D-dimer in the D-dimer in the Diagnosis of Diagnosis of
Pulmonary EmbolismPulmonary Embolism
Cheryl 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 The Wells criteria is used in this facilityfacility
Wells CriteriaWells Criteria
CriteriaCriteria PointsPoints
Suspected DVTSuspected DVT 3.0 3.0
Alternative Dx less Alternative Dx less likelylikely
3.0 3.0
Heart rate >100 bpmHeart rate >100 bpm 1.51.5
Immobilization/Immobilization/surgerysurgery
1.51.5
Previous DVT/PEPrevious DVT/PE 1.51.5
HemoptysisHemoptysis 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 Probability
D-dimer
Negative Positive
STOP V/Q scan
Non-HighHigh
Normal
TREATUS 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
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