Tromboza venoasa profunda-o provocare terapeutica

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Diagnosticul si tratamentul TVP nu sunt intotdeauna usor de realizat. Din constelatia de antitrombotice, alegerea schemei si dozajului terapeutic pentru liza trombusului si/sau preventia secundara, pune serioase probleme in practica medicala

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Tromboza venoasa Tromboza venoasa profundaprofunda

o provocare terapeutica

Andritoiu Alexandru*, Silosi Cristian**

Spitalul Clinic de Urgenta Militar Craiova*Sectia Medicina Interna

** Clinica Chirurgie

TVPTVP

• The precise number of people affected by DVT/PE is unknown, but estimates range from 300.000 to 600.000 (1 to 2 per 1000, and in those over 80 years of age, as high as 1 in 100) each year in the United States.

• Estimates suggest that 60.000-100.000 Americans die of DVT/PE (also called venous thromboembolism).

• Among people who have had a DVT, one-half will have long-term complications (post-thrombotic syndrome)

TVP - Complicatiile TVP - Complicatiile tardivetardive

• Sdr. post-trombotic

• TEP recurent

Metode de diagnostic Metode de diagnostic flebologicflebologic

• Clinic• D-dimeri• US• Venografie• Isotopi• Angio-CT/RMN

USUS• B-mode• Doppler color• Doppler spectral• Power-angio• B-flow• CEUS• Elastografie

FLEBOGRAFIA – ,,gold standard,,

FlebografiaFlebografia

In cazuri selectionate!

US Doppler TVP-V. popliteeUS Doppler TVP-V. poplitee

Flux absent in vena popliteeFlux prezent in artera homolaterala

Scorul WellsScorul Wells

TVP in situatii clinice particulareTVP in situatii clinice particulare

• Sarcina/trombofilie• Neoplazii• Arterite inflamatorii• Repaus prelungit la pat (Stroke, IMA)• Post chirurgical (pelvis, abdomen, ortopedie)• Gonartroza• Cateterism venos• Droguri cu risc inalt• Medicamente cu risc pro-trombotic

Obiectivele terapieiObiectivele terapiei

• Dizolvarea trombusului

• Prevenirea extensiei proximale

• Prevenirea recurentei TVP

• Prevenirea/tratamentul TEPA

• Prevenirea sdr. post-trombotic

Mijloace terapeuticeMijloace terapeutice

Farmacologice• anticoagulante• antiagregante• tromboliticeMecanice• fragmentarea trombusului• trombo-suctiuneaHemodinamice• Contentia in ciorap elastic

Heparina nefractionataHeparina nefractionata

LMWH/FondaparinaLMWH/Fondaparina

TVP cu TEPATVP cu TEPA

TVP in neoplaziiTVP in neoplazii

Mecanism auto-imun (asociata cu tromboza a/v 30-50% cazuri)

Agenti anticoagulanti alternativiAgenti anticoagulanti alternativi

• Fondaparina• Danaparoid• Lepirudin• Argatroban

ContraindicatiiContraindicatii

Risc mai redus de sangerareRisc mai redus de sangerare

Indicatii/ContraindicatiiIndicatii/Contraindicatii

Profilaxia primara

• Preoperator • Antiagregante • LWMH

Antiagregantele plachetareAntiagregantele plachetare

• In profilatia TVP

Direct comparisons of proportional effects of different antiplatelet regimens on deep venous thrombosis and on pulmonary embolism

BMJ 1994;308:235-246

Proportional effects of antiplatelet therapy on numbers of patients observed to have pulmonary embolism in trials that sought venous

thrombosis systematically after general and orthopaedic (traumatic and elective) surgery and in high risk medical patients

BMJ 1994;308:235-246

  15 April 2000;Volume 355, Issue 9212, Pages 1295 - 1302,

Aspirin reduces the risk of pulmonary embolism and deep-vein thrombosis by at least a third throughout a period of increased risk.

There is now good evidence for considering aspirin routinely in a wide range of surgical and medical groups at high risk of venous thromboembolism.

Triflusal

• selective inhibition of TxB2 and platelet cyclo-oxygenase activity

• does not interfere significantly with endothelial synthesis of prostacyclin via the cyclooxygen ase-2 pathway.

• increases nitric oxide synthesis by neutrophils, and decreases the activity of nuclear transcription factor NF-B more than aspirin does

• inactivates intraplatelet phosphodiesterase • potentiates the antiaggregant effect of cAMP and

cGMP • These pharmacological differences make triflusal

potentially more effective and safer than aspirin

Triflusal appears to provide prevention of thromboembolic risk to patients who have undergone hip surgery, particularly total hip replacement

The amount of blood transfused was significantly reduced in triflusal compared with aspirin recipients who underwent hip surgery.

Risk of haemorrhage was also reduced in patients receiving triflusal versus aspirin.

Atentie!Atentie!

• Dovezi certe in preventia Stroke-FibA!

• Ghidurile nu recomanda Triflusal in TVP!

