Prof. Rosanna Abbate Università di Firenze AOU Careggi.

Prof. Rosanna Abbate

Università di Firenze

AOU Careggi

Preoperative hemostatic evaluation

Low

Moderate or high

History only (?)

History, PTT, PT, Plt count

Surgical Risk

Routine screeningApproach

Francis and Kaplan Clin Med Cardio, Fi

History

Consultation

Approach

Negative or minimalfor bleeding

Suggestive ofbleeding disorder

PT, PTT, Plt count, biochemicalprofile, complete blood count anddifferential,review of peripheral blood smear

Add to above as indicated:BT,, von Willebrand atg F VIII,F IX,F XI, F XIII

IL LABORATORIO DI EMOSTASI NELLA VALUTAZIONE DEL RISCHIO EMORRAGICO OPERATORIO (da Rappaport)

LIVELLO 1 (rischio minimo)Anamnesi negativa - Intervento minore NESSUN TEST

LIVELLO 2 (rischio basso)Anamnesi negativa - Intervento maggiore aPTT

Conta piastrinicaT.sanguinamento (?)

LIVELLO 3 (rischio moderato)Anamnesi sospetta o intervento di particolare impegno (cardiochirurgia, SNC, prostata) idem +

PT XIII (?)

LIVELLO 4 (rischio elevato)Anamnesi sicura per patologia emorragicaintervento minore o maggiore idem + VIII, IX, XI, TT, ev.ricerca inibitori etc.

In caso di esami alterati si procede con ulteriori indagini fino a chiarirne il quadro

ANAMNESI EMOSTASIOLOGICA ESSENZIALE PREOPERATORIA

A) facilità alle ecchimosi compaiono frequentemente? senza cause apparenti? più grandi di una moneta di 100 lire?B) emorragie pregresse: ha eseguito tonsillectomia, biopsie o altre operazioni? se sì, ha avuto particolari emorragie? ha avuto parti? se sì. vi sono state complicanze emorragiche? ha avuto emorragie durate per più di un giorno dopo estrazione dentaria o piccola chirurgica? C) patologie acquisite ha sofferto di malattie epatiche o renali? quali malattie ha avuto negli ultimi anni?D) farmaci nell’ultima settimana ha assunto aspirina, ticlopidina, altri antinevralgici o antidolorifici?E) storia familiare ha avuto consanguinei con problemi emorragici spontanei o post-operatori?

Sensitivity of PT and aPTT to procoagulants

Approximate level For NormalPTb aPTTb

Procoagulant

Fibrinogen (Factor I) 100 mg/dL 60

mg/dL

Prothrombin (Factor II) 50%

15%

Factor V 50% 40%

Factor VII 50%

Factor VIII 35%

Factor IX 20%

Factor X 60% 25%

Factor XI 30%

Factor XII 20%•Data from the Hematology Science, Clinical Pathology Department, Warren G, Magnusson Clinical Center, derived using the STA (Diagnostica Stago, Asnieres, France) and provided by Ms. Khanh Nghiem and Dr. Margaret Rick.

Clin Med Card (Fi)

Sensitivity of PT and aPTT to procoagulants

Hemostasis *ProcoagulantFibrinogen (Factor I) 50-100 mg/dL

Prothrombin (Factor II) 20-30%

Factor V >20%

Factor VII >10%

Factor VIII >40%

Factor IX >30%

Factor X >20%

Factor XI >50% (variable)

Factor XII 0

•Data from Roberts HR, Bingham MD: Other coagulation factor deficiencies. In Loscalzo J, Schafer AL (eds): Thrombosis and Hemorrhage, Baltimore, Williams & Wilkins, 1998, pp.773-802.

Clin Med Card Fi

Preoperative bleeding time

In the absence of a clinical history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedure

Peterson, Arch Surg 1998 Clin Med Cardio, Fi

A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedure

The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or non steroidal anti-inflammatory agents, or who have a platelet defect attributable to these drugs

80706050

40

20100

30

n=66

8070605040

3020100

n=10

CV

%, M

EA

N +

SD

VARIABILITYOF BLEEDING TIME

Clin Med Gen Card, Fi De Caterina, Blood 1994

intra observer

inter observer

Lehman,Clin Chem 2001Clin Med Cardio, Fi

0.00

.01

.02

.03

.04

.05

.06

.07

Feb98

Mar9

8Apr98

May9

8Ju

n98

Jul9

8

Oct9

8

Mar 9

9

Aug98

Sept9

8

Dec9

8Ja

n99

Feb99

Apr 9

9M

ay 99

June 9

9

Nov 9

8

BT discontinued

Rate of postprocedural hemorrhage or hematoma for patients in the major Surgery Risk Pool for the 12 months before and 5

