D-dimer in the Diagnosis of Pulmonary Embolism Cheryl Pollock PGY-3

Clinical Case 27 y.o. male 27 y.o. male Right anterior chest pain x 48h Right anterior chest pain x 48h Pleuritic; constant ache Pleuritic; constant ache Mild non-productive cough, no hemoptysis Mild non-productive cough, no hemoptysis Dyspnea on exertion Dyspnea on exertion No h/o trauma No h/o trauma

Physical Exam Vitals: Vitals:  HR 76reg RR 18 T 37 BP 130/76 CVS: CVS:  HS normal S1S2, no S3S4. No murmur.  No leg swelling. Resp: Resp:  Normal breath sound intensity.  Fine crackles R base.

Diagnostic Testing Goal is to allow the clinician to revise the patient’s probability of having disease to a level greater than a treatment threshold or less than a test threshold Goal is to allow the clinician to revise the patient’s probability of having disease to a level greater than a treatment threshold or less than a test threshold

Diagnostic Testing The cost of missing pulmonary embolism (PE) is high The cost of missing pulmonary embolism (PE) is high ED evaluation of patients with suspected PE is often complex, time-consuming ED evaluation of patients with suspected PE is often complex, time-consuming D-dimer is increasingly used in the evaluation of suspected PE D-dimer is increasingly used in the evaluation of suspected PE

Do you want a D-dimer? Definition Definition Conditions that cause a positive D-dimer Conditions that cause a positive D-dimer Assays Assays Its role in the work-up of pulmonary embolus Its role in the work-up of pulmonary embolus –Wells criteria –Diagnostic algorithm

D-dimer Defined Fibrin degradation product (FDP) Fibrin degradation product (FDP) Plasmin splits fibrin into fibrinogen and FDPs Plasmin splits fibrin into fibrinogen and FDPs Fibrinolysis starts within 1h of thrombus formation Fibrinolysis starts within 1h of thrombus formation T 1/2 D-dimers = 4-6 h T 1/2 D-dimers = 4-6 h Continued PE fibrinolysis = elevated D- dimer levels for at least one week Continued PE fibrinolysis = elevated D- dimer levels for at least one week

Positive D-dimer Venous thromboembolism Venous thromboembolism DIC DIC Acute coronary syndromes Acute coronary syndromes Vasculitis Vasculitis Malignancies: lung, prostate, cervix, colon Malignancies: lung, prostate, cervix, colon Vaso-occlusive sickle cell crisis Vaso-occlusive sickle cell crisis Acute cerebrovascular accident Acute cerebrovascular accident Critically ill with severe infection, trauma, inflammatory disorders Critically ill with severe infection, trauma, inflammatory disorders

Positive D-dimer Many of these conditions are themselves risk factors for venous thromboembolism Many of these conditions are themselves risk factors for venous thromboembolism This complicates the interpretation of an abnormal value This complicates the interpretation of an abnormal value

D-dimer Assays Five major types available: Five major types available: –Enzyme-linked immunosorbent assay (ELISA)  Rapid ELISA –Latex agglutination assay –Whole blood assay –Turbidimetric assay –Immunofiltration assay

ELISA Assay Positive if > 500ng/ml Positive if > 500ng/ml In the diagnosis of PE: In the diagnosis of PE: –Sensitivity= 94-97% –Specificity= 44% –Negative LR = 0.07 Drawback: 2-4h to perform Drawback: 2-4h to perform Rapid ELISA Rapid ELISA –< 2h –Similar sensitivity and negative LR

Interpretation of Results Estimation of the pretest probability is imperative for proper application of results Estimation of the pretest probability is imperative for proper application of results Various methods: Various methods: –Wells et al (Canada) –Wicki et al (Switzerland) –Kline et al (USA) The Wells criteria is used in this facility The Wells criteria is used in this facility

Wells Criteria Criteria Points Points Suspected DVT Alternative Dx less likely Heart rate >100 bpm Immobilization/surgery Previous DVT/PE Hemoptysis Malignancy

Wells Criteria: Risk Interpretation Score Probability of PE, % % with this score Risk 0-2 points Low Low 3-6 points Moderate Moderate >6 points High High

Low Probability D-dimer Negative STOP Positive V/Q Scan Normal STOP High Pulm Angio Positive TREAT Normal STOP Non-high US Legs DVT TREAT Normal US 1 week

Moderate Probability D-dimer Negative STOP Positive V/Q scan Non-High US legs Normal US in 1 week Pulm angio DVT TREAT High TREAT Normal

High Probability V/Q scan Normal US legs DVT TREAT Normal Pulm angio US 1week Pulm angio Non-High Pulm angio High TREAT

Summary A normal D-dimer by an ELISA assay can safely exclude PE in patients with LOW to MODERATE pretest probability A normal D-dimer by an ELISA assay can safely exclude PE in patients with LOW to MODERATE pretest probability HIGH pretest probability V/Q scan HIGH pretest probability V/Q scan D-dimer can’t “rule in” PE D-dimer can’t “rule in” PE In elderly or inpatients D-dimer usually abnormal- not useful In elderly or inpatients D-dimer usually abnormal- not useful

Clinical Case Wells score Wells 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 probability Low pretest probability D-dimer = negative D-dimer = negative

The Simplest Algorithm You can safely rule out PE in pretest LOW-probablilty patients with a negative D-dimer You can safely rule out PE in pretest LOW-probablilty patients with a negative D-dimer

Hampton’s Hump

High Probability VQ Scan

EKG Findings