Tratamiento del Tromboembolismo Venoso

1. Tratamiento del Tromboembolismo Venoso El Montanyà, Seva 2013 Sesión III: ETEV en las guías del ACCP 2012: revisión crítica basada en los casos clínicos X Curso de Formación Continuada

3. Resumen de indicaciones sobre duración de la anticoagulación con AVK en el TEV, realizado a partir de las recomendaciones o sugerencias de la 9ª edición de las Guías de Tratamiento Antitrombótico del ACCP. La mayoría de las recomendaciones son de grado 1B o 2B La intensidad recomendada es de un INR 2-3

4. Recomendamos que los pacientes con una EP o una TVP proximal no-provocada deben ser tratados durante 3 a 6 meses. Recomendamos que en mujeres con TEV asociado a tratamiento hormonalno se requieren anticoagulaciones superiores a 3 meses, siempre que el tratamiento hormonal haya sido suspendido en el momento del diagnóstico. Recomendamos que las mujeres con TEV asociado a terapia hormonal interrumpan el tratamiento hormonal (anticonceptivos orales y terapia estrogénica substitutiva) antes de suspender la terapia anticoagulante. Sin embargo, en las mujeres premenopáusicas debe utilizarse una anticoncepción alternativa eficaz para evitar la toxicidad potencial de la exposición fetal temprana a la warfarina. Sugerimos que en pacientes seleccionadas la terapia hormonal puede ser continuada si hay una fuerte indicación clínica para dicho tratamiento. En estos casos la terapia anticoagulante se debe continuar durante el período de mantenimiento de la terapia hormonal. Apuntes sobre recomendaciones en la duración de la anticoagulación en el TEV según el SCC de la ISTH Baglin. JTH 2012: 10: 698

5. Caso 1 • Mujer 24 años, sana, obesa: 106kg, anticonceptivos orales • 7 días antes: viaje transoceánico; unas semanas antes del vuelo refirió molestias sin limitación funcional de EEII • Motivo de consulta: molestias y aumento del perímetro MID • DD: 990 ng/mL (n<234) • ECOdoppler: TVP femoral superficial, poplítea y distal MID

6. Probabilidad clínica de TVP (Wells) Probabilidad clínica: <1: BAJA <1: IMPROBABLE 1 – 2: INTERMEDIA >2: PROBABLE >2: ALTA

7. Lo que dicen las guías • 3.3 In patients with a moderate pretest probability of first lower extremity DVT, we recommend one of the following initial tests: (i) a highly sensitive D-dimer or (ii) proximal CUS, or (iii) whole-leg US rather than (i) no testing (Grade 1B for all comparisons) or (ii) venography (Grade 1B for all comparisons) . We suggest initial use of a highly sensitive D-dimer rather than US (Grade 2C). • 3.4. In patients with a high pretest probability of first lower extremity DVT, we recommend either (i) proximal CUS or (ii) whole-leg US over no testing (Grade 1B for all comparisons) or venography (Grade 1B for all comparisons).

8. Técnicas de dímero D: especificidad y sensibilidad en el diagnóstico de TEV

9. Caso 1 • Stop anticonceptivos orales • Metrorragia a los 7 días de inicio de HBPM • A las 2 semanas inicio progesterona

10. Pregunta caso 1 • El día que presentó la metrorragia, ¿cual hubiese sido la mejor actuación respecto de la anticoagulación con HBPM? • Mantener la misma dosis de HBPM • Reducir la HBPM a dosis de profilaxis • Suspender alguna dosis de HBPM • Suspender la HBPM • Suspender la HBPM e iniciar AVK

11. Systematic review: case-fatality rates of recurrent VTE and major bleeding events among patients treated for VTE Carrier y col. Ann Intern Med 2010; 152: 578

12. Lo que dicen las guías • 2.1. In patients with acute DVT of the leg treated with vitamin K antagonist (VKA) therapy, we recommend initial treatment with parenteral anticoagulation (low-molecular-weight heparin [LMWH], fondaparinux, IV unfractionated heparin [UFH], or subcutaneous [SC] UFH) over no such initial treatment (Grade 1B). • 2.4. In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h (Grade 1B). • 2.5.2. In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration (Grade 2C) . Remarks: This recommendation only applies when the approved once-daily regimen uses the same daily dose as the twice-daily regimen (ie, the once-daily injection contains double the dose of each twice-daily injection). It also places value on avoiding an extra injection per day. • 2.7. In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital (Grade 1B).

13. Lo que dicen las guías • 2.14. In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest (Grade 2C). Remarks: If edema and pain are severe, ambulation may need to be deferred. We suggest the use of compression therapy in these patients. • 3.1.2. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B) , and (iii) extended therapy if there is a high bleeding risk (Grade 1B) . We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B). • 3.1.4. In patients with an unprovoked DVT of the leg (isolated distal [see remark] or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B) . After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy. • 3.1.4.1. In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B) .