months after discontinuation of the BT testP

rop

ort

ion

of

pts

wit

h c

om

plicati

on



Clinical practice behavior before and after discontinuation

Monthly plt unit transf

Total plt-aggr studies

Total pts receiving DDAVP

Uremic pts receiving DDAVP

44.814.8

17

NA

NA

42.013.9

9

24

22

0.687

0.958

NT

NT

NT

BT test available2/98-6/98

p

41.68.9

9

10

8

BT test available9/98-1/99

BT test unavailable2/99-6/99

NA not assessedNT not tested

Lehman,Clin Chem 2001

Clin Med Cardio, Fi

Algorithm for evaluating the risk of bleeding after discontinuation of BT

Patient and/or familyhistory of bleeding

No

No testNecessary

Normal Abnormal

von Willebrand’swork-up Consult

Hematology

Normal Abnormal

Plt Aggrstudies

Consult Hematology

Yes

Pt, PTT,Plt count

Jackson MR et al, CHEST 2001

Sixth ACCP Consensus Conference on Antithrombotic Therapy

Peripheral Vascular Reconstructive Surgery

We recommend that clinicians use aspirin (81 to 325 mg/d)

in patients having prosthetic, femoropopliteal bypass

operations, and antiplatelet therapy should be begun

preoperativelypreoperatively (grade 1A). The addition of dipyridamole

(75 mg three times daily) to aspirin may provide additional

benefit (grade 2B)

INDIRECT COMPARISONS OF PROPORTIONAL EFFECTS OF ANTIPLATELET THERAPY STARTED BEFORE OR AFTER VASCULAR PROCEDURES ON

OCCLUSIONTime

antiplatelet

therapy began

N° of triale with

data

Odds ratio and confidence interval

(Antiplatelet: Control)

% Odds reduction

(SD)Anti-platelet

Adjusted controls

OCCLUSION

O-E Variance

STRATIFIED STATISTICS

Before procedure 25 569/2966 829/2949 -102.6 189.6 42.6% (6)

(19.2%) (28.1%) Up to 24h after 8 70/781 158/780 -31.6 36.8 58% (11)procedure (10.1%) (20.3%)

More than 24h 12 177/942 262/982 -35.2 75.0 37% (9) after procedure (18.8%) (26.7%)ALL PROCEDURE 45 825/4589 1249/4711 -169.5 301.4 43% (4) TRIALS†

Test for heterogenecy: 2 = 4.0: n.s.

0 0.5 1.0 1.5 2.0

Antiplatelet therapy better

Antiplatelet therapy worse

Treatment effect 2P<0.00001

1 2 3 4 5 6 7 8 9 10

Prothrombin variant

OR (95% CI)

2.9 (1.6-5.1)

0

Hcy p < 0.0001

p < 0.001PAI-1

3.1 (1.8-5.2)

Lp (a)

Multivariate regression Multivariate regression analysis*analysis*

p < 0.0001

3.4 (1.8-6.1)

ACA+

3.4 (1.8-6.1)

8.6 (1.4-51.3)

p = 0.03

p = 0.02

*Adjusted for all traditional risk factors Sofi et al J Vasc Surg 2005

PADPAD pts n=280; ctrl n=280

1 2 3 4 5 6 7 8 9 10

Hcy x Lp(a)

OR (95% CI)

2.9 (1.6-5.1)

0

Hcy

3.1 (1.8-5.2)Lp (a)

Association of risk factors at multivariate Association of risk factors at multivariate analysis*analysis*

37.7 (3.7-381.5)

29 (6.2-51.3)

p < 0.0001

p = 0.02

Dyslipidemia

7.4 (4.2-12.9)

Lp(a) x dyslipidemi

a

*Adjusted for all traditional risk factors Sofi et al J Vasc Surg 2005

PADPAD pts n=280;ctrl n=280

ACA and occluded bypass graftsACA and occluded bypass grafts%

cum

ula

tive p

ate

ncy

0

20

40

60

80

100

0 12 24 36 48 60 72 84 Months Taylor et al. Ann Surg 1994Clin Med Card FI

Anticardiolipin negative patients

Anticardiolipin positive patients

The cardiac surgical literature is remarkably devoid of carefully controlled, randomized trials that would

permit definitive conclusions concerning routine preoperative coagulation testing. At present, it

appears appropriate to perform a few inexpensivetests (platelet count, aPTT, and possibly PT),

knowing that their main usefulness is to providebaseline values for patients who will undergo a stronghemostatic challenge along with various degrees and

methods of anticoagulation, and who may require transfusions to restore normal haemostasis after CPB

Clin Med Gen Card, Fi Ph De Moerloose 1996

RELATIONSHIP BETWEEN HEMORRHAGE AND SCREENING TESTS IN 4499 PATIENTS

(data pooled from 3 studies)

Hemorrhage No Hemorrhage

Abnormal tests* 15 420Normal tests 70 3994

Prevalence of Bleeding = 85/4499 (2%)Sensitivity = 15/85 (18%)Specificity = 3994/4414 (90%)PPV = 15/435 (3%)NPV = 3994/4064 (98%)

* Test included prothrombin time, partial thromboplastin time, and platelet count

IL LABORATORIO DI EMOSTASI NELLA

VALUTAZIONE DEL RISCHIO EMORRAGICO

•Valutazione preoperatoria

•Valutazione intra e postoperatoria

VALUTAZIONE DELL’EMOSTASI NEL BLOCCO OPERATORIO

- Ematocrito- Piastrine- ACT- PT- APTT- TEG ?- Funzione piastrinica (PFA, Sonoclot)?

