Medical Disclaimer
  • For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
  • Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
  • Accuracy Not Guaranteed: While all content has been prepared to the best of my knowledge and ability, errors or omissions may exist.
  • Verify Before Acting: Users are responsible for verifying information through authoritative sources before any clinical application.
AI Assistance Notice
The clinical content and references are curated and reviewed by myself; however, AI was used to assist in organizing, paraphrasing, and formatting the information presented.
Quick Reference
  • Normal Range: <500 ng/mL (FEU) or <250 ng/mL (DDU) - assay-dependent
  • Age-Adjusted Cutoff: Age × 10 ng/mL for patients >50 years (improves specificity)
  • Negative Predictive Value: >95% for VTE (negative D-dimer effectively rules out DVT/PE in low-risk patients)
  • Positive Predictive Value: Poor (~30%) - many non-thrombotic conditions elevate D-dimer
  • Primary Use: RULE OUT VTE (DVT/PE) when combined with clinical probability assessment (Wells score, PERC rule)
  • Sample Type: Citrated plasma (blue-top tube)
  • Key Point: "D-dimer rules OUT, not IN" - high sensitivity but low specificity means negative test excludes VTE, but positive test requires imaging

Test Description

What is D-dimer?

D-dimer is a fibrin degradation product (FDP) produced when cross-linked fibrin in blood clots is broken down by plasmin during fibrinolysis. The presence of elevated D-dimer indicates that significant clot formation AND breakdown has recently occurred in the body.

How is D-dimer Formed?

D-dimer formation requires several sequential steps in coagulation and fibrinolysis:

  • Step 1 - Fibrin formation: Thrombin cleaves fibrinogen → fibrin monomers → spontaneous polymerization into fibrin strands
  • Step 2 - Cross-linking: Factor XIIIa (activated by thrombin) cross-links adjacent fibrin molecules creating stable D-D bonds
  • Step 3 - Fibrinolysis: Plasmin (activated from plasminogen) degrades cross-linked fibrin mesh
  • Step 4 - D-dimer release: Plasmin cleaves specific D-D cross-linked fibrin fragments → releases D-dimer into circulation

D-dimer vs Other Fibrin Degradation Products

D-dimer is SPECIFIC for cross-linked fibrin breakdown: Unlike other fibrin degradation products (FDPs) that can result from fibrinogen breakdown, D-dimer only forms from degradation of CROSS-LINKED fibrin. This means D-dimer indicates that a stable thrombus formed (with Factor XIII cross-linking) and was subsequently broken down by fibrinolysis. This makes D-dimer more specific for active thrombosis than general FDPs.

Why is D-dimer Useful for VTE Diagnosis?

D-dimer has exceptional characteristics for ruling out venous thromboembolism:

  • High sensitivity (95-98%): Nearly all patients with acute DVT or PE have elevated D-dimer
  • High negative predictive value (>95%): Negative D-dimer in low-risk patient essentially excludes VTE
  • Low specificity (~50%): Many non-thrombotic conditions elevate D-dimer (pregnancy, cancer, infection, surgery, trauma)
  • Clinical utility: Excellent "rule-out" test when combined with clinical probability assessment

Assay Types and Units

Different D-dimer assays use different units, causing confusion. Always check your laboratory's reference range and units.

  • FEU (Fibrinogen Equivalent Units): Most common in US; normal <500 ng/mL FEU
  • DDU (D-dimer Units): Used internationally; normal <250 ng/mL DDU
  • Conversion: 1 FEU = 2 DDU (approximately); 500 ng/mL FEU ≈ 250 ng/mL DDU
  • Assay methods: ELISA (most sensitive), latex agglutination (rapid but less sensitive), automated immunoassays
Clinical Significance

Elevated D-dimer - Thrombotic Causes

D-dimer elevation indicates recent clot formation and breakdown. Most clinically significant causes involve venous or arterial thrombosis.

