Prospective evaluation of Innovance D-dimer in the exclusion of venous thromboembolism [VTE].

1. Prospective evaluation of Innovance D-dimer in the exclusion of venous thromboembolism [VTE]. Robert Gosselin, CLS Department of Clinical Pathology and Laboratory Medicine University of California, Davis Health System Sacramento, CA

2. D-dimer • Indicates clot formation • Indicates clot degradation • D-dimer test commonly used for exclusion: • Pulmonary embolism • Deep vein thrombosis • Consumptive coagulopathy • Aortic dissection

3. Innovance D-dimer and Stratus CS D-dimer new test from Siemen Healthcare • Prospective study in the US to validate cut-off for excluding PE and DVT

4. 3 sites in US • Duke University • Cleveland Clinic • UC Davis • Total enrollment all sites • 550 PE • 480 DVT

5. Inclusion criteria • First clinically suspected PE and/or DVT • Objective testing • Diagnostic algorithms • Radiographic studies • Capable of giving informed consent • Agree to 3 month follow-up for patients with negative imaging studies.

6. Exclusion criteria • Under 18 years of age • Pregnant • Previous Hx of PE or DVT • Resolved symptoms >72 hours before presenting to ED • Oral anticoagulation • 3 month f/u not available • Inpatient • Prisoners

7. Clinical Probability for DVT Active cancer +1 Paralysis, paresis, recent casting of leg +1 Bedridden (>3 days) or major (>12 weeks) +1 Entire leg swollen +1 Calf swelling (>3cm) compared to other leg +1 Pitting edema greater in symptomatic leg +1 Collateral nonvaricose superficial veins +1 Localized tenderness along deep venous system +1 Previously documented DVT +1 Alternative Dx as or more likely than DVT -2 Score: DVT unlikely <2 DVT likely >2 Wells PS, et al Lancet 1997; 350:1795-98; N Engl J Med 2003;349: 1227-35

8. Clinical Probability for PE Clinical signs and symptoms of DVT +3 Heart rate >100/min +1.5 Hemoptysis +1 Active cancer +1 Bedridden (>3 days) or major (>12 weeks) +1.5 Previously history of DVT or PE +1.5 PE most likely diagnosis +3 Score: Low <2 Moderate 2-6 High >6 Wells PS, et al Thromb Haemost 2000; 83:416-20.

9. DVT Algorithm Compression US Positive Negative Low prob Serial CUS (5-8 days) Mod or High Prob Positive Negative 3 month f/u Positive VTE Negative VTE DVT Positive DVT Negative

10. PE Algorithm Spiral CT or Angiogram Positive Negative 3 month f/u Positive VTE Negative VTE PE Positive PE Negative

11. After informed consent • Blood collected • 3.2% sodium citrate • Lithium heparin (Stratus only) • If testing within 4 hours of collection • Whole blood heparin on Stratus • Plasma testing on other analyzers • If testing not completed within 4 hours of collection • Samples processed and refrigerated • Testing completed within 24 hours of collection

12. Testing performed on: Sysmex analyzers CA560 CA1500 CA7000 BCS Stratus (heparin and citrate testing) [Delayed testing---CS2000i]

13. As of May 11, 2009 • 381 patients enrolled • 353 with demographics complete • 284 with 3 mo f/u • 2 withdrawn • One patient declined participation after testing completed [1 month later] • One patient had imaging studies canceled after enrollment • 4 pending 3 month f/u • 8 patients expired • 0/8 with normal D-dimer levels

14. 37% males [91/248] Median age 51.5 years [range 19-81 years] Patients with PE studies • Probability scores • Low probability 62% [154/248] • Moderate probability 33% [82/248] • High probability 3% [7/248] • No score performed 2% [5/248] Patients with DVT studies • Probability scores • Unlikely 64.4% [94/146] • Likely 30.8% [45/146] • No score performed 4.7% [7/146]

15. Of the 353 patients with demographics: • 70.2% [248/353] tested for PE • 238 with spiral CT • 12 with V/Q scan • 25 with PE [10.5%] • 41.4% [146/353] CUS for DVT • 13 with DVT [9.6%] 37 patients evaluated for PE and DVT • 30 with CT and CUS • 6 with VQ and CUS • 1 with CUS, CT and VQ • 3 patients with both DVT and PE

16. 3.7 Innovance D-dimer mg/L 0.8 No VTE VTE

17. PE Probability DVT Probability Innovance D-dimer, mg/L Low Mod High Unlikely Likely

18. Data for all patients enrolled SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

19. Innovance D-dimer in all VTE SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

20. Patients evaluated for PE N=248 SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

21. Innovance D-dimer in PE SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

22. Patients evaluated for DVT N=146 SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

23. Innovance D-dimer in DVT SCS-H Heparin sample on Stratus SCS-C Citrate sample on Stratus

24. Summary • Poor positive predictive value of D-dimer with VTE • Acceptable negative predictive value for Innovance D-dimer in excluding VTE in outpatients • Need more data for PE sensitivity • Weakness • Few positive samples in subset analysis

25. Fellow collaborators at UC Davis • Edward Panacek, MD, MPH • Abhi Gorhi, MS, CCRP • Shari Nichols, CCRP • Allyson Sage, RN • Leslie Freeman, CLS • Andrea Picazo, CCRP