TVP ed Embolia Polmonare: Definizione

TVP Sintomi & Segni NON SPECIFICI o ASSENTI Dolore Tensione Edema DD: crampi o strappi muscolari, rottura cisti poplitea, contusioni, artriti anca-ginocchio, gotta, tendiniti.

EP Sintomi & Segni NON SPECIFICI, dipendono da: Entità dell’ostruzione Rapidità dell’ostruzione Vaso-broncocostrizione associata Stato cardiopolmonare preesistente

EP:Ostruzione completa e rapida Sincope Shock Ipotensione prolungata Diagnosi urgente Diagnosi differenziale: Infarto miocardico, Tamponamento cardiaco, Emorragia massiva, Setticemia, Pneumotorace, Aneurisma dissecante

Ostruzione parziale Sintomi* Segni* Dispnea Dolore toracico Tosse Dolore AAII Tachipnea (>20 min) Rantoli (crepitii) Tachicardia IV tono * Più frequenti Diagnosi differenziale (dispnea): Polmonite, Ostruzione vie aeree, Pneumotorace, Edema polmonare, Atelettasia

ECG Diagnosi Differenziale: IMA Negativo Suggestivo per EP (emodinamicamente significativa): Sottoslivellamento ST Inversione onda T Nuovo Blocco di branca dx S1Q3T3 non preesistente

Rx torace Spesso Negativo Esclude: Pneumotorace Aneurisma aorta Altro Alterazioni Non-specifiche

Emogasanalisi Ridotta PO2: aspecifica Puntura Arteriosa: Attenzione! Normale nel 10-15% di EP

Presentazione Esami semplici (Sintomi e segni) Sospetto clinico Situazione clinica Anamnesi

Situazione clinica Anamnesi Periodo Postoperatorio Trauma arti inferiori Allettamento Gravidanza/puerperio Neoplasia Pregresso VTE Trombofilia Famigliarità Estroprogestinici

Sospetto clinico EP DEBOLE FORTE Solo agitazione + tachicardia + dipnea non spiegabile + storia di tromboembolismo venoso + trombofilia famigliare + estroprogestinici + recente trauma arti inferiori + allettamento FORTE

Trattamento Sospetto clinico Diagnosi

Sospetto clinico UFH Bolo (5.000 IU or 80 IU/kg IV)

 3 alta 1-2 moderata <1 bassa SCORE di Wells 1 -2 Neoplasia in fase attiva (trattamento in corso o nei 6 mesi precedenti o palliativo) Paralisi , paresi o recente immobilizzazione degli arti inferiori Chirurgia maggiore nelle 4 settimane precedenti o paziente allettato e da poco rimesso in piedi Gonfiore localizzato lungo la distribuzione del sistema venoso profondo Gonfiore di tutta la gamba Gonfiore del polpaccio > 3 cm rispetto all’arto asintomatico (misurati 10cm sotto la tuberosità tibiale) Edema con fovea maggiore nell’arto interessato Vene collaterali superficiali (non varicose) Diagnosi alternativa altrettanto o più probabile della TVP  3 alta 1-2 moderata <1 bassa

Diagnosi D-dimero CUS Ecocolordoppler TAC spirale Clinica + Angiografia polmonare Scintigrafia v/p Clinica +

Scintigrafia perfusoria

Risonanza magnetica

Risonanza magnetica

Angiopneumografia

Flebografia

TRATTAMENTO

Anticoagulant drugs in the treatment of pulmonary embolism: a controlled clinical trial Patients with PE (clinical signs, EKG, chest x-rays) Treated group: heparin 10.000 U IV every 6h for 36 h plus nicoumalone, orally for 14 days Trial terminated after randomization of 35 patients Among 19 control pts, 5 fatal (autopsy-verified) and 5 nonfatal recurrent PE Among 16 treated pts, 1 death from pneumonia and a bleeding duodenal ulcer Barritt, Lancet 1960

A.T.H.O.S Randomized trial comparing heparin plus acenocoumarol (n=60) with acenocoumarol alone (=60) in proximal vein thrombosis Brandjes, N Engl J Med 1992

LMWH vs standard heparin in proximal DVT -85 patients in each group, follow-up 6 mo. -No difference in bleeding complications Prandoni, Lancet 1992

