Anticoagulanti e Rischio Emorragico e Trombotico
Anticoagulanti e Rischio Emorragico e Trombotico
Anticoagulanti e Rischio Emorragico e Trombotico
Anticoagulanti e
Rischio emorragico e
trombotico: il ruolo
dell’anestesista
1
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RISCHIO EMORRAGICO
RISCHIO TROMBOEMBOLICO
evidenze limitate
ClinicalTrials.gov, US National Institutes of Health.
PERIOP 2
250.000 pt/anno Chest 2012; 141: e326s- e350s
ClinicalTrials.gov, US National Institutes of Health.
The BRIDGE Study
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RISCHIO TROMBOEMBOLICO
Fattori di rischio correlati al paziente
RISCHIO TROMBOEMBOLICO
RISCHIO TROMBOEMBOLICO
PROFILASSI
Chirurgia
minore senza altri
fattori di rischio a
parte l’età
Basso rischio –
mobilizzazione
precoce
Chirurgia
maggiore + età <40
senza altri fattori di
rischio
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RISCHIO TROMBOEMBOLICO
PROFILASSI
Chirurgia
maggiore con età Chirurgia
>40 o altri fattori minore con fattori
rischio rischio addizionali
oltre l’età
Rischio Traumi maggiori
medio-alto:
profilassi con
LMWH + Chirurgia
oncologica
mobilizzazione addominale
precoce pelvica
Amputazioni
maggiori arti inf.
Chirurgia
Paralisi arti inf. addominale maggiore
in pazienti con VTE
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! Rischio moderato
1. Valvola aortica di nuova generazione con un solo fattore di rischio
! Rischio basso
1. Valvola aortica di nuova generazione senza FA o altri fattori di rischio
(*) Precedenti TE, FA, insuff. Vsx, stato ipercoagulabilità noto, diabete, età>
75aa, I.A., scompenso.
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Fibrillazione atriale
! Alto rischio: CHADS2 score 4 – 6
con o senza valvulopatia associata
! Rischio moderato: CHADS2 score 2 – 3
senza valvulopatia associata ≥2
! Basso rischio: CHADS2 score 0 – 1
senza valvulopatia associata
Tromboembolismo
! Alto rischio
1. VTE < 1-3 mesi
2. TE con trombofilia severa (deficit prot. C, prot. S, antitrombina; ab-
antifosfolipidi o anomalie multiple)
3. TE ricorrenti idiopatici
4. Neoplasia attiva < 6 mesi
5. Ictus o TIA o ATE < 3 mesi
! Rischio moderato
1. VTE < 3-6 mesi
2. Trombofilia non severa ( eterozigosi fatt. V Leiden, fatt. II)
3. Neoplasia non attiva
4. Stroke – TIA ricorrenti senza fattori di rischio per embolismo cardiaco
! Basso rischio
1. VTE > 6 mesi, senza fattori di rischio aggiuntivi
2. Malattie cerebro-vascolari senza ricorrenti stroke/TIA
Tromboprofilassi: Efficacia
70
64.3
Total knee replacement
60 56.0 Total hip replacement
54.2
Hip fracture surgery
Total DVT incidence (%)
50 48.0 46.8
40.2
40
34.0
30.6
30 27.0
24.0
22.1
20 16.0
12.5
7.9
10 4.8
0
Placebo/control ASA Warfarin LMWH Fondaparinux
Geerts et al. Chest 2001; Turpie et al. Arch Intern Med 2002
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RISCHIO EMORRAGICO
stratificazione del Rischio
multifattoriale paziente-procedura
3
Omran H, Bauersachs R, Rübenacker S, Goss F, Hammerstingl C. R. Pisters, D. A. Lane, R. Nieuwlaat, C. B. De Vos, H. J. G. M. Crijns, and G. Y. H. Lip,
The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. “A novel user-friendly score (HASBLED) to assess 1-year risk of major bleeding in
Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). patients with atrial fibrillation: the euro heart survey,”
Thromb Haemost 2012; 108:65–73. Chest, vol. 138, no. 5, pp. 1093–1100, 2010.