Venous Thromboembolism (VTE) - Primary Indication

  • Deep Vein Thrombosis (DVT): Lower extremity, upper extremity, or unusual site thrombosis
  • Pulmonary Embolism (PE): D-dimer elevated in >95% of acute PE cases
  • Sensitivity: 95-98% for acute VTE (rarely miss VTE with negative D-dimer)
  • Timing: D-dimer rises within hours of thrombus formation, peaks at 1-2 days
  • Duration: Remains elevated for days to weeks even with anticoagulation (doesn't normalize immediately)

Disseminated Intravascular Coagulation (DIC)

  • Mechanism: Widespread microvascular thrombosis → massive fibrin formation and breakdown
  • D-dimer levels: Markedly elevated (often >4000-10,000 ng/mL)
  • DIC diagnosis: Elevated D-dimer + low fibrinogen + low platelets + prolonged PT/aPTT
  • Sensitivity: Nearly 100% of DIC patients have elevated D-dimer

Other Thrombotic Conditions

  • Aortic dissection: Intramural thrombus formation → D-dimer often >500 ng/mL (some studies suggest >1600 ng/mL has good sensitivity)
  • Myocardial infarction: Coronary thrombus → mild D-dimer elevation
  • Stroke (ischemic): Cerebral thrombus → variable D-dimer elevation
  • Peripheral arterial thrombosis: Acute limb ischemia from thrombus

Elevated D-dimer - Non-Thrombotic Causes

Many common conditions elevate D-dimer WITHOUT thrombosis, limiting specificity. This is why positive D-dimer requires imaging confirmation.

Pregnancy and Obstetric Conditions

  • Normal pregnancy: D-dimer physiologically increases each trimester (400 → 600 → 800-1200 ng/mL)
  • Preeclampsia/HELLP: Endothelial activation → elevated D-dimer
  • Placental abruption: Retroplacental hematoma → fibrin formation/breakdown
  • Clinical implication: D-dimer has limited utility for PE diagnosis in late pregnancy (use imaging)

Malignancy

  • Mechanism: Tumor-associated procoagulant activity + increased fibrinolysis
  • Solid tumors: Lung, breast, GI, prostate cancers elevate D-dimer
  • Hematologic malignancies: Leukemia, lymphoma
  • Metastatic disease: Higher D-dimer correlates with worse prognosis in some cancers

Infection and Inflammation

  • Sepsis: Systemic inflammation + microvascular thrombosis → elevated D-dimer
  • COVID-19: Hypercoagulable state; elevated D-dimer predicts severity and mortality
  • Pneumonia: Bacterial or viral pneumonia may elevate D-dimer
  • Inflammatory disorders: Rheumatoid arthritis, inflammatory bowel disease

Surgery and Trauma

  • Mechanism: Tissue injury → thrombin generation → fibrin formation
  • Post-operative: D-dimer elevated for 1-2 weeks after major surgery
  • Trauma: Proportional to injury severity
  • Burns: Extensive burns cause marked D-dimer elevation

Other Non-Thrombotic Causes

  • Advanced age: Baseline D-dimer increases with age (hence age-adjusted cutoffs)
  • Heart failure: Chronic heart failure often has mild D-dimer elevation
  • Atrial fibrillation: May have chronically elevated D-dimer
  • Chronic kidney disease: Impaired clearance
  • Liver disease: Variable; severe cirrhosis may have elevated D-dimer from DIC-like state
  • Sickle cell disease: Vaso-occlusive crises elevate D-dimer

Normal D-dimer (Below Cutoff)

A negative D-dimer in the appropriate clinical context effectively rules out acute VTE.

  • VTE exclusion: Negative D-dimer + low or intermediate Wells score → <1% probability of VTE (no imaging needed)
  • PERC rule: Negative D-dimer + negative PERC rule → PE extremely unlikely (<2% probability)
  • Important caveat: D-dimer only rules out ACUTE thrombosis; chronic DVT or old PE may have normal D-dimer
Interpretation Guidelines

Using D-dimer with Clinical Probability Scores

D-dimer should NEVER be ordered in isolation. Always combine with clinical probability assessment (Wells score or PERC rule).

