Simplified approach to investigation of suspected VTE

Transcription

1 Simplified approach to investigation of suspected VTE Diagnosis of DVT and PE THSNA 2016, Chicago 15 April 2016 Clive Kearon, McMaster University, Canada

2 Relevant Disclosures Research Support/P.I. Employee Consultant Major Stockholder Speakers Bureau Honoraria Scientific Advisory Board Canadian Institutes Health Research Heart & Stroke Foundation of Ontario National Institutes of Health Bayer Inc. No relevant Bayer Inc. No relevant No relevant No relevant No relevant

3 Outline Goals of diagnostic testing Ruling-in & Rule-out VTE Clinical evaluation as a diagnostic test D-dimer (with clinical evaluation) Imaging tests for DVT and PE Diagnostic combinations Difficult diagnostic situations

4 Goal of Diagnostic Testing for DVT & PE Who needs treatment have VTE & Anticoagulants will do more good than harm Who doesn t need treatment don t have VTE OR VTE but anticoags more harm than good (will resolve and won t recur without Rx) Need to narrow differential diagnosis

5 Ruling-in and Ruling-out a Diagnosis What level of certainty is acceptable?

6 Ruling-in and Ruling-out a Diagnosis What level of certainty is acceptable? Ruling-in (to treat) Depends on toxicity of treatment - high certainty if toxic Ruling-out (not to treat) Depends on consequences of missed diagnosis - high certainty if:(i) rapidly fatal and (ii) effective treatment

7 Ruling-in DVT or PE Probability of PE ³85% Anticoagulants are toxic (~4% bleeding 3 m) Ruling-out DVT or PE Probability recurrent VTE 2% Recurrent PE may be fatal Anticoagulants are very effective (~ 80% RR)

8 100% 85% VTE Diagnosed 50% 2% 0% VTE Excluded management

9 100% 85% PTP prevalence VTE Diagnosed 50% ~25% 2% 0% VTE Excluded management

10 First diagnostic assessment

11 Clinical Assessment of DVT & PE Signs and symptoms Risk factor for VTE Alternative diagnosis as likely

12 Alternative diagnosis as likely -2 Active cancer 1 Paralysis, paresis or plaster cast 1 Bedridden > 3 days (1 month) 1 Tenderness of deep veins 1 Entire leg swollen 1 Calf swelling (3 cm > other leg) 1 Pitting edema 1 Dilated superficial veins 1 History of VTE 1 Total points Clinical Assessment: Low: < 1; Moderate: 1-2; High > 2 for first or recurrent DVT Wells, J Intern Med 1998 Geersing BMJ 2014

13 No other more likely diagnosis 3 Signs & Symptoms of DVT (tender/swelling) 3 Active cancer 1 Previous DVT or PE 1.5 Immobilization / Surgery <4 weeks 1.5 Heart rate > 100/min 1.5 Hemoptysis 1 Total points Clinical Assessment: Low or Unlikely: < 4.5 for PE Wells, Thromb Haemost 2000 Moderate: 4.5-6; High: > 6

14 Wells Model for DVT & PE Clinical Suspicion Prevalence VTE High Moderate Low (15% of patients) (35% of patients) (50% of patients) 75% 25% <10%

15 Wells Model for DVT & PE Clinical Suspicion High Moderate Low Prevalence VTE 75% 25% <10% Likelihood Ratio ~8 ~1 ~0.3

16 100% 85% PTP Clinical PTP VTE Diagnosed High 50% Moderate Low 2% 0% VTE Excluded management

17 D-dimer

18 Cross-linked fibrin Plasmin D-dimer

19 Almost always increased with acute VTE (sensitive test) Increased by other conditions and age (non-specific test)

20 D-dimer Very sensitive: very high NPV, rarely negative ( 95%) ( 98%) (~30%) e.g. D-dimer <500 ug FEU/L Mod sensitive: lower NPV, often negative (~90%) (~95%) (~60%) e.g. SimpliRED +ive or ive

21 100% 85% 50% ~25% PTP prevalence Very Sensitive D-dimer Positive VTE Diagnosed High C-PTP rarely negative lower NPV not worth doing 2% 0% Negative VTE Excluded management

22 100% 85% PTP prevalence Moderately Sensitive D-dimer Mod Sen D-dimer + PTP 50% ~25% 2% 0% Negative Negative + Low PTP

23 To get more negative D-dimers

24 To get more negative D-dimers Increase D-dimer threshold (higher specificity & lower sensitivity) Two ways proposed

25 Age-adjusted D-dimer threshold Theory: Because D-dimer increases with age, can use higher threshold in elderly 50 years Threshold 500ug/L >50 years Threshold = age x 10 ug/l e.g. 78 years x 10 = 780ug/L

26 Age-adjusted D-dimer threshold Supported by: Many retrospective analyses for DVT and PE One prospective cohort of suspected PE Non-high C-PTP & D-dimer 500 to Age x 10 Prevalence: 337/3346 (10.1%) VTE at 3 mo: 1/331 (0.3%, 95%CI ) Righini for ADJUST-PE JAMA 2014