Clin Med Gen Card, Fi

COAGULATION TESTS PREDICT BLEEDING AFTER CARDIOPULMONARY BYPASS (10 min after CPB)

24 hr Chest Intraoperative Test Tube Bleeding Bleeding

Platelets (109/L) NS -0.32 MPV (fL) -0.31* NS Platelet crit -0.27* NS BT (Duke) (min) NS NS PT (sec) 0.24* 0.39* aPTT (sec) 0.27* 0.27* Fibrinogen (mg/dL) -0.33* NS

TEG Profile R (mm) NS NS R+ K (mm) NS NS angle (degrees) NS NS MA (mm) NS NS MA +30 (mm) NS NS

Nuttall et al, J Cardiothor Vasc Anesth, 1997

*P< 0.05

BLOOD PRODUCT USE, OPERATIVE TIMES, CHEST TUBE DRAINAGE, AND EXPLORATION

FOR POSTOPERATIVE (24H) BLEEDING (CBP) (1)

Algorithm Standard therapy group therapy group

(n=30) (n=36)

Platelet concentrates Intraop (U) 3.9+4.1 6.7+6.0 Postop (U) 1.6+5.9 6.4+8.2*

Frozen plasma Intraop (U) 0.4+1.1 2.4+2.8# Postop (U) 1.2+1.9 2.7+3.6 Red blood cells Intraop (U) 2.3+1.5 3.6+3.4 Postop (U) 1.9+1.7 4.1+4.1§

* p<0.05 # p<0.001 § p<0.01 Despotis et al, J Thor card Surg, 1993

BLOOD PRODUCT USE, OPERATIVE TIMES, CHEST TUBE DRAINAGE, AND EXPLORATION

FOR POSTOPERATIVE (24H) BLEEDING (CBP) (2)

Algorithm Standard therapy group therapy group

(n=30) (n=36)

DDAVP (%) 60% 44%

MVB time (min) 27+16 66+45#

Post-CPB time (min) 69+24 108+54#

Chest tube drainage (ml) Intraop + postop hour 1 158+169 326+258§ Postop hours 2-4 299+399 436+444 Postop hours 5-8 256+353 456+431 Postop hours 9.24 501+247 947+1180

Exploration (%) 3% 14%

* p<0.05 # p<0.001 § p<0.01 Despotis et al, J Thor card Surg, 1993

Association of Factor XIII deficiency and postoperative hematoma after

neurosurgical procedures

Gerlach,Surg Neurol 2000 Clin Med Cardio, Fi

Factor XIII>60%

Factor XIII<60%

3

8

PostoperativeHematoma

No PostoperativeHematoma

23

0

Conditions with low factor XIII concentrations

Major surgery

Sepsis

Disseminated intravascular coagulation

Hepatic diseases (hepatitis, acute hepatitis

failure)

Chronic inflammatory bowel diseases

Purpura Schönlein-Henoch

Hematologic disorders (leukemia,

myelodysplastic syndrome)

Clin Med Cardio, FiGerlach,Surg Neurol 2000

IL LABORATORIO DI EMOSTASI NELLA

VALUTAZIONE DEL RISCHIO EMORRAGICO

•Valutazione preoperatoria

•Valutazione intra e postoperatoria

Risk of bleeding with surgical procedures

Low

Moderate

High

Nonvital organsinvolved, exposed surgical site,limiteddissection

Vital organs involved deep or extensivedissection

Bleeding likely to compromise surgicalresults, bleeding complications frequent

Risk Type of surgery Examples

Lymph node biopsy,Dental extraction

Laparotomy, thoracotomymastectomy

Neurosurgery, Ophthalmicsurgery,CP bypass, Prostatic surgerySurgery to stop bleeding

Francis and Kaplan Clin Med Cardio, Fi

Clin Med Card –FI Jackson MR et al, CHEST 2001

Sixth ACCP Consensus Confeterence on Antithrombotic Therapy

Chronic Extremity Arterial Insufficiency

1. Aspirin alone or in combination with dipyridamole may

modify the natural history of intermittent claudication.

As these patients are at high risk of vascular events (stroke

and MI), we recommend life-long aspirin (81 to 325 mg/d) in

the absence of contraindications

(grade 1C+).



Chronic Extremity Arterial Insufficiency4. For patients experiencing disabling claudication, particularly

when lifestyle modification alone is ineffective and

revascularization cannot be offered or is declined by the

patient, we recommend a trial of cilostazol therapy (grade

2A). Cilostazol is not recommended for routine use in all

patients with intermittent claudication because of its high

cost and modest clinical benefit.



Chronic Extremity Arterial Insufficiency2. Clopidogrel may be superior to aspirin in reducing ischemic

ischemic complications in patients with peripheral vascular

disease and intermittent claudication, and we recommend

that clinicians consider clopidogrel for treatment

(grade 2A).



Chronic Extremity Arterial Insufficiency

3. We recommend that pentoxifylline should not be routinely

used in patients with intermittent claudication (grade 1B).

Prof. Rosanna Abbate Università di Firenze AOU Careggi.

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