0 1.0 referencereference 1.0 1.0 referencereference

14–1514–15 33903390 1.061.06 (0.89–1.22)(0.89–1.22) 1.111.11 (0.93–1.33)(0.93–1.33) 0.2510.251

13–1413–14 35203520 1.021.02 (0.88–1.19)(0.88–1.19) 1.041.04 (0.86–1.24)(0.86–1.24) 0.7090.709

12–1312–13 23312331 1.091.09 (0.92–1.28)(0.92–1.28) 1.071.07 (0.88–1.30)(0.88–1.30) 0.5140.514

11–1211–12 976 976 1.201.20 (0.97–1.47)(0.97–1.47) 1.041.04 (0.81–1.34)(0.81–1.34) 0.7550.755

10–1110–11 343 343 1.411.41 (1.05–1.89)(1.05–1.89) 1.291.29 (0.92–1.82)(0.92–1.82) 0.1450.145

9–109–10 342 342 2.442.44 (1.88–3.18)(1.88–3.18) 2.692.69 (2.01–3.60)(2.01–3.60) <0.001<0.001

8–98–9 306 306 2.242.24 (1.69–2.96)(1.69–2.96) 2.452.45 (1.80–3.33)(1.80–3.33) <0.001<0.001

<8<8 137 137 3.973.97 (2.76–5.70)(2.76–5.70) 3.493.49 (2.35–5.20)(2.35–5.20) <0.001<0.001

Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.

Unadjusted and adjusted odds ratios for cardiovascular mortality in patientsUnadjusted and adjusted odds ratios for cardiovascular mortality in patientswith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobinwith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobin

Adjusted for baseline characteristicsAdjusted for baseline characteristics

indicazioni alla trasfusione di piastrine

Shander A Pharmacotherapy 2007;27(9 Pt 2):57S

piastrinopenia severa (< 50 x 103/mmc) in caso di sanguinamento attivo

prevenzione del sanguinamento in caso di piastrinopenia molto severa

(< 5-10 x 103/mmc)

piastrinopenia severa (< 50 x 103/mmc) prima di una procedura invasiva

prevenzione del sanguinamento spontaneo in pazienti con piastrinopenia

severa (<10-50 x 103/mmc), in caso di sepsi, uso di antibiotici, altre anoma-

lie della coagulazione

nei disordini della funzione piastrinica (uremia, tromboastenia, farmaci

antipiastrinici), in caso di sanguinamento attivo.

E’ causata da anticorpi diretti contro il complesso PF4 piastrinico ed eparina

Compare dopo circa 5-10 giorni dall’ inizio della terapia in pazienti non precedentemente esposti (oltre 100 gg), in poche ore se vi è stato un recente trattamento

Può essere molto severa anche valori inferiori a 10.000 per mmc, con lenta risalita (4-14 gg), dopo la sospensione del farmaco.

E’ raramente associata a fenomeni emorragici, invece predominano le complicanze trombotiche (25-50% dei pz) con un rischio di trombosi 30 volte maggiore che nella popolazione di controllo

E’ 10 volte più frequente nei pz trattati con UHF vs LMWH

Se sospetto clinico ricerca di anticorpi per il complesso PF4-eparina, eventuale test funzionali di aggregazione piastrinica

-> sospensione della terapia eparinica

-> anticoagulazione

1. Associazione temporale

2. Nova insorgenza di trombosi

3. Risalita dopo sospensione

dosaggio ASA (+ clopidogrel) ed emorragie - CURE -

Peters RJG Circulation 2003;108:1682.