27 C-PTP-adjusted D-dimer threshold Theory: Because less VTE with low C-PTP, can exclude VTE with much higher D-dimer Low C-PTP Threshold 1,000ug/L Moderate C-PTP Threshold 500ug/L 2-fold difference

28 C-PTP-adjusted D-dimer threshold Supported by: Some retrospective analyses for DVT and PE One randomized trial in suspected DVT Low C-PTP CPTP & D-dimer 500 to 999 Prevalence in outpatients: 169/1422 (11.9%) VTE at 3 mo: 0/169 (0%, 95%CI ) RCT comparison: -0.3% (95%CI -1.8 to 0.8) Linkins for SELECT Ann Intern Med 2013

29 D-dimer not worth doing if: Very unlikely to get a negative result very high C-PTP another reason for a positive test Low NPV will not change management very high C-PTP Eg: After surgery; cancer; sepsis

30 Okay! When you can t rule out DVT or PE with Clinical PTP & D-dimer?

31 Diagnostic Imaging for DVT

32 Compression Ultrasonography (CUS) Imaging Test of Choice for DVT

33 US probe US probe No compression Compression

34 Common Femoral Proximal US Whole leg US Calf v. Trifurcation

35 Proximal US Common Femoral Calf v. Trifurcation easy accurate DVT important often diagnostic with C-PTP or D-d alone, does not exclude all DVT may require 2 nd US after 1 week

36 Whole leg US Common Femoral Calf v. Trifurcation (with distal veins) more complex less accurate DVT of uncertain importance excludes all DVT Distal US may be an unhelpful additional test

37 Diagnostic for First DVT US of proximal veins Venography (ascending, CT, MRI) Excludes DVT (including recurrent) Two of: Low C-PTP Negative D-dimer (moderate sensitivity) Negative proximal CUS (or no new vs. pervious) Negative proximal CUS on Day 1 and 7 (serial US) Negative ultrasound of all deep veins Negative D-dimer (very sensitive + non-high C-PTP) Venography of all deep veins

38 Recurrent DVT: additional criteria (thrombus can persist indefinitely) Diagnostic for Recurrent DVT New DVT on proximal US compared to previous (new CFV, Pop, Tri; 4 mm diam; 10 cm longer) Venography (ascending, CT, direct thrombus imaging MRI) Excludes recurrent DVT No new DVT on serial testing (Day 7, Day 14) No acute findings on venography (ascend, CT, MRI)

39 Diagnostic Imaging for PE

40 CT Pulmonary Angiography (CTPA)

41 No PE on CTPA ( & good quality study [~95%]) Multidetector CT, 12 studies; 2982 patients VTE 3 mo follow-up: 1.1% (95% CI ) Carrier J Thromb Haemost 2010

42 Positive Predictive Value of CT by Anatomical Level & Clinical Assessment Clinical Suspicion High Intermed. Low All Main / lobar 96% 99% 89% 97% Segmental 100% 79% 64% 68% Sub-seg. none ~33% ~20% 25%

43 Positive Predictive Value of CT by Anatomical Level & Clinical Assessment Clinical Suspicion High Intermed. Low All Main / lobar 96% 99% 89% 97% Segmental 100% 79% 64% 68% Sub-seg. none ~33% ~20% 25%

44 Ventilation-Perfusion Scanning

45 Ventilation-Perfusion Scanning Often preferred to CTPA Renal impairment Contrast dye allergy Younger (esp. females <40 yr) Pregnancy

46 Ventilation/Perfusion Scan and Clinical Assessment Normal perfusion ~25% Hi-prob & mod/high PTP ~10% Other combinations ~65% (overall prevalence of PE ~20%) PE - + +

47 SPECT V/Q scanning (single-photon emission CT) 3 D ventilation and perfusion imaging better resolution of defects than 2D planar non-diagnostic reduced from ~60% to 5% the general impression is that SPECT is better than planar Stein J Nucl Med 2009; SNM practice Guidelines J Nucl Med 2012

48 SPECT V/Q scanning BUT, NO: Large, prospective, multicentre studies WITH Blind comparison with a criterion standard OR Follow-up after withholding anticoagulation with No PE interpretation

49 Non-diagnostic combinations DVT Hx VTE, abnormal US, D-dimer +ive (Serial US; may treat) Small abnormality on US, D-dimer +ive (Serial US; may treat) PE Non-diagnostic CTPA (technical, small ILFD, Hx VTE) & no DVT & D-dimer +ive (Serial US; 2 nd CTPA) SPECT non-diagnostic V/Q (no CTPA; renal failure) & no DVT & D-dimer +ive (Serial US;?CTPA)

50 Conclusions There is no right way to diagnose DVT & PE (many effective strategies) C-PTP and D-dimer can often exclude DVT/PE Can t always reach a definitive diagnosis Can manage safely when can t reach a definitive diagnosis (often serial tests for DVT)