1. Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis in cancer patients Thrombosis Research (2008) 123, 177–183 혈액종양내과 R1 김현수

2. Introduction Patients with malignancy high risk of developing venous thrombosis the treatment of thrombosis with anticoagulants - risk of bleeding Clinical prediction models history and physical examination to categorize a patient's probability of having a disease The Wells pretest probability (PTP) model for diagnosing DVT in symptomatic patient

3. Introduction PTP model low, moderate, or high likelihood likely or unlikely risk group combination with D-dimer safely manage patients with suspected DVT. The negative predictive value of low or unlikely PTP and a negative D-dimer result, ranges from 99.1% to 99. 6% It is safe to withhold anticoagulant Tx negative D-dimer and either a low or unlikely PTP at initial presentation

4. Introduction patients with cancer is less certain.  The studies that validated PTP models did include cancer patients but the scoring does not take into account the strong risk factors for DVT that are unique to cancer patients.  while some studies showed that D-dimer testing had comparable negative predictive values in patients with cancer compared to patients without cancer, others have not.  the high prevalence of DVT in cancer patients may sufficiently reduce the negative predictive value of these diagnostic tools and render them less useful

5. Introduction Introduction 3 large prospective cohort studies  compare the performance of the Wells PTP model and D-dimer testing between patients with and without cancer  examine the utility of the two PTP model classification schemes (low/moderate/ high versus unlikely/likely) in excluding DVT in patients with cancer.

6. methods the databases from three prospective diagnostic studies in consecutive outpatients with suspected DVT that were performed at 7 Canadian tertiary care centers between 1997 and 2002 with symptoms of DVT at either the emergency departments or the thromboembolism clinics

7. methods patients with a low or unlikely PTP score and a negative D-dimer result and had no further testing, were not treated with anticoagulants and were followed for 3 months to detect thrombotic events. Compression ultrasonography and/ or venography of the symptomatic leg were performed in all patients who had a high or likely PTP score or a positive D-dimer result.

8. methods DVT was considered present if any of the following  any segment of non-compressibility of the common femoral vein to the trifurcation of the popliteal vein on compression ultrasonography  intra-luminal filling defect of any leg vein on contrast venography  objectively confirmed venous TE during the 3- month f/u period

9. methods

10. Results

11. Results

12. Results

13. Results Overall, 22% of patients without cancer had a low PTP and a negative D-dimer result and 36% had an unlikely PTP and a negative D-dimer result. In patients with cancer, only 6% and 12% of patients had a low or unlikely PTP and a negative D-dimer result, respectively

14. Discussion The clinical utility of D-dimer testing is limited in cancer patients  low or unlikely PTP with D-dimer(-) in cancer Pts - high negative predictive values  because D-dimer levels are often elevated in cancer patients in the absence of DVT, the D-dimer test has low specificity in both low and unlikely PTP categories The unlikely/likely PTP stratification more clinically useful because it has higher specificity and negative predictive value than the low PTP category when combined with a negative D-dimer result.

15. Discussion the specificity of the D-dimer test was quite low in cancer patients.

16. Discussion 6% cancer Pts - low PTP and negative D-dimer 94% - further testing after PTP modeling and D-dimer testing 88%- unlikely need further investigations. not exclude DVT in most patients with cancer, despite the high negative predictive value cost-effective avoid D-dimer testing in cancer patients and proceed with other diagnostic studies

17. Discussion A recent cost effectiveness analysis D-dimers are cost-effective with suspected PE suggesting that the cost-sparing effect of D-dimer is maintained until the proportion of patient with D-dimer negative and low and intermediate PTP is above 12.5%. In our study 6% and 12% of cancer patients had a low or unlikely PTP and a negative D-dimer result, respectively suggesting that a diagnostic strategy using D-dimer might not be cost effective. However, prospective studies are required to confirm these findings.

18. Limitation First, three different D-dimer assays with different operating characteristics were used. Second, we did not have any objective confirmation of the patients' active cancer diagnosis Finally, the total number of cancer patients from the 3 studies was small, leading to wide confidence intervals for our accuracy indices estimates.

19. conclusion D-dimer testing is not useful in cancer patients and these patients should directly proceed to have diagnostic imaging.