14. Systematic review: case-fatality rates of recurrent VTE and major bleeding events among patients treated for VTE Carrier y col. Ann Intern Med 2010; 152: 578

15. Lo que dicen las guías • 3.2. In patients with DVT of the leg who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR , 2) or higher (INR 3.0-5.0) range for all treatment durations (Grade 1B). • 3.3.1. In patients with DVT of the leg and no cancer, we suggest VKA therapy over LMWH for long-term therapy (Grade 2C) . For patients with DVT and no cancer who are not treated with VKA therapy, we suggest LMWH over dabigatran or rivaroxaban for long-term therapy (Grade 2C). • 4.1. In patients with acute symptomatic DVT of the leg, we suggest the use of compression stockings (Grade 2B). Remarks: Compression stockings should be worn for 2 years, and we suggest beyond that if patients have developed PTS and find the stockings helpful.

16. Caso 3 • Mujer de 38 años, fumadora, S. ansioso-depresivo, endometriosis. Anticonceptivos orales (inicio 6 meses antes) • 2d antes dolor y aumento del perímetro infrapoplíteo MII • Es atendida por episodio sincopal, vegetatismo, disnea de inicio súbito posterior. • RS, TA: 100/60mmHg, FC:110 lpm, • ECG: S1Q3T3, DD: 10000 ng/mL, • Enoxaparina 1mg/kg y remisión a Hospital de referencia

17. Caso 3 En Hospital de referencia: • TA 100/60 mmHg, FC 105 lpm • SaO2: 99%, FG>60mL/min • Troponina I: 0.86ug/L (n:<0.2) • AngioTC: TEP masivo bilateral, signos sobrecarga D, signos sugerentes TVP poplítea bilateral • ECOcar TT: VD dilatado, ratio VD/VI: 1.2, disfunción TAPSE 10mm • ECOdoppler: VFS-P: ocupación de luz sin no-compresibilidad bilateral

18. Caso 3 Tratamiento • Angiografía pulmonar> trombectomía (PAm33>32); no trombolisis • HNF (bolo 80 U/kg >perfusión 18 U/kg/h>ajustada a TTPa 1.5-2.5) • A los 2 días tinzaparina 175 U/kg qd • A los 5 días inicio warfarina • A los 20 días stop tinzaparina (INR 2.02)

19. Pregunta caso 3 • ¿Cuanto tiempo anticoagularías a este paciente? • 3 meses • 6 meses • 1 año • Indefinido

20. Lo que qué dicen las guías • 5.2.1. In patients with a high clinical suspicion of acute PE, we suggest treatment with parenteral anticoagulants compared with no treatment while awaiting the results of diagnostic tests (Grade 2C). • 5.4.1. In patients with acute PE, we suggest LMWH or fondaparinux over IV UFH (Grade 2C for LMWH; Grade 2B for fondaparinux) and over SC UFH (Grade 2B for LMWH; Grade 2C for fondaparinux) . Remarks:Local considerations such as cost, availability, and familiarity of use dictate the choice between fondaparinux and LMWH. LMWH and fondaparinux are retained in patients with renal impairment, whereas this is not a concern with UFH. In patients with PE where there is concern about the adequacy of SC absorption or in patients in whom thrombolytic therapy is being considered or planned, initial treatment with IV UFH is preferred to use of SC therapies. • 5.5. In patients with low-risk PE and whose home circumstances are adequate, we suggest early discharge over standard discharge (eg, after first 5 days of treatment) (Grade 2B) .

21. Criterios de Wells. • Síntomas clínicos de TVP 3,0 • Otros diagnósticos menos probables 3,0 • Frecuencia cardiaca mayor de 100 l.p.m. 1,5 • Inmovilización o cirugía en las últimas 4 semanas 1,5 • Antecedentes de TVP o TEP 1,5 • Hemoptisis 1,0 • Cáncer 1,0 Probabilidad Clínica de TEP. • Baja < 2 • Intermedia 2-6 • Alta > 6 Wells PS y cols. Ann Intern Med 2001.

