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

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

Innovance D-dimer and Stratus CSInnovance 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 DVTProspective study in the US to validate cut-off for excluding PE and DVT

3 sites in US3 sites in US –Duke University –Cleveland Clinic –UC Davis Total enrollment all sitesTotal enrollment all sites –550 PE –480 DVT

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

Exclusion criteriaExclusion 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

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 Clinical Probability for DVT Wells PS, et al Lancet 1997; 350: ; N Engl J Med 2003;349:

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 Clinical Probability for PE Score:Low 6 Wells PS, et al Thromb Haemost 2000; 83:

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

Spiral CT or Angiogram PositiveNegative PE Positive Positive VTE PE Negative Negative VTE 3 month f/u PEAlgorithm

After informed consentAfter informed consent –Blood collected 3.2% sodium citrate3.2% sodium citrate Lithium heparin (Stratus only)Lithium heparin (Stratus only) –If testing within 4 hours of collection Whole blood heparin on StratusWhole blood heparin on Stratus Plasma testing on other analyzersPlasma testing on other analyzers –If testing not completed within 4 hours of collection Samples processed and refrigeratedSamples processed and refrigerated Testing completed within 24 hours of collectionTesting completed within 24 hours of collection

Testing performed on: Sysmex analyzers CA560CA1500CA7000BCS Stratus (heparin and citrate testing) [Delayed testing---CS2000i]

As of May 11, 2009As of May 11, 2009 –381 patients enrolled –353 with demographics complete –284 with 3 mo f/u 2 withdrawn2 withdrawn –One patient declined participation after testing completed [1 month later] –One patient had imaging studies canceled after enrollment 4 pending 3 month f/u4 pending 3 month f/u 8 patients expired8 patients expired –0/8 with normal D-dimer levels

37% males [91/248] Median age 51.5 years [range years] Patients with PE studies Probability scoresProbability 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 scoresProbability scores –Unlikely 64.4% [94/146] –Likely 30.8% [45/146] –No score performed 4.7% [7/146]

Of the 353 patients with demographics:Of the 353 patients with demographics: –70.2% [248/353] tested for PE 238 with spiral CT238 with spiral CT 12 with V/Q scan12 with V/Q scan 25 with PE [10.5%]25 with PE [10.5%] –41.4% [146/353] CUS for DVT 13 with DVT [9.6%]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

No VTE VTE Innovance D-dimer mg/L

Innovance D-dimer, mg/L LowModHighUnlikelyLikely PE Probability DVT Probability

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

Innovance D-dimer in all VTE

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

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

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

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

SummarySummary –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 analysisFew positive samples in subset analysis

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