Wells Score for DVT

Swipe to see more
Clinical Feature Points
Active cancer (treatment within 6 months or palliative) +1
Paralysis, paresis, or recent plaster immobilization of lower extremity +1
Recently bedridden >3 days or major surgery within 12 weeks +1
Localized tenderness along deep venous system +1
Entire leg swollen +1
Calf swelling >3 cm compared to asymptomatic leg +1
Pitting edema (greater in symptomatic leg) +1
Collateral superficial veins (non-varicose) +1
Alternative diagnosis at least as likely as DVT -2

Interpretation:

  • Score ≤0: Low probability (5% DVT risk) → D-dimer to rule out
  • Score 1-2: Moderate probability (17% DVT risk) → D-dimer to rule out
  • Score ≥3: High probability (53% DVT risk) → Skip D-dimer, get ultrasound

Wells Score for PE (Modified)

Swipe to see more
Clinical Feature Points
Clinical signs/symptoms of DVT +3
PE is #1 diagnosis OR equally likely +3
Heart rate >100 bpm +1.5
Immobilization ≥3 days OR surgery in previous 4 weeks +1.5
Previous DVT/PE +1.5
Hemoptysis +1
Malignancy (treatment within 6 months or palliative) +1

Interpretation:

  • Score <2: PE unlikely (12% risk) → D-dimer to rule out
  • Score 2-6: Moderate probability (30% risk) → D-dimer to rule out OR imaging
  • Score >6: PE likely (65% risk) → Skip D-dimer, get CTPA

PERC Rule (Pulmonary Embolism Rule-Out Criteria)

If ALL 8 criteria are met, PE prevalence <2% and D-dimer/imaging not needed:

  • Age <50 years
  • Heart rate <100 bpm
  • O2 saturation ≥95% on room air
  • No hemoptysis
  • No estrogen use
  • No prior DVT/PE
  • No unilateral leg swelling
  • No surgery/trauma requiring hospitalization within 4 weeks

Clinical use: If patient meets all 8 PERC criteria AND clinician gestalt estimates PE risk <15%, no further testing needed (including D-dimer).

D-dimer Diagnostic Algorithm for VTE

Step-by-Step Approach to Suspected DVT/PE:
  1. Assess clinical probability: Calculate Wells score OR apply PERC rule
  2. Low/Moderate probability:
    • Order D-dimer (age-adjusted if >50 years)
    • Negative D-dimer → VTE excluded, no imaging needed
    • Positive D-dimer → Proceed to imaging (ultrasound for DVT, CTPA for PE)
  3. High probability (Wells ≥3 for DVT or >6 for PE):
    • Skip D-dimer entirely
    • Proceed directly to imaging
    • Rationale: High pre-test probability means positive D-dimer not informative; negative D-dimer still requires imaging
  4. PERC-negative low-risk patient:
    • No D-dimer or imaging needed
    • Reassurance and discharge

When NOT to Order D-dimer

Do NOT order D-dimer in these situations:
  • High clinical probability: Wells score >6 for PE or ≥3 for DVT → Imaging regardless of D-dimer result
  • Already decided to image: If you're ordering CTPA or ultrasound anyway, D-dimer adds no value
  • Hemodynamically unstable PE: Massive PE with shock → immediate intervention, no time for D-dimer
  • Recent surgery (<2 weeks): D-dimer always elevated → false positive
  • Hospitalized patients: D-dimer often elevated from comorbidities → poor specificity
  • Pregnancy (3rd trimester): Nearly always elevated → use imaging
  • Known cancer: Often baseline elevated → low specificity
Interfering Factors

Physiologic Factors That Increase D-dimer

  • Age: D-dimer increases ~10 ng/mL per year after age 50 (hence age-adjusted cutoffs)
  • Pregnancy: Physiologic increase each trimester (normal in pregnancy ≠ normal in non-pregnant)
  • Female sex: Slightly higher baseline than males
  • African American race: May have slightly higher baseline D-dimer

Medical Conditions That Increase D-dimer

  • Infection/Sepsis: Inflammatory cytokines + microvascular thrombosis
  • Cancer: Nearly all malignancies elevate D-dimer to some degree
  • Trauma: Proportional to injury severity; elevated for days to weeks
  • Surgery: Remains elevated 1-2 weeks post-operatively
  • Heart failure: Chronic mild elevation
  • Atrial fibrillation: Chronic mild elevation
  • Renal failure: Decreased clearance
  • Liver disease: Variable; advanced cirrhosis may elevate D-dimer

Medications

  • Anticoagulants: Warfarin, heparin, DOACs do NOT normalize D-dimer immediately (thrombus still present initially)
  • Thrombolytics: tPA, streptokinase cause massive D-dimer elevation (massive fibrinolysis)
  • Estrogen/OCPs: May slightly increase baseline D-dimer

