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

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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

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

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• 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

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

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• 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.

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• Exclusion criteria
• Under 18 years of age
• Pregnant
• Previous Hx of PE or DVT
• Resolved symptoms gt72 hours before presenting to
  ED
• Oral anticoagulation
• 3 month f/u not available
• Inpatient
• Prisoners

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Clinical Probability for DVT

• Active cancer 1
• Paralysis, paresis, recent casting of leg 1
• Bedridden (gt3 days) or major (gt12 weeks) 1
• Entire leg swollen 1
• Calf swelling (gt3cm) 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 lt2 DVT likely gt2

Wells PS, et al Lancet 1997 3501795-98 N Engl
J Med 2003349 1227-35
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Clinical Probability for PE

• Clinical signs and symptoms of DVT 3
• Heart rate gt100/min 1.5
• Hemoptysis 1
• Active cancer 1
• Bedridden (gt3 days) or major (gt12 weeks) 1.5
• Previously history of DVT or PE 1.5
• PE most likely diagnosis 3

Score Low lt2 Moderate 2-6 High gt6
Wells PS, et al Thromb Haemost 2000 83416-20.
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DVT Algorithm
Compression US
Positive
Negative
Low prob
Serial CUS (5-8 days)
Mod or High Prob
3 month f/u
Positive
Negative
Positive VTE
Negative VTE
DVT Positive
DVT Negative
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PE Algorithm
Spiral CT or Angiogram
Positive
Negative
3 month f/u
Positive VTE
Negative VTE
PE Positive
PE Negative
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• 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

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Testing performed on Sysmex analyzers CA560
CA1500 CA7000 BCS Stratus (heparin and
citrate testing) Delayed testing---CS2000i
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• 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

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• 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

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• 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

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3.7
Innovance D-dimer mg/L
0.8
No VTE
VTE
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PE Probability
DVT Probability
Innovance D-dimer, mg/L
Low
Mod
High
Unlikely
Likely
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Data for all patients enrolled
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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Innovance D-dimer in all VTE
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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Patients evaluated for PE N248
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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Innovance D-dimer in PE
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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Patients evaluated for DVT N146
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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Innovance D-dimer in DVT
SCS-H Heparin sample on Stratus SCS-C Citrate
sample on Stratus
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• 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

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• 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