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RISCHIO EMORRAGICO
stratificazione del Rischio
multifattoriale paziente-procedura
the American College of Chest Physicians (ACCP) guidelines
alto
> 1.5%
basso
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! Chirurgia cutanea
! Cataratta con anestesia topica
! Artrocentesi ed iniezione dei tessuti molli
! Cateterismi, punture di vene, arterie superficiali
! Puntura sternale e biopsia osteomidollare
! Ecografia cardiaca transesofagea
! Procedure odontoiatriche semplici (≤ 2 elementi dentari)
! Procedure gastroenterologiche semplici
! Broncoscopia
! Rimozione di catetere venoso centrale
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EMATOMA SPINALE
Rara e potenzialmente catastrofica complicanza dell’anestesia neuroassiale;
1/150.000 epidurali e 1/220.000 spinali (0,00045%);
Di solito avviene nello spazio peridurale a seguito della puntura accidentale del
plesso venoso epidurale;
Si presenta con un progressivo blocco motorio (68%), disturbi intestinali (8%);
Fondamentali la diagnosi e il trattamento precoci per un pieno recupero;
Intervento neurochirurgico di
decompressione dell’ematoma.
Clinica reversibile se
decompressione entro le 8-12
ore.
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The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown.
Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal
anesthetics, recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient
populations.Overall, the risk of clinically significant bleeding increase with age, associated abnormalities of the spinal cord or vertebral
column, the presence of an underlying coagulopathy, difficulty during needle placement,and an indwelling neuraxial catheter during
sustained anticoagulation (particularly with standard heparin or low-molecular weight heparin). The need for prompt diagnosis and
intervention to optimize neurologic outcome is also consistently reported. In response to these patient safety issues, the American Society
of Regional Anesthesia and Pain Medicine (ASRA) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation.
Practice guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a prospective
randomized study, and there is no current laboratory model. As a result,the ASRA consensus statements represent the collective
experience of recognized experts in the field of neuraxial anesthesia and anticoagulation. These are based on case reports, clinical series,
pharmacology,hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is essential to patient
management.
EMATOMA SPINALE
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Profilassi meccanica
Calza elastica a compressione graduata
• A leggera 10-14 mmHg – 13 19 hPa
• 1 leggera 18-21 mmHg – 20-28 hPa
• 2 moderata 23-32 mmHg – 31-43 hPa
• 3 forte 34-46 mmHg – 45-61 hPa
• 4 molto forte >49 mmHg – > 65 hPa
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La compressione pneumatica
intermittente (130mmHg, ogni 20 sec,
durata impulso pressorio 1-3 sec)
garantisce il meccanismo di pompa
fisiologica.
In associazione alle EBPM rappresenta un
approccio ragionevole alla profilassi di TEP
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ANTICOAGULANTI
XII XIIa
TISSUE FACTOR
IX IXa
VIII VIIIa
X Xa
V Va
II IIa
FIBRINOGEN FIBRIN
VIA INTRINSECA
(CONTATTO SUPERFICIE) VIA ESTRINSECA
(DANNO TISSUTALE)
XII XIIa
TISSUE FACTOR
IX IXa
VIII VIIIa
X Xa
LMWH & Heparin
V Va
II IIa
FIBRINOGEN FIBRIN
VIA INTRINSECA
(CONTATTO SUPERFICIE) VIA ESTRINSECA
(DANNO TISSUTALE)
XII XIIa
TISSUE FACTOR
IX IXa
VIII VIIIa
X Xa
LMWH & Heparin
V Va
VKA
II IIa
FIBRINOGEN FIBRIN
VIA INTRINSECA
(CONTATTO SUPERFICIE) VIA ESTRINSECA
(DANNO TISSUTALE)
XII XIIa
TISSUE FACTOR
IX IXa
VIII VIIIa
O
_ II + _
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COSOO
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OSO O CH
ENF O
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_
3
NHSO
_O
3
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HN
C
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NHSO
_ O
3
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_
3
NHSO
_ O
3
NHSO
_
3 15000 Dalton
3
O
CH
terapia anti-tromboembolica
Protocolli Standardizzati
