Prof. Rosanna Abbate Università di Firenze AOU Careggi

Preoperative hemostatic evaluation Routine screening Surgical Risk Approach Low Moderate or high History only (?) History, PTT, PT, Plt count Consultation History Approach Negative or minimal for bleeding Suggestive of bleeding disorder PT, PTT, Plt count, biochemical profile, complete blood count and differential,review of peripheral blood smear Add to above as indicated: BT,, von Willebrand atg F VIII,F IX,F XI, F XIII Francis and Kaplan Clin Med Cardio, Fi

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 piastrinica T.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 emorragica intervento 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 Normal PTb 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 * Fibrinogen (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 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 Peterson, Arch Surg 1998 Clin Med Cardio, Fi

VARIABILITY OF BLEEDING TIME intra observer 80 70 60 50 40 30 20 10 n=66 CV %, MEAN + SD 80 inter observer 70 60 50 40 30 20 10 n=10 Clin Med Gen Card, Fi De Caterina, Blood 1994

Proportion of pts with complication 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 test .07 .06 .05 BT discontinued .04 Proportion of pts with complication .03 .02 .01 0.00 Apr98 Feb98 Mar98 May98 Jun98 Jul98 Aug98 Sept98 Oct98 Nov 98 Dec98 Jan99 Feb99 Mar 99 Apr 99 May 99 June 99 Lehman,Clin Chem 2001 Clin Med Cardio, Fi

Clinical practice behavior before and after discontinuation BT test available 2/98-6/98 BT test available 9/98-1/99 BT test unavailable 2/99-6/99 p Monthly plt unit transf Total plt-aggr studies Total pts receiving DDAVP Uremic pts receiving DDAVP 44.814.8 17 NA 42.013.9 9 24 22 41.68.9 9 10 8 0.687 0.958 NT NA not assessed NT not tested Lehman,Clin Chem 2001 Lehman,Clin Chem 2001 Clin Med Cardio, Fi Clin Med Cardio, Fi

Algorithm for evaluating the risk of bleeding after discontinuation of BT Patient and/or family history of bleeding Lehman,Clin Chem 2001 No Yes No test Necessary Pt, PTT, Plt count Normal Abnormal von Willebrand’s work-up Consult Hematology Normal Abnormal Plt Aggr studies Consult Hematology Clin Med Cardio, Fi

Peripheral Vascular Reconstructive Surgery 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 preoperatively (grade 1A). The addition of dipyridamole (75 mg three times daily) to aspirin may provide additional benefit (grade 2B) Jackson MR et al, CHEST 2001

Test for heterogenecy: 2 = 4.0: n.s. INDIRECT COMPARISONS OF PROPORTIONAL EFFECTS OF ANTIPLATELET THERAPY STARTED BEFORE OR AFTER VASCULAR PROCEDURES ON OCCLUSION Time antiplatelet therapy began N° of triale with data OCCLUSION STRATIFIED STATISTICS Odds ratio and confidence interval (Antiplatelet: Control) % Odds reduction (SD) Anti-platelet Adjusted controls O-E Variance 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† 0 0.5 1.0 1.5 2.0 Test for heterogenecy: 2 = 4.0: n.s. Antiplatelet therapy better Antiplatelet therapy worse Treatment effect 2P<0.00001

Multivariate regression analysis* PAD pts n=280; ctrl n=280 2.9 (1.6-5.1) p < 0.0001 Hcy 3.1 (1.8-5.2) p < 0.0001 Lp (a) 3.4 (1.8-6.1) p < 0.001 PAI-1 3.4 (1.8-6.1) p = 0.03 Prothrombin variant 8.6 (1.4-51.3) p = 0.02 ACA+ *Adjusted for all traditional risk factors 1 2 3 4 5 6 7 8 9 10 OR (95% CI) Sofi et al J Vasc Surg 2005

Association of risk factors at multivariate analysis* 2.9 (1.6-5.1) Hcy PAD pts n=280;ctrl n=280 3.1 (1.8-5.2) Lp (a) p < 0.0001 37.7 (3.7-381.5) Hcy x Lp(a) 7.4 (4.2-12.9) Dyslipidemia 29 (6.2-51.3) Lp(a) x dyslipidemia p = 0.02 *Adjusted for all traditional risk factors 1 2 3 4 5 6 7 8 9 10 OR (95% CI) Sofi et al J Vasc Surg 2005

ACA and occluded bypass grafts Anticardiolipin positive patients 100 Anticardiolipin negative patients 80 % cumulative patency 60 40 20 12 24 36 48 60 72 84 Clin Med Card FI Months Taylor et al. Ann Surg 1994

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 inexpensive tests (platelet count, aPTT, and possibly PT), knowing that their main usefulness is to provide baseline values for patients who will undergo a strong hemostatic 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* 15 420 Normal 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 a angle (degrees) NS NS MA (mm) NS NS MA +30 (mm) NS NS *P< 0.05 Nuttall et al, J Cardiothor Vasc Anesth, 1997

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 Postoperative Hematoma No Postoperative Hematoma Factor XIII >60% <60% 3 8 23 Gerlach,Surg Neurol 2000 Clin Med Cardio, Fi

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) Gerlach,Surg Neurol 2000 Clin Med Cardio, Fi

IL LABORATORIO DI EMOSTASI NELLA VALUTAZIONE DEL RISCHIO EMORRAGICO Valutazione preoperatoria Valutazione intra e postoperatoria

Risk of bleeding with surgical procedures Type of surgery Examples Low Moderate High Nonvital organs involved, exposed surgical site,limited dissection Vital organs involved deep or extensive Bleeding likely to compromise surgical results, bleeding complications frequent Lymph node biopsy, Dental extraction Laparotomy, thoracotomy mastectomy Neurosurgery, Ophthalmic surgery,CP bypass, Prostatic surgery Surgery to stop bleeding Francis and Kaplan Clin Med Cardio, Fi

Chronic Extremity Arterial Insufficiency Sixth ACCP Consensus Confeterence on Antithrombotic Therapy Chronic Extremity Arterial Insufficiency 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+). Clin Med Card –FI Jackson MR et al, CHEST 2001

Sixth ACCP Consensus Confeterence on Antithrombotic Therapy Chronic Extremity Arterial Insufficiency 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. Clin Med Card –FI Jackson MR et al, CHEST 2001

Chronic Extremity Arterial Insufficiency Sixth ACCP Consensus Confeterence on Antithrombotic Therapy Chronic Extremity Arterial Insufficiency 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). Clin Med Card –FI Jackson MR et al, CHEST 2001

Chronic Extremity Arterial Insufficiency Sixth ACCP Consensus Confeterence on Antithrombotic Therapy Chronic Extremity Arterial Insufficiency We recommend that pentoxifylline should not be routinely used in patients with intermittent claudication (grade 1B). Clin Med Card –FI Jackson MR et al, CHEST 2001