WGA meeting Management and follow-up VTE in clinical pratice Dr Borgoens CHR Citadelle Liège

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1 WGA meeting 2016 Management and follow-up VTE in clinical pratice Dr Borgoens CHR Citadelle Liège

2 Clinical question Which complementary investigations are you going to plan during or early after hospitalization after diagnosis of pulmonary embolism? 1 Thrombophilia screening 2 Cancer screening 3 Echocardiography 4 CT Angiography 5 Lung V/P scintigraphy

3 Clinical question Which complementary investigations are you goingto plane duringor earlyafter hospitalization after diagnosis of pulmonary embolism? 1 Thrombophilia screening 2 Cancer screening 3 Echocardiography 4 CT Angiography 5 Lung V/P scintigraphy USELESS TO REPEAT IF DIAGNOSIS CONFIRMED

4 Thrombophiliascreening in VTE disease?

5 Thrombophilia screening, timing? Factor V Leiden (APCR), factor II mutation, antibody (APL) titers can be performed at any time PC, PS influenced by: acute phase, pregnancy, estrogen, VKA (2months) AT UFH -> Perform testing 2-4 weeks following period off anticoagulation, no pregnancy, no estrogen

6 Thrombophilia: pro contra

7 PRO? From international angiology vol 32 n 2 April 2013

8 PRO?

9 CONTRA significant

10 Thrombophilia screening Age at first episode VTE Unprovoked >< provoked Family history 1st VTE< 40y Estrogen therapy or pregnancy as the only risk factor <60y unprovoked VTE except significant triggering factor Recurrent VTE Recurrent superficial vein thrombosis in the absence varicose veins VTE unusual sites <50y Warfarin induced skin necrosis or neonates purpura fulminans not related to sepsis Asymptomatic (female in childbearing age) with 1st degree proven symptomatic thrombophilia Patients should be advised and followed up by a specialist hematologist From international angiology vol 32 n 2 April 2013

11 Cancer screening? YES 10% patients unprovoked PE ->cancer, especially 1-2y after PE 854 pts Symptomatic unprovoked proximal DVT or PE Limited cancer screening: Basic blood testing, chest Xray, screening for breast> 50y, cervical 18-70y, prostate cancer >40y (psa) Limited cancer screening+ abdo pelvis CT (virtual colonoscopy gastroscopy included) No clinical benefit with abdo pelvis CT

12 Echocardiographyend of hospitalization? No recommendation No toxicity and can help to assess indirectly favorable evolution if massive or submassive PE

13 Clinical question How do youorganizethe followup of VTE disease? 1 GP 1st week and every month 2 Specialist 1st month and every 3 months 3 GP 1st week and every month + specialist 3 months later 4 GP 1st week and every month + specialist 1 month later

14 Clinical question But no clear recommendations How 3 monthsisthe do youorganizethe minimal followup duration for of VTE VTE disease? (provoked><unprovoked) 1 GP: ensureoac 1st week and adherence, every months clinicalevolution, 2 Specialist 1st month cancer and screening every 3 months 3 GP 1st week and every month + specialist 3 months later 4 GP 1st week and every month + specialist 1 month later

15 Clinical question How do youorganizethe followup for PE at 3 months? Echocardiography? 1: Yes 2: No

16 Echocardiography FOLLOW UP: Detection of chronic thromboembolic pulmonary hypertension CTEPH (incidence 0,1-9,1% 2Y post PE) Routine screening CTEPH after PE not systematically recommended but clinical symptoms and signs are non specific or absent in early CTEPH

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18 Clinical question How do youorganizethe followup for PE at 3-6 months? Lung V/P scintigraphy? 1: Yes 2: No

19 Interest of lung scintigraphy for follow up PE: Resolution perfusion defect 6 months post PE ->depends on initial extension of perfusion defect ->impact to PE recurrence (47 m f up) ->small studies no recommendation

20 Clinical question How do youorganizethe followup for PE at 3-6 months? CT ANGIOGRAPHY? 1: Yes 2: No

21 Interest CT pulmonary angiography for follow up PE Thromb Haemost Jul;114(1): doi: /TH Epub 2015 May 28. Thromboembolic resolution assessed by CT pulmonary angiography after treatment for acute pulmonary embolism. den Exter PL 1, van Es J, Kroft LJ, Erkens PM, Douma RA, Mos IC, Jonkers G, Hovens MM, Durian MF, ten Cate H, Beenen LF, Kamphuisen PW, Huisman MV; Prometheus Follow-Up Investigators. Prospective, multi-center cohort study, 157 patients with acute PE diagnosed by CT pulmonary angiography CTPA-imaging after six months of anticoagulant treatment to assess residual thromboembolic obstruction Follow up 2,5y -> complete PE resolution at 6 m: 84% -> VTE recurrence: 10,2% -> residual obstruction not associated with VTE recurrence : HR 0,92 -> no routine use CTPA for PE follow up

