D-dimer in the D-dimer in the Diagnosis of Diagnosis of

Pulmonary EmbolismPulmonary EmbolismCheryl Pollock PGY-3Cheryl Pollock PGY-3

Clinical CaseClinical Case 27 y.o. male27 y.o. male Right anterior chest pain x 48hRight anterior chest pain x 48h Pleuritic; constant achePleuritic; constant ache Mild non-productive cough, no Mild non-productive cough, no

hemoptysishemoptysis Dyspnea on exertionDyspnea on exertion No h/o traumaNo h/o trauma

Physical ExamPhysical Exam Vitals:Vitals:

HR 76reg RR 18 T 37 BP 130/76 HR 76reg RR 18 T 37 BP 130/76 CVS: CVS:

HS normal S1S2, no S3S4. No murmur. HS normal S1S2, no S3S4. No murmur. No leg swelling. No leg swelling.

Resp:Resp: Normal breath sound intensity. Normal breath sound intensity. Fine crackles R base.Fine crackles R base.

Diagnostic TestingDiagnostic Testing Goal is to allow the clinician to revise Goal is to allow the clinician to revise

the patient’s probability of having the patient’s probability of having disease to a level greater than a disease to a level greater than a treatment threshold or less than a treatment threshold or less than a test threshold test threshold

Diagnostic TestingDiagnostic Testing The cost of missing pulmonary The cost of missing pulmonary

embolism (PE) is highembolism (PE) is high ED evaluation of patients with ED evaluation of patients with

suspected PE is often complex, time-suspected PE is often complex, time-consumingconsuming

D-dimer is increasingly used in the D-dimer is increasingly used in the evaluation of suspected PEevaluation of suspected PE

Do you want a D-dimer?Do you want a D-dimer? DefinitionDefinition Conditions that cause a positive D-Conditions that cause a positive D-

dimerdimer AssaysAssays Its role in the work-up of pulmonary Its role in the work-up of pulmonary

embolusembolus– Wells criteriaWells criteria– Diagnostic algorithmDiagnostic algorithm

D-dimer DefinedD-dimer Defined Fibrin degradation product (FDP)Fibrin degradation product (FDP) Plasmin splits fibrin into fibrinogen Plasmin splits fibrin into fibrinogen

and FDPsand FDPs Fibrinolysis starts within 1h of Fibrinolysis starts within 1h of

thrombus formationthrombus formation TT1/21/2 D-dimers = 4-6 h D-dimers = 4-6 h Continued PE fibrinolysis = elevated Continued PE fibrinolysis = elevated

D-dimer levels for at least one weekD-dimer levels for at least one week

Positive D-dimer Positive D-dimer Venous thromboembolismVenous thromboembolism DICDIC Acute coronary syndromesAcute coronary syndromes VasculitisVasculitis Malignancies: lung, prostate, cervix, colonMalignancies: lung, prostate, cervix, colon Vaso-occlusive sickle cell crisisVaso-occlusive sickle cell crisis Acute cerebrovascular accidentAcute cerebrovascular accident Critically ill with severe infection, trauma, Critically ill with severe infection, trauma,

inflammatory disordersinflammatory disorders

Positive D-dimerPositive D-dimer Many of these conditions are Many of these conditions are

themselves risk factors for venous themselves risk factors for venous thromboembolismthromboembolism

This complicates the interpretation of This complicates the interpretation of an abnormal value an abnormal value

D-dimer Assays D-dimer Assays Five major types available:Five major types available:

– Enzyme-linked immunosorbent assay Enzyme-linked immunosorbent assay (ELISA)(ELISA) Rapid ELISARapid ELISA

– Latex agglutination assayLatex agglutination assay– Whole blood assayWhole blood assay– Turbidimetric assayTurbidimetric assay– Immunofiltration assayImmunofiltration assay

ELISA AssayELISA Assay Positive if > 500ng/mlPositive if > 500ng/ml In the diagnosis of PE:In the diagnosis of PE:

– Sensitivity= 94-97%Sensitivity= 94-97%– Specificity= 44%Specificity= 44%– Negative LR = 0.07Negative LR = 0.07

Drawback: 2-4h to performDrawback: 2-4h to perform Rapid ELISA Rapid ELISA

– < 2h< 2h– Similar sensitivity and negative LRSimilar sensitivity and negative LR

Interpretation of ResultsInterpretation of Results Estimation of the pretest probability is Estimation of the pretest probability is

imperative for proper application of imperative for proper application of resultsresults

Various methods:Various methods:– Wells et al (Canada)Wells et al (Canada)– Wicki et al (Switzerland)Wicki et al (Switzerland)– Kline et al (USA)Kline et al (USA)

The Wells criteria is used in this facilityThe Wells criteria is used in this facility

Wells CriteriaWells CriteriaCriteriaCriteria PointsPointsSuspected DVTSuspected DVT 3.0 3.0 Alternative Dx less Alternative Dx less likelylikely

3.0 3.0

Heart rate >100 bpmHeart rate >100 bpm 1.51.5Immobilization/Immobilization/surgerysurgery

1.51.5

Previous DVT/PEPrevious DVT/PE 1.51.5HemoptysisHemoptysis 1.0 1.0 MalignancyMalignancy 1.01.0

Wells Criteria: Risk Wells Criteria: Risk InterpretationInterpretation

ScoreScore ProbabilitProbability of PE, %y of PE, %

% with % with this this scorescore

RiskRisk

0-2 0-2 pointspoints

3.63.6 4040 LowLow

3-6 3-6 pointspoints

20.5 20.5 5353 ModerateModerate

>6 >6 pointspoints

66.766.7 77 HighHigh

Low Probability Low Probability D-dimer

Negative Positive

STOP V/Q Scan

Normal HighNon-high

STOPUS Legs Pulm Angio

DVTNormal

US 1 week TREAT

PositiveNormal

STOP TREAT

Moderate ProbabilityModerate ProbabilityD-dimer

Negative Positive

STOP V/Q scan

Non-HighHigh

NormalTREAT

US legs

Normal DVT

US in 1 weekPulm angio TREAT

High ProbabilityHigh Probability

V/Q scan

Normal Non-High High

TREATUS legs Pulm angioPulm angio

DVT Normal

TREAT Pulm angioUS 1week

SummarySummary A normal D-dimer by an ELISA assay A normal D-dimer by an ELISA assay

can safely exclude PE in patients with can safely exclude PE in patients with LOW to MODERATE pretest probabilityLOW to MODERATE pretest probability

HIGH pretest probability V/Q scanHIGH pretest probability V/Q scan D-dimer can’t “rule in” PED-dimer can’t “rule in” PE In elderly or inpatients D-dimer usually In elderly or inpatients D-dimer usually

abnormal- not useful abnormal- not useful

Clinical CaseClinical Case Wells scoreWells score

• No leg swelling, no painNo leg swelling, no pain• HR <100HR <100• No immobilizationNo immobilization• No prior DVT or PENo prior DVT or PE• No hemoptysisNo hemoptysis• No malignancyNo malignancy• CXR: RLL infiltrateCXR: RLL infiltrate

Low pretest probabilityLow pretest probability D-dimer = negativeD-dimer = negative

The Simplest AlgorithmThe Simplest Algorithm You can safely rule out PE in pretest You can safely rule out PE in pretest

LOW-probablilty patients with a LOW-probablilty patients with a negative D-dimernegative D-dimer

Hampton’s HumpHampton’s Hump

High Probability VQ ScanHigh Probability VQ Scan

EKG FindingsEKG Findings