Pre-analytical Errors

  • Hemolyzed sample: May cause falsely elevated D-dimer (RBC lysis releases substances interfering with assay)
  • Lipemic sample: Turbidity interferes with immunoassay → falsely high
  • Rheumatoid factor: High RF may cause false positive in some assays
  • Underfilled tube: Excess citrate may affect results
  • Delayed processing: Should be tested within 4 hours; D-dimer stable longer than PT/aPTT

Assay Variability

  • Different assays have different cutoffs: ELISA (most sensitive), latex agglutination (less sensitive), automated immunoassays
  • FEU vs DDU units: 500 ng/mL FEU ≈ 250 ng/mL DDU (1:2 ratio)
  • Point-of-care assays: Rapid but less sensitive than lab-based ELISA; negative POC D-dimer may not be sufficient to rule out VTE
Clinical Pearls
Clinical Pearl
"D-dimer rules OUT, not IN": This mantra captures D-dimer's clinical utility perfectly. Negative D-dimer in low-risk patient excludes VTE with 95%+ certainty (excellent negative predictive value). But positive D-dimer only has ~30% positive predictive value - most elevated D-dimers are NOT from VTE. Always confirm positive D-dimer with imaging.
Clinical Pearl
Age-adjusted D-dimer is a game-changer: Using age × 10 ng/mL as cutoff for patients >50 increases specificity from 10% to 35% in elderly patients WITHOUT missing VTE. This prevents unnecessary CT scans in older adults who frequently have mildly elevated D-dimer from age/comorbidities. Always age-adjust D-dimer in patients >50 years.
Clinical Pearl
Don't order D-dimer if high probability: If Wells score ≥3 (DVT) or >6 (PE), proceed directly to imaging. Why? Even if D-dimer negative (rare in high-risk), you'd still image based on high clinical suspicion. And if D-dimer positive (expected), you still image. D-dimer adds no information in high-risk patients.
D-dimer loses utility in hospitalized patients: Inpatients have so many D-dimer-elevating comorbidities (infection, inflammation, immobility, surgery, cancer) that >60% have false positive D-dimers. Specificity plummets. In hospitalized patients with suspected VTE, consider proceeding directly to imaging rather than D-dimer.
PERC rule for ultra-low-risk PE: If patient meets all 8 PERC criteria (age <50, HR <100, O2 ≥95%, no hemoptysis, no estrogen, no prior VTE, no leg swelling, no recent surgery) AND your clinical gestalt says PE unlikely, you can skip D-dimer AND imaging entirely. PE risk <2% with PERC-negative. Don't over-test ultra-low-risk patients.
Clinical Pearl
D-dimer stays elevated even on anticoagulation: Starting heparin or warfarin does NOT immediately normalize D-dimer. The thrombus is still present (just not growing). D-dimer may take weeks to normalize. Don't repeat D-dimer to "monitor anticoagulation" - it's not useful. Use anti-Xa or INR instead.
Clinical Pearl
Markedly elevated D-dimer (>4000 ng/mL) suggests DIC: While D-dimer >500 ng/mL is "positive," very high levels (>4000-10,000 ng/mL) are more suggestive of DIC, massive thrombosis, or aortic dissection. Check platelets, fibrinogen, PT/aPTT to complete DIC workup.
D-dimer doesn't detect chronic DVT: D-dimer rules out ACUTE VTE (within days to weeks). Old, organized thrombus that's already been remodeled may have normal D-dimer. If suspecting chronic DVT or post-thrombotic syndrome, proceed directly to imaging - D-dimer won't help.
Clinical Pearl
COVID-19 and D-dimer: Elevated D-dimer in COVID-19 predicts disease severity, mortality, and thrombotic complications. D-dimer >1000 ng/mL in hospitalized COVID patient is high-risk marker. Some protocols use D-dimer to guide thromboprophylaxis intensity. But elevated D-dimer doesn't necessarily mean VTE - inflammation alone elevates it.
Pregnancy and D-dimer: D-dimer rises progressively during pregnancy (physiologic). By third trimester, nearly all pregnant women have D-dimer >500 ng/mL. D-dimer has limited utility for PE diagnosis in late pregnancy. If PE suspected in 3rd trimester, proceed to imaging (V/Q scan preferred to minimize fetal radiation). Negative D-dimer in 1st-2nd trimester can still rule out VTE.
References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/
Back to Coagulation Panel All Lab Values