22. Escala de riesgo pronóstico: PESI simplificado • Edad > 80 años 1 punto • Historia de cáncer 1 punto • Historia de insuficiencia cardiaca o EPOC 1 punto • Pulso > 110 lpm 1 punto • Presión arterial sistólica < 100 mmHg 1 punto • Saturación de O2 < 90% 1 punto Recomendación: • Bajo riesgo: 0 puntos Alta precoz / hospitalización domiciliaria • Alto riesgo: >1 Ingreso hospitalario. • Elevación de Troponina y/o disfunción de VD (ecocardiograma): valorar UCI Jimenez D et al. Chest 2007

23. Lo que dicen las guías • 5.6.1.1. In patients with acute PE associated with hypotension (eg, systolic BP , 90 mm Hg) who do not have a high bleeding risk, we suggest systemically administered thrombolytic therapy over no such therapy (Grade 2C). • 5.6.1.2. In most patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy (Grade 1C). • 5.6.1.3. In selected patients with acute PE not associated with hypotension and with a low bleeding risk whose initial clinical presentation, or clinical course after starting anticoagulant therapy, suggests a high risk of developing hypotension, we suggest administration of thrombolytic therapy (Grade 2C). • 5.7. In patients with acute PE associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention (Grade 2C). • 6.3.1. In patients with a first VTE that is an unprovoked PE and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B).

24. Caso 4 • Varón de 45 años, HTA, fumador, sin antecedentes familiares de TEV • Desde hace 4 semanas dolor centrotorácico sin vegetatismo y dísnea progresiva>actualmente de reposo • Hipotenso, mal perfundido, FC:125 lpm. • SpO2 95% (Mónagan), PAO2/FIO2 145 (n>300),DD 2152 ng/mL, troponina I 0.20 ug/L; ECG: S1Q3T3 • ECOcar TT: dilatación + disfunción VD • AngioTAC: TEP masivo bilateral, sobrecarga cav. D, área vidrio deslustrado base , posible TVP. • ECOdoppler: TVP FP MII • OD: TEP + Neumonía

25. Caso 4 • Arteriografía>trombectomía + fibrinolisis local Puente de la Constitución Vacaciones de Navidad

26. Lo que dicen las guías • 5.6.2.1. In patients with acute PE, when a thrombolytic agent is used, we suggest short infusion times (eg, a 2-h infusion) over prolonged infusion times (eg, a 24-h infusion) (Grade 2C). • 5.6.2.2. In patients with acute PE when a thrombolytic agent is used, we suggest administration through a peripheral vein over a pulmonary artery catheter (Grade 2C) . • 5.9.1. In patients with acute PE who are treated with anticoagulants, we recommend against the use of an IVC filter (Grade 1B) .

27. Caso 5 • Varón 84 años, HTA, DLP, DM-II, BNCO, Cardiopatía isquémica (IAM hace años), I. renal crónica (creat 140), dependiente, movilización muy limitada • AAS, pravastatina, insulina, haloperidol, omeprazol, O2 domiciliario • Historia de 4 días de febrícula, expectoración purulenta, dísnea • TA: 130/60, FC: 81, • Sat O2: 98, DD6500, Troponina T <0.03 μg/L (n<0.014) • TAC con contraste: TEP ramas segmento ant. LSD, condensación LID • ECOcar: FE 45% hipocinesia septal • HBPM>acenocumarol

28. Pregunta caso 5 • ¿Cuanto tiempo anticoagularías a este paciente? • 3 meses • 6 meses • 1 año • Indefinido

29. Lo que dicen las guías • 6.3.2. In patients with a first VTE that is an unprovoked PE and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (Grade 1B) .

30. Factores de riesgo de hemorragia en el tratamiento del TEV con AVK (9ª ed guía ACCP) Puntuación

32. Caso 6 • Mujer 74 años, HTA, DM, DLP, TVP MII post-histerectomía hace 20 años > acenocumarol 4 años, antecedentes en familiares 1er orden de TEV • Dianben, Omeprazol • Acude por dolor y aumento del perímetro de MII • MII caliente, empastamiento gemelar, asimetría • DD 1200 • ECOdoppler: TVP IFP MII

33. Lo que dicen las guías • 3.1.4.4. In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (Grade 1B), and we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Grade 2B) . • 3.1.4.5. In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (Grade 2B) .

34. Caso 7 • Varón de 72 años • Cáncer ductal infiltrante de mama, metástasis óseas, estadio IV (6/11) • TEP bilateral incidental (7/11) durante tto tamoxifeno/zometa >tinzaparina 175 UI/kg qd 6 meses>AVK • Progresión M1 óseas y progresión biológica > decapeptyl/letrozol/zometa

35. Lo que dicen las guías • 6.4. In patients with PE and active cancer, if there is a low or moderate bleeding risk, we recommend extended anticoagulant therapy over 3 months of therapy (Grade 1B) , and if there is a high bleeding risk, we suggest extended anticoagulant therapy (Grade 2B) . Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually). • 6.7. In patients with PE and cancer, we suggest LMWH over VKA therapy (Grade 2B) . In patients with PE and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy (Grade 2C). • 6.9. In patients who are incidentally found to have asymptomatic PE, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic PE (Grade 2B).

36. El Montanyà, Seva 2013 X Curso de Formación Continuada Muchas gracias