Lorenzo Loffredo

Sapienza Università di Roma

SIMPOSIOTromboembolismo venoso: nuove strategie terapeutiche

La trombosi venosa profonda non puòessere diagnosticata o esclusa sullabase di segni clinici.

Patologie che si manifestano con sintomi analoghi alla trombosi venosa profonda: 1. Ematoma muscolare2. Strappo o rottura del tendine d’Achille3. Borsiti o tenosinoviti4. Rottura di cisti di Baker5. Artriti6. Aneurisma femorale o popliteo7. Linfedema (primitivo o secondario)8. Linfangiti9. Infezione della cute e del sottocute (dermoipodermiti)10.Tromboflebite superficiale11.Insufficienza venosa cronica12.Sindrome post-flebitica13.Insufficienza cardiaca destra14.Strappo muscolare15.Sciatalgia

thrombosis

Trombo-embolismo venoso (TEV)

Trombosi venosa

profonda

Embolia Polmonare

Cohen (Blood. 2012;120(8) 1562-1569):

Il TEV inizia nel cavopopliteo in più del 75% dei pazienti.

Tra

tto

dis

tale

Tra

tto

pro

ssim

ale

Diagnosi TVP

- Venografia

- Ecocolor doppler (CUS)

- RMN/TC

COMPRESSIONE

COMPRESSIONE

TROMBOSI

VENA

COMPRIMIBILE

Incomprimibilità vasale

compression ultra-sonography (CUS)

La valutazione ecografica viene eseguita comprimendo lavena con il trasduttore.

Posizione del pz

n.1

I Compressione

Distretto Vascolare dell’Arto Inferiore- anatomia -

CUS

I Compressione

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

Whole-Leg Ultrasonography(Whole leg strategy)

Altri tipi di CUS

3-points CUS

Vena ed Arteria Femorale- CUS -

AFC

VFC

CUS

Distretto Vascolare dell’Arto Inferiore- CUS -

AFC

CUS Negativa

CUS positiva per trombosi

1.Incomprimibilità vasale2.Aumento del diametro vasale3.Presenza di materiale ecogeno

nel lume4.Assenza di Flusso5.Fissità dei lembi valvolari6.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) examhas 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

- 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.

- 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.

PROS

- Preliminary results of subgroup analyses and meta-analyses of randomized clinical trials suggest that NOACs could represent analternative to conventional anticoagulation in patients withactive cancer.

- oral administration, fixed dose regimens and absence of heparin-induced thrombocytopenia

There are minimal clinical trial data to inform treatment of pa-tients 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 ad-justed 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 veinthrombosis.

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 internalmedicine wards.

Dipartimento di Medicina

Interna e Specialità Mediche

Sapienza Università di Roma.

AURELIO study