Pneumologie Longembolie

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Thomas van der Linden
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1 Pneumologie 2012 Longembolie Prof M. Delcroix

2 PE diagnosis Reach a diagnostic certainty Identify patients who can be safely left untreated (use of algorythm) Management/outcome studies 3 months follow up rationale: recurrence rate of untreated VTE is about 50% recurrence rate of negative gold-standard (angiography) is 2% Cost-effectiveness analysis

3 Diagnostisch algoritme Klinische probabiliteit Laag of intermediair Hoog Elisa D-dimer Duplex OLM* 500 µg/l geen R/ > 500 µg/l Duplex OLM* Geen DVT Spiraal CT DVT R/ Geen DVT Spiraal CT DVT R/ Geen PE V/Q - angio LE R/ Geen LE geen R/ LE R/ Geen LE geen R/ LE R/ * niet vereist als multidetector CT R/ staat voor therapie

4 Clinical probability of PE assessed empirically rated low, intermediate, high or new validated scores (Geneva and Wells) low - 10% PE intermediate - 30 % PE high - 70 % PE PIOPED, very reproducible between centers

7 D-dimer and VTE Test Patients (PE/DVT) Sn Sp (n) (n) (%, 95% CI) (%, 95% CI) Classical ELISA* / (96-98) 39 (37-41) Vidas-DD* / (97-100) 40 (36-42) Classical latex / (83-89) 68 (64-72) LIA-test /0 100 (98-100) 40 (36-44) SimpliRED* / (86-94) 72 (70-74) *validated in outcome studies

8 A

9 Venous US VTE is one single disease PE caused by a DVT in 90 % of the cases residual DVT found in 70 % of the patients with confirmed PE

11 Risicostratificatie echo CG Troponine BNP D-dimer ontslag thrombolyse 11

12 Therapie voor LE ACCP guidelines 2012 LMWH (2C)/fondaparinux (2B) als eerste keus Niet bij ernstige nierinsufficiëntie Bij hoge klinische probabiliteit, onmiddellijk (2C) Minstens 5 dagen en tot INR therapeutisch voor 2 opeenvolgende dagen (1B) Oad > bid toediening (enkel met dubbele dosis, 2C) Bij kanker, ook lang termijn (2B) 12

13 Malignancy Recurrence rate of 21 % during the first year 1-2 Lee, CLOT, NEJM 2003 Dalteparine vs warfarine 200 U/kg od for 1 mo, 75% of the full dose for the next 5 mo n = 676, 6 months Recurrence rate 9 vs 17 % 1 Prandoni 2002; 2 Hutten 2000

14 Dose reduction of LMWH? Severe renal impairment (Ccl<30ml/min) for Clexane and Fraxiparine not for Innohep Obesity not for Clexane and Innohep Elderly not for Clexane and Innohep

15 Dosing in pregnancy Risk stratification High: AT deficiency, antiphospholipid syndrome Moderate: homozygous factor V Leiden mutation, protein C/S deficiency, previous idiopathic VTE Low: heterozygous factor V Leiden mutation, previous post-traumatic traumatic uncomplicated VTE Treatment 3 months discontinued for labour and restarted 4h after delivery for 6 weeks Prophylaxis High: therapeutic dose (anti-xa IU/ml) Moderate and low: prophylactic dose (anti-xa IU/ml) from 16 weeks gestation Monitoring after 1 week and at 28 and 36 weeks gestation

16 Matisse-PE study multicenter, randomized, open-label including patients with acute symptomatic PE (n = 2213) comparing fondaparinux 7.5 mg SC oad with adjusted-dose dose IV UFH wo BW adaptation between 50 and 100 kg end points: symptomatic recurrent VTE and major bleeding (at 3 months) As effective and as safe

17 Therapie voor LE ACCP guidelines 2012 Coumarines opstarten dag 1 (2C) warfarin 10 mg first 2 days (2C) aanpassen dagelijks in functie van INR 2-3 (1B) INR 2-3 ook bij antifosfolipid syndroom (2B) 3 maanden bij transitoir risicofactor (1B) > > 3 maanden voor idiopatische LE (1B) 1 ste VTE en laag tot matig bloedingrisico (2B) 2 de VTE en laag (1B) of matig (2B) bloedingrisico Herevaluatie elk jaar 17