Koopman et al. N Engl J Med 1996

The Columbus investigators. N Engl J Med 1997

Gould et al. Ann Intern Med 1999 Major bleeding complications occurred in 1.9% of the participants treated with unfractionated heparin. The results of seven studies favored low-molecular-weight heparins for this outcome; one study (3) demonstrated a statistically significant advantage (Figure 1 ). For all studies combined, we obtained different results depending on the statistical model and the measure of treatment effect. When the fixed-effects model was used, the odds ratio for major bleeding favored low-molecular-weight heparins (0.57 [95% CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, 0.04% to 1.26%]; P = 0.07; NNT, 164). When the random-effects model was used, we did not detect a statistically significant difference between treatment groups in the frequency of major bleeding complications (odds ratio, 0.71 [CI, 0.40 to 1.27]; P > 0.2). Gould et al. Ann Intern Med 1999

LMWH therapy in VTE Nadroparin calcium (Fraxiparine) 85 IU/kg q12h or 170 IU/kg/d Enoxaparin sodium (Clexane) 100 U/kg q12h (1mg/kg q12h or 1.5 mg/kg/d) Dalteparin sodium (Fragmin) 200 IU/kg/d Tinzaparin sodium 175 IU/kg/d

LMWH - Criteria for early discharge or outpatient therapy Patient in stable condition Patient willingness to collaborate Low bleeding risk and normal renal function Oral anticoagulant surveillance facilities Early medical contact facilities

Baseline lab in suspected VTE APTT, PT-INR, CBC Sceening for thrombophylia in selected patients (idiopathic VTE, transient risk factors but age < 50 years, recurrent VTE, positive family history) Antithrombin III, Protein C, Protein S, APC resistance, Factor V Leiden, Prothrombin G210A, homocysteinemia, lupus anticoagulant, antiphospholipid antibodies (anti-beta-2-glycoprotein I)

Heparin - VTE UFH Bolus (5.000 IU or 80 IU/kg IV,suspected VTE) UFH: maintenance infusion 30-35.000 IU IV/SC or 18 IU/kg/h; appropriate dosage of LMWH UFH: Lab after 6h to keep aPTT 1.5-2.5 times the control Check platelet count between days 3 to 5 Start warfarin at day 1 at 5 mg/day Continue both drugs at least 5 days Stop heparin when INR>2 fot 2 consecutive days Continue warfarin to keep INR between 2.0 and 3.0

A study demonstrated that recurrent VTE is infrequent if continuous IV heparin is administered in doses Adjusted to prolong the APTT > 1.5. Basu D et al., N Engl J Med 1972 Blood heparin level of at least 0.2 IU/ml Heparin infused IV in a dose of at least 1250 U/h

Heparin dose-adjustment nomogram APTT Bolus Hold Rate change (U/h) Repeat APTT < 50 50-59 60-85 86-95 96-120 > 120 5000 30 60 +120 -80 -160 6 h Next morn Next morn Cruickshank et al, Arch Intern Med 1991; 151:333

Weight-based nomogram Initial dose APTT, < 35 s (<1.2 x control) APTT, 35 to 45 s (1.2 to 1.5 x control) APTT, 46 to 70 s (1,5 to 2.3 x control) APTT, 71 to 90 s (2,3 to 3.0 x control) APTT, > 90 s (> 3 x control) 80 U/Kg bolus, then 18 U/Kg/h 80 U/Kg bolus, increase by 4 U/Kg/h 40 U/Kg bolus, increase by 2 U/Kg/h NO CHANGE Decrease infusion by 2 U/Kg/h Hold infusion 1 h, then decrease by 3U/Kg/h Raschke et al., Ann Intern Med 1993; 119:874

Thrombolytic therapy Usually not indicated in DVT Reserved to hemodinamically unstable patients with proven PE in the absence of bleeding risk

Duration of oral anticoagulant treatment First event associated with transient or reversible risk factors (patients may have underlying eterozygous factor V Leiden or prothrombin G20210A) 3-6 mo > 6 mo First event of idiopathic VTE. First event associated with permanent high risk factors (unresolved cancer, high risk thrombophilia) Recurrent VTE, idiopathic or associated with thrombophilia 12 mo or lifelong

Indications to inferior vena cava filters Contraindication/complication of anticoagulation in high risk patients Recurrent VTE despite adequate anticoagulation Pulmonary embolectomy or endarterectomy

Chronic thromboembolic pulmonary hypertension Not rare (2-5%?) Perfusion defects at pulmonary scan Proximal obstruction: pulmonary thromboendarterectomy Nonproximal obstruction: angioplasty