Enoxaparina 40mg OD
10-12h 4-12h
X Rimozione X
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terapia anti-tromboembolica
Protocolli Standardizzati
24h 4-12h
X Rimozione X
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Warfarin
•Inibisce la produzione epatica di fattori vitamina K dipendenti
i co
•Diminuisce il rischio di TVP rispetto ai non trattati
m bin
o t ro
•Necessita costante monitoraggio INR (da mantenere prtra 2 e 3) o tempo di
e sso
protrombina
m p l
c o
, la dimissione con controlli seriati
C
•La profilassi va continuata anche Fdopo
P
della coagulazione t K,
: v i
T O
ID O
•Rischio di complicanze emorragiche: 1,5- 5 %
T
AN con FANS aumenta il rischio di ulcere peptiche emorragiche
•Combinazione
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Rischio Rischio
Alto Basso
10% <5%
Bridging No Bridging
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Rischio
intermedio
5<RISCHIO<10%
Procedure ad elevato rischio di
sanguinamento
No Bridging
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Fondaparinux
•Pentasaccaride sintetico •Trombocitopenia (50000-100000/
ml)
•Inibitore specifico del fattore Xa
•Controindicato in pazienti con
•Lega antitrombina III
ot o clearance della creatinina inferiore a
n t i d 30 ml/min
un farmaco innovativo ed alternativo è
a
stato il fondaparinux che però ha molte
o
N da 6 ore •Controindicato nei pazienti anziani e
•Da assumere a partire
a g i e
nei pazienti a basso peso corporeo
dopo l’intervento
o
•Necessità rrdi monitoraggio
•Non aumenta l’attività fibrinolitica E m
dell’ematocrito, della conta
piastrinica, della creatinina sferica
•Profilassi per 7 giorni •Posologia profilassi: 2.5mg/die 6h
•Complicanze emorragiche (+++ in dopo per 5-9gg (1,5 mg/die in
seguito alla prima dose) insuff. ren. cronica)
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Anticoagulanti orali
FA NON COMPLICANZE
VALVOLARE TROMBO
PREVENZIONE EMBOLICHE
STROKE DOPO ACS
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DABIGATRAN
220 mg OD
or
150 mg OD
per pazienti >75 anni o con insufficienza renale moderata
RIVAROXABAN
10 mg OD
Start: 6-10h postop
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APIXABAN
2.5 mg BID
Start: 12-24h postop
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profilassi TEV
fibrillazione atriale
warfarin dabigatran rivaroxaban apixaban
Time t
72-96 h 2h 2.5-4 h 3h
peak activity
EBPM
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profilassi TEV
fibrillazione atriale
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Chirurgia Elettiva: quando e come sospendere?
6
5
1.6%
3.1%
Emivita
4 6.2%
3 12%
2 25%
1 50%
NAO
pratica clinica
Chirurgia Elettiva: quando e come sospendere?
RIPRODUCIBILITA’
93%
VKA 1 2 3 4 5
13
rivaroxaban: 3 giorni
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Chirurgia Elettiva: quando e come sospendere?
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Chirurgia Elettiva: quando e come sospendere?
anestesia spinale
Elevato Rischio
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Chirurgia Elettiva: quando riprendere?
una volta raggiunta un’adeguata emostasi chirurgica
NAO ripreso il prima possibile
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Esami di laboratorio:
P quali sono utili oggi?
con T…
cen proPT ratio
tra lung
zioConcentrazione
am
ne e n
dip to
end
Reagente
ent
e
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Chirurgia Elettiva: quando riprendere?
una volta raggiunta un’adeguata emostasi chirurgica
NAO ripreso il prima possibile
LMWH 24 NAO
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Laboratory Testing
New anticoagulants: A concise review
Apixaban has a mechanism of action similar to rivaroxaban with direct inhibition of factor Xa. Apixaba
variability in the PT depending on the reagents used in testing. The linear correlation of the plasma co
Baumann Kreuziger, Lisa M. MD; Morton, Colleen T. MBBS;
standardized to apixaban or to low-molecular-weight heparin are equally strong (r = 0.967). Therefore
Dries, David J. MSE; MD
necessary to determine the degree of anticoagulation with apixaban.32
Figure 2. Management guideline for bleeding while taking dabigatran, rivaroxaban, or apixaban.