Profilaxia recurentei Profilaxia recurentei TVP/EPTVP/EP

• Antiagregante

• LWHM

• Anticoagulante dicumarinice

• NOAC

Risk-Assessment Model for Venous Thromboembolism According to the Khorana Score

Connors JM. N Engl J Med 2014;370:2515-2519

Comparison of Recommendations regarding Prophylaxis against Venous Thromboembolism

Connors JM. N Engl J Med 2014;370:2515-2519

Profilaxia secundaraProfilaxia secundara (dicumarinicele)(dicumarinicele)

Long-term therapy• Coumadin

(warfarina)• Acenocumarol

(sintrom, trombostop)

• Reduce riscul de recurenta >90%

• INR optim 2-3• Risc de sangerare

3% /an

Profilaxia secundara Profilaxia secundara NOACNOAC

Trombofilia / Riscul de recurentaTrombofilia / Riscul de recurenta

Durata proxilaxiei secundareDurata proxilaxiei secundare

Raportul risc de recidiva/risc de sangerare

Experienta noastra

• Peste 50 cazuri TVP- dupa 2010• Prima cauza de deces in Sp. Militar Cva!• TEPA masiv – cauza de deces• Dupa interv. chirurgicale - abdomniale/pelvine - ortopedie - neoplazii

• +/- Asociate cu obezitatea

1. Case report1. Case report

T. Maria, 48 ani• Fibrom uterin• Tratament: Orgametril• Edem masiv m. inf. stg.

Fibromatoza uterin

Tromb masiv ocluziv in v. iliaca comuna stg

US DopplerUS Doppler

TVP - V. iliaca com. stgTVP - V. iliaca com. stg

Confirmare Angio-RMN

Ex. BiologiceEx. Biologice

• VSH 56-41 mm/h• Fibrinogen 440 mg/dL• CRP 4mg/dL• Hb 7.5 g/dL• Sideremie 7 microgr/dL• Tb 635.000 /mmc• CEA - negativ• CA 125 - negativ

Coagulograma• INR 2.5• TQ 35 sec• AP 20%• APTT 44 sec

Rezolutia trombozeiRezolutia trombozei

• Clexane 1mg/Kgc• Sintrom 2 mg• Aflen 300 mg• Detralex• Contentie elastica

Dupa 20 zile

Profilaxia recidivei/TEPAProfilaxia recidivei/TEPA

• Sintrom ¼ cp• Aflen 300 mg x 2• Detralex 2 x1 cp• Contentie elastica

Reevaluare la 3 luni• Fara tromboza US• Fara TEPA• INR 2.2-2.9

2. Case Report2. Case Report

S. Filofteia, 50 yr• 2009 TVP Fem-Popl stg• Repetate episoade EP• APP: hipercolesterolemie TRATAMENT• Sintrom 4mg• Aflen 1 cp/zi• Detralex 2 x 1 cp/zi• Endolex 2 x 1 cp/zi• Lioton gel – local• Sortis 20 mg/zi

• VSH 21-50-125-60-37• D-dimeri pozitivi• Colesterol 325• LDL-Col178 mg/dL• HDL-Col 56 mg/dl• CRP pozitiva• Proteina S 31% (55-140)• Proteina C 57% (70-130)• AT III122% (>80)

3. Case report3. Case report

A. Emil, 42 yrA. Emil, 42 yr• Iulie 2008- TVP-V. popl stg.• Febr. 2010: TVP Fem-Popl dr. TEPA

masiv• ECG: RS, Ax QRS la dreapta, T neg

anterior• Doppler: tromboza profunda ax

venos femuro-popliteu dr• D-dimeri pozitivi• Angio CT: coronare permeabile Tromb rezidual non-ocluziv A

pulmonara dr

• Tratament• Sintrom 2 mg/zi• Aflen 1 cp/zi• Detralex 2 x 1 cp/zi• Venoruton, gel-local

• Rezolutia trombului -6 luni

• Fara recidiva TEPA• A sistat tratam.

antitrombotic dupa 12 luni!

4. Case report4. Case report

D. Adriana, 43 yr

• Edem masiv m. inf.dr.

• Internare Chir. Sp. Jud

• Tratatment: Sintrom - INR 2.8!

• 2 sapt.- Recidiva edemului!

• Reinternare Sp. Mil.

• D-dimeri pozitivi

Doppler-Elastografia TVPDoppler-Elastografia TVP

TVP F-P dr. – la 2 sapt. de la debut (recidiva sub Sintrom)

QUIZ

Care este cea mai buna solutie terapeutica?

• Pastrarea Sintrom (INR optim) si expectativa

• Adaugare anti-agregant

• Inlocuirea Sintrom cu NOAC

• Tratament interventional

Tratament

In spital• Heparina nefractionata 1000 UI/h (25.000 Ui/zi)-72 h• Clexane s.c -5 zile• Clexane+Sintrom 3 zile• Externare: edem redus Tratament la domiciliu• Sintrom 2mg/z• Aflen 300 mg/z• Detralex• Contentie elastica• INR la 1 L• Reevaluare Doppler-Elasto+D-dimeri+INR la 1-3 luni

Concluzii

• TVP – ramane o provocare terapeutica• Multiple optiuni terapeutice antitromboticeImportant:• Localizarea trombusului• Vechimea trombusului• Atingerea raportului Risc/Beneficiu optim (la limita

sangerarii!)• Raport cost-eficienta (tratament 6L-24 L)

Combinatia ACO+Antiagregant

• Potenteaza efectul antitrombotic

• Permite reducerea dozelor de ACO

• Dupa 3 luni - doar antiagregant• Fara recidiva trombotica• Fara recidiva embolica• Fara risc major de sangerare