I Nuovi Anticoagulanti orali (NAO) nel trombo

SIMPOSIO
Tromboembolismo venoso: nuove strategie terapeutiche
Lorenzo Loffredo
Sapienza Università di Roma
La trombosi venosa profonda non può
essere diagnosticata o esclusa sulla
base di segni clinici.
Patologie che si manifestano con sintomi analoghi alla
trombosi venosa profonda:
1. Ematoma muscolare
2. Strappo o rottura del tendine d’Achille
3. Borsiti o tenosinoviti
4. Rottura di cisti di Baker
5. Artriti
6. Aneurisma femorale o popliteo
7. Linfedema (primitivo o secondario)
8. Linfangiti
9. Infezione della cute e del sottocute (dermoipodermiti)
10.Tromboflebite superficiale
11.Insufficienza venosa cronica
12.Sindrome post-flebitica
13.Insufficienza cardiaca destra
14.Strappo muscolare
15.Sciatalgia
Trombosi venosa
profonda
Embolia Polmonare
thrombosis
Tratto distale
Il TEV inizia nel cavo
popliteo in più del 75%
dei pazienti.
Tratto prossimale
Trombo-embolismo venoso (TEV)
Cohen (Blood. 2012;120(8) 1562-1569):
Diagnosi TVP
- Venografia
- Ecocolor doppler (CUS)
- RMN/TC
Incomprimibilità vasale
COMPRESSIONE
La valutazione ecografica viene
eseguita comprimendo la
vena con il trasduttore.
VENA
COMPRIMIBILE
COMPRESSIONE
TROMBOSI
compression ultra-sonography (CUS)
Posizione del pz
n.1
I Compressione
Distretto Vascolare dell’Arto Inferiore
I Compressione
- anatomia -
CUS
2-point or limited CUS
Posizione del pz
n.2
II Compressione
Distretto Vascolare dell’Arto Inferiore
- anatomia -
II Compressione
CUS
2-point or limited CUS
Altri tipi di CUS
3-points CUS
Whole-Leg Ultrasonography
(Whole leg strategy)
Vena ed Arteria Femorale
- CUS -
CUS
AFC
VFC
Distretto Vascolare dell’Arto Inferiore
- CUS -
AFC
CUS Negativa
CUS positiva per trombosi
1.Incomprimibilità vasale
2.Aumento del diametro vasale
3.Presenza di materiale ecogeno
nel lume
4.Assenza di Flusso
5.Fissità dei lembi valvolari
6.Presenza di circoli collaterali
Pooled sensitivity of 95% and specificity of 96%.
While a complete and
detailed scan of both
lower extremities is time
consuming, it is often not
needed and a 2-point
(common femoral vein
and popliteal vein) exam
has similar sensitivity
and specificity to detect
clinically important DVT
in the proximal veins
2-points CUS can
either be limited to
the proximal veins
and repeated within 1
week (serial limited
CUS) or extended to
both proximal and
distal veins and
performed on one
occasion (single
complete CUS)
(Whole leg strategy).
Repeat testing may
be safely avoided in
patients with a
normal D-dimer test
result at
presentation.
Algoritmo diagnostico/terapeutico
Trattamento della
TVP acuta
Coagulation process and targets of direct oral anticoagulants (DOACs).
Pierre Fontana et al. Eur Heart J 2014;eurheartj.ehu027
Absorption and metabolism of the different new anticoagulant drugs.
Hein Heidbuchel et al. Europace 2013;15:625-651
Dobesh Drugs (2014) 74:2015–2032
Dobesh Drugs (2014) 74:2015–2032
Loffredo L. Intern Emerg Med.
2015;10:499-506.
Loffredo L. Intern Emerg Med.
2015;10:499-506.
Loffredo L. Intern Emerg Med.
2015;10:499-506.
Van der Hulle J Thromb Haemost 2014; 12: 320–8.
International Journal of Cardiology, Volume 212, 2016, 255–258
There are no specific trials that examine the efficacy of
the NOACs in inherited or acquired thrombophilias although
numerous patients with undiagnosed thrombophilia
would have been enrolled in the studies.
antiphospholipid syndrome (APS)
?
LMWH and VKA treatment to a target INR of 2–3
NO heparin-induced thrombocytopenia/osteoporosis
non-heparin parenteral anticoagulant
Pro
Verso M. Intern Emerg Med 2015
Larsen PLoS One. 2014 Dec 5;9(12):e114445.
CONS
PROS
- Hormonal therapy and tyrosine-kinase
inhibitors are inhibitors of P-glycoprotein
and CYP 3A4 way, whereas doxorubicin,
vinblastine and dexamethasone are inducers
of P-glycoprotein and CYP 3A4.
- Preliminary results of subgroup
analyses and meta-analyses of
randomized clinical trials suggest that
NOACs could represent an
alternative to conventional
anticoagulation in patients with
active cancer.
- lack of clinical trials concerning head to
head comparison in terms of efficacy and
safety profiles between LMWHs and NOACs
in long-term treatment of VTE of patients
with cancer.
- oral administration, fixed dose
regimens and absence of heparininduced thrombocytopenia
There are minimal clinical trial data to inform treatment of patients with weights > 100 kg.
A fixed-dose regimen of NOACs may not provide sufficient
anticoagulant effect to obese patients and may provide
supratherapeutic doses to underweight individuals.
A subgroup evaluation of AMPLIFY and EINSTEIN study did
demonstrate improved safety of apixaban compared with
warfarin in those weighing > 100 kg.
These patients should be treated acutely with full-dose weight adjusted LMWH monotherapy.
In pregnancy, this is based on teratogenicity of VKAs and lack of safety
data for NOAC’s .
VKAs and LMWH are safe for breastfeeding .
There are no specific trials that examine the efficacy of the
NOACs in distal DVT, splanchnic, cerebral vein
thrombosis.
Renal failure, defined by a CrCl < 30 ml/min, was an exclusion in all of
the NOAC trials (AMPLIFY excluded patients with a CrCl < 25 ml/min).
Beware for NOACs in patients with CrCl 30–50 ml/min if we feel they
have risk factors for worsening renal function (i. e. poorly controlled
hypertension or diabetes, frail elderly).
Conclusioni
-
La CUS è una metodica altamente sensibile e specifica
per diagnosticare la TVP.
-
La sua facilità di esecuzione ne permette un ampio uso
per la diagnosi e la prevenzione delle complicanze
trombo-emboliche.
-
I NOACs rappresentano una valida alternativa agli
antagonisti della vitamina K nel trattamento del TEV.
-
Rispetto agli inibitori della vitamina K presentano una
riduzione del rischio di sanguinamento.
-
Ulteriori studi sono necessari per valutare l’efficacia dei
NOACs in alcune categorie di pazienti, come quelli
affetti da neoplasia, insufficienza renale severa,
trombofilia, obesità severa, trombosi venose distali o
soggetti in stato gravidico.
rAte of venoUs thRombosis in
acutEly iLl patIents
hOspitalized in internal
medicine wards.
AURELIO
study
Dipartimento di Medicina
Interna e Specialità Mediche
Sapienza Università di Roma.