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GUIDELINES
Background and objectives Performing neuraxial anaesthesia catheters can be placed the night before surgery. Regional a
Table 2 Recommended time intervals before and after neuraxial puncture or catheter removal
in patients receiving antithrombotic drugs is controversial due to anaesthesia in patients receiving full anticoagulation treatment
the increased risk of spinal epidural haematoma. StrictTime before continues to be contraindicated.
puncture/catheter Time after Catheter manipulation and
puncture/catheter
adherence to the recommended time intervals between the
manipulation removal carry similar risks
or removal to insertionorand
manipulation the same criteria
removal Laboratory tests
administration of anticoagulants, neuraxial blockade and the should apply. Appropriate neurological monitoring is essential
Unfractionated
removal of cathetersheparins (for prophylaxis,
is thought to improve patient safety4-6andh during the postoperative 1 hrecovery period and following catheter Platelets during treatment for more
!15 000
reduce IU per
the risk day)
of haematoma. Appropriate guidelines have been removal. The final decision to perform regional anaesthesiathan in 5 days
Unfractionated
prepared by a numberheparinsof(for treatment)
national societies of i.v. 4–6 h patients receiving drugs1that h affect haemostasis has to beaPTT, taken ACT, platelets
anaesthesiologists, but they do not have universal acceptance. s.c. 8–12 h after careful assessment 1 hof individual risks and benefits.
b
Low-molecular-weight
The introduction of newheparins (for prophylaxis
anticoagulants )
together with 12 h
recent 4h
Eur J Anaesthesiol 2010;27:999–1015 Platelets during treatment for more than 5 days
Low-molecular-weight
reports of stent thrombosis heparins (for treatment)
in patients 24 h
with perioperative Published online 1 October42010 h Platelets during treatment for more than 5 days
Fondaparinux (for prophylaxis,
cessation of antiplatelet drugs have2.5 considerably
mg per day) broadened36–42 theh 6–12 h (anti-Xa, standardised for specific agent)
Keywords: apixaban, aspirin, bleeding, cilostazol, clopidogrel, dabigatran,
Rivaroxaban
issue and made (forrevision
prophylaxis, 10 mg
necessary. Toq.d.) 22–26inh
overcome deficiencies 4–6 h heparin, hirudin, idrabiotaparinux,
epidural, fondaparinux, haematoma, (PT, standardised for specific agent)
Apixaban (forapplicability,
prophylaxis,the2.5European
mg b.i.d.)Society of 26–30 h low-molecular-weight heparin,
4–6 hprasugrel, regional anaesthesia, ?
content and rivaroxaban, spinal, ticagrelor
Dabigatran (for prophylaxis,
Anaesthesiology has taken the 150–220
initiative mg) Contraindicated
to provide current and according 6h ?
comprehensive guidelines for the continent as a whole.