18 Therapie voor LE ACCP guidelines 2012 Coumarines Aanhoudend stabiel INR, volgende bepaling na 12w (2B) INR of 3-3.5, 3.5, control na 1-2 weken (2C) INR zonder bloeding, geen Vit K (2B) INR > 10 zonder bloeding, wel Vit K (2C) Bij bloeding, FFP (2C) en Vit K 5-10 mg traag IV (2C) Bij competente patiënten, patient self-management strategy (Coagucheck, 2B) Dosing decision support tools (2C) Concomitant gebruik van NSAID (graad 2C), en anti- aggregantia (graad 2C) vermijden 18

19 Warfarin dosing algorithm Kim, J Thromb Haemost 2009 Improves TTR from 67 to 73%

20 Tailored duration of LT anticoagulation? Determinants catch-up phenomenon VKA 1 % per year 6-12 mo after discontinuation 5-10% x2 with cancer /2 with major transient risk factor subsequent years 2 % per year risk factors estimated individual risk for recurrent VTE risk of bleeding Age, previous stroke, peptic ulcer, gastrointestinal bleeding, renal impairment, liver disease, diabetes mellitus, anemia, thrombocytopenia, antiplatelet therapy patient preferences 20

21 Risk factors for VTE Normal population 1/1000/year Low risk (OR 6): 12 months (Grade C) Age > y OR 3 Second generation pill OR 2 Third generation pill OR 5? Hyperhomocysteinemia OR 2-3 Anticardiolipin antibodies OR 2-3 Increased factor VIII OR 5-6 Heterozygous prothrombin mutation OR 3-5 Heterozygous factor V Leiden mutation OR 6-9 Intermediate risk (10 > OR > 6): years (Grade C) Pregnancy OR 10 Lupus anticoagulans OR 8-10 Heterozygous Protein C/S deficiencies OR 5-10 (20?) High risk (OR > 10): indefinite (Grade C) Heterozygous AT deficiency OR (70?) Homozygous factor V Leiden mutation OR Homozygous Protein C/S deficiencies OR >100

22 Risk of recurrent VTE Cumulative rate of recurrence 25% at 5 years and 30% at 10 years Associated condition HR 95% CI Ref Surgery Prandoni, Ann Intern Med 1996 Recent trauma or fracture Molecular thrombophilia Cancer Idiopathic VTE Christiansen, JAMA 2005 Unprovoked VTE Prandoni, Haematologica 2007 Factor V Leiden Ho, Arch Intern Med 2006 Prothrombine G20210A Male gender Kyrle, NEJM 2004 Male gender McRae, Lancet 2006

23 Criteria consistently associated with increased risk of recurrence Male gender Unprovoked character of the event Increased D-dimers 1 month after discontinuation Bounameaux and Perrier, Hematology 2008

24 7 studies N=1888 patients who completed at least 3 months of anticoagulation for a first episode of unprovoked VTE D-dimers measured 3 to 6 weeks after treatment Negative 3.5% annual risk for recurrent disease Positive 8.9% annual risk for recurrence

25 Residual thrombosis to predict recurrence Prandoni et al, Ann Intern Med 2002 Normal CUS 39% at 6 mo 58% at 1 y 69% at 2 y 74% at 3 y Persistent thrombosis (HR 2.4)

26 Risk of bleeding Major bleeding 3% per year 10% fatal ICB 0.3% Age-dependent

27 Bleeding scores AF VTE Gage et al, Am Heart J 2006 Ruiz-Gimenez et al, Thromb Haemost 2008

28 Combination of AAS, clopidogrel and VKA (AMI) Sorensen et al, Lancet 2009

29 Two-step algorithm Agnelli and Becattini, J Thromb Thrombolysis 2008; 25: 37

30 Schulman and Ogren, Thromb Haemost 2006

31 AAS 42% event reduction Becattini et al, NEJM 2012; 366: 1959

32 Therapie voor LE ACCP guidelines 2012 Thrombolyse Bij hypotensie en klinische verslechtering (2C) 2 uur infuus (2C) ESC guidelines

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