22 Clinical question How do youorganizethe followup for DVT at 3-6 months? LegCUS DOPPLER? 1: Yes 2: No

23 OR 1,5 for all DVT (significant) but OR 1,2 for unprovoked DVT (ns)

24 Thromb Haemost Jan;111(1): Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis: a patient-level meta-analysis. Donadini MP 1, Ageno W, Antonucci E, Cosmi B, Kovacs MJ, Le Gal G, Ockelford P, Poli D, Prandoni P, Rodger M, Saccullo G, Siragusa S, Young L, Bonzini M, Caprioli M, Dentali F, Iorio A, Douketis JD. RVO was independently associated with recurrent VTE (HR = 1.32) ( ). Associa-on if RVO was detected 3 months a0er DVT (HR = 2.17) ( ), but non-significant if detected later, i.e. >6 months (HR = 1.19) ( ).

25 CUS 3 monthspost DVT Residual venous thrombosis 4mm Commun femoral or poplitea 869 patients 49% RVT 3months Risk similar unprovoked and provoked -> global events -> Recurrent VTE -> PTS -> cancer -> Arterial thrombotic disorders Screening global high risk patients? HR 2,51

26 538 patients Fixedduration: 3m (provoked) or 6 m (unprovoked) HR 0,64 (0,39-0,99) Flexible duration: CUS 3 and 9m (provoked) or to 21m (unprovoked) If no residualthrombus ->stop OAT If residual thrombus -> OAT

27 Residualvenousthrombosison CUS to guide duration of anticoagulation? ->No clearevidence, canhelp 3 months>6months 538 patients But HR 0,64 (0,39-0,99) Fixedduration: 3m provoked or 6 m unprovoked Flexible duration: CUS 3 and 9m provoked or to 21m unprovoked Interestto performcus at the end of treatment If no residualthrombus ->stop OAT If residual thrombus -> OAT >REFERENCE EXAM for followup

28 Clinical question How do youorganizethe followup for VTE disease at 3 months? D-dimer? 1: Yes 2: No

29 Thromb Haemost May;105(5): doi: /TH Epub 2011 Feb 28. D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis. Cosmi B 1, Legnani C, Cini M, Guazzaloca G, Palareti G. Provoked DVT Ddimere D0 D+30 after anticoagulation withdrawal D-dimer D 0 :HR 4,2 for recurrence VTE D-dimer D 30 : HR 3,8 for recurrence VTE Residual vein obstruction not associated with recurrence

30 1st unprovoked VTE (608 patients) AVK at least 3months D-dimer 1month post-vka discontinuation If abnormal D-dimer-> randomisation To resume or discontinue VKA HR 2,27 (1,15-4,47) for VTE recurrence if D-dimer positive/normal without anticoagulation

31 Patients with normal D-d T3 months->13months: risk of recurrence Patients with abnormal D-d T3months and 13months: risk of recurrence

32 First unprovoked or associated weak risk factors VTE DVT recanalized or stable (1010 patients) Serial D-dimer measurements: D 0 undervka 3m or 12m(RVO) -> If negative->d 15,D 30,D 60,D 90 Negative: (528 patients) -> stop anticoagulation Positive: (482 patients) -> resume anticoagulation But 109 refuse anticoagulation

33 419 patients PE and DVT 1st unprovoked After 3-7m therapy ->Ddimer D0 and D30 Stop OAC if D-dimer negative or Restart OAC if D-dimer positive D-dimer testing negative: isnot enoughto stop OAC in Men withunprovokedvte but can help for women, especially when VTE under estrogen therapy

34 D-dimer measurements: 419 patients PE and DVT 1st unprovoked After 3-7m therapy D 0 (VKA), D +30 (withoutvka) or or serial ->Ddimer D0 measurements>d and D30 30 (without VKA) Stop OAC if Ddimer negative or Restart OAC if Ddimer positive ->helpfulto guide duration of anticoagulation, especially for D women dimer testing negative: isnot enoughto stop OAC in Men withunprovokedvte but can help for women, especially when VTE under estrogen therapy 2

35 Slide 36 2 for Muriel Sprynger; 9/04/2016

36 Clinical question How do youorganizethe followup for VTE disease at 3 months? Do you use recurrence VTE prediction models and/or bleeding risk model? 1: Yes 2: No

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38 Patients with PE recur more frequently with a PE Mortality of PE 2-3x higher than DVT

39 Prediction scores for recurrence of VTE

40 Abnormal Ddimer (1month): +2points Age<50y: +1point Sex, male: +1point Hormone associated VTE: -2 points DASH SCORE 1 LOW RISK: stop anticoagulation? DASH SCORE >1 HIGH RISK: continuation anticoagulation?

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43 HER D OO model for womenunprovokedvte HER under VKA D O O If 2 high risk recurrence for women Male -> high risk

44 Predictionscores for bleeding, OAC (VKA) in VTE disease

45 BLEEDING RISK VTE (1st 3month warfarin anticoagulation)

46 Bleeding risk VTE (ACCP guidelines 2016)