to the manufacturer
Abbreviations: ACCP, American College of Chest Physicians; ACT,
Coumarins INR !1.4 Activated Clotting Time; ADP, Adenosine Diphosphate; aPTT, Activated
After catheter removal INR
Methods Extensive review of the literature. Partial Thromboplastin Time; ASRA, American Society of Regional
Hirudins (lepirudin, desirudin) 8–10 h Anesthesia; DVT, Deep Venous 2–4 h
Thrombosis; aPTT,
ECT, Ecarin Clotting Time; ESA, ECT
Results and c conclusions In order to minimise bleeding European Society of Anaesthesiology; ESC, European Society of
Argatroban 4h 2h aPTT, ECT, ACT
complications during regional anaesthetic techniques, care Cardiology; FDA, US Food and Drug Administration; HIT, Heparin-Induced
Acetylsalicylic acid None None Normalised Ratio; LMWH, Low-
Thrombocytopenia; INR, International
should be taken to avoid traumatic puncture. If a bloody tap
Clopidogrel 7 days After catheter
Molecular-Weight Heparin; NSAIDS, removal
Non-Steroidal Anti-Inflammatory Drugs;
occurs when intraoperative anticoagulation is planned, PCC, Prothrombin Complex Concentrates; PF4, Platelet Factor 4; PDE,
Ticlopidine 10 days After catheter
Phosphodiesterase; PT, Prothrombin removal
Time; SSRI, selective serotonin uptake
postponing
Prasugrel surgery should be considered. Alternatively,
7–10 days inhibitor; UFH, Unfractionated 6 hHeparin;
after catheter removal
VTE, Venous Thromboembolism
Ticagrelor 5 days 6 h after catheter removal
c
Cilostazol 42 h Background 5 h after catheter removal
The editors would like to thank Alain Borgeat
NSAIDs None None
The first national recommendations on neuraxial anaes-
(Switzerland), Elisabeth Gaertner (France, ESA Scien- thesia and antithrombotic drugs were published by
tificactivated
ACT, subcommittee 8), Daniela
clotting time; Filipescu
aPTT, activated (Romania,
partial thromboplastin the
time;German
b.i.d., twice daily; ECT,
Society ecarin clotting time;
for Anaesthesiology andINR, international normalised ratio; IU, international unit;
Intensive
i.v.,ESA ScientificNSAIDs,
intravenously; subcommittee 6), anti-inflammatory
non-steroidal Klaus Görlinger drugs; s.c.,
Caresubcutaneously;
in 1997 1 q.d., daily.
followed by
a
All time
the intervals Society
American refer to patients
of with normal renal function. b Maximum
(Germany,dosages
ESA Scientific subcommittee 6), Markus c
prophylactic for low-molecular-weight heparins are listedRegional
in Table 3. Prolonged(ASRA)
Anesthesia time interval in patients
in 1998, 2
andwith hepatic insufficiency.
Belgian
W. Hollmann (Netherlands, ESA Scientific subcommit- 3
anaesthesiologists in 2000. Since then new anti-
tee 8), Susan Mallett (UK, ESA Scientific subcommit- coagulant agents have been introduced and more
tee 6), and Andrew F. Smith (UK, Chair of the ESA
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TRAUMATOLOGIA Urgente-Emergente:
LA LOCO REGIONALE?
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DABIGATRAN
4212 neuraxial blocks - bleeding complications were not
different. No complications The first dose of dabigatran was
given at least 2 h after epidural catheter removal, and
patients who had undergone at least three attempts to place
spinal or epidural anesthesia or in whom the placement was
traumatic were excluded
Rosencher N, Noack H, Feuring M, et al. Type of anaesthesia and the safety and efficacy of
thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled
analysis of three randomized controlled trials. Thromb J 2012; 10:1–9.
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RIVAROXABAN
Neuraxial anesthesia was allowed within the RECORD licensing
protocols. None of the 1141 patients who were given rivaroxaban
and had neuraxial anesthesia developed a spinal hematoma. In total,
608 epidural catheters were used. Rivaroxaban was paused for 22–
26 h before the removal of the catheters and the next rivaroxaban
dose was given 4–6 h after catheter removal
Rosencher N, Llau JV, Mueck W, et al. Incidence of neuraxial haematoma after total hip or knee
surgery: RECORD programme. Acta Anaesthesiol Scand 2013; 57:565–572
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APIXABAN
No epidural hematoma was reported in the licensing trials. Epidural
catheters had to be removed 5 h before the first dose of Apixaban. If
Apixaban is given in this prophylactic dose and catheters are in place,
expert recommendations to wait for epidural catheter removal after
the last dose of prophylactic Apixaban range from 20 to 30 h
Waurick K, Riess H,Van Aken H, et al. S1 guideline neuraxial regional anesthesia and
thromboprophylaxis/antithrombotic medication. Anästh Intensivmed 2014; 55:464–492
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D. Imberti et al.
pratica Sospensione
clinicadei NAO?
Table 4. Bleeding risk of surgical interventions.