In a patient with acute chest pain and moderate/low pre‑test probability for pulmonary embolism or aortic dissection, why should a D‑dimer be ordered, and why must NSAIDs be avoided during evaluation for possible acute coronary syndrome (including the mechanism of increased cardiac risk)?

Why Check D-dimer in Acute Chest Pain

In patients with acute chest pain and moderate/low pre-test probability, D-dimer must be checked to safely rule out life-threatening conditions—specifically pulmonary embolism and acute aortic dissection—both of which have sensitivities of 94-100% at the standard 0.5 μg/mL cutoff. 1, 2

D-dimer as a Rule-Out Test for Life-Threatening Conditions

Pulmonary Embolism

• For patients with low or intermediate clinical probability of PE, obtain a high-sensitivity D-dimer measurement as the initial diagnostic test rather than proceeding directly to imaging 1
• A negative D-dimer (<0.5 μg/mL or age-adjusted cutoff) combined with low/intermediate pretest probability safely excludes PE with a negative predictive value of 99-100%, allowing the 3-month thromboembolic risk to remain <1% without anticoagulation 1
• Use age-adjusted D-dimer thresholds (age × 10 ng/mL) in patients older than 50 years to improve specificity from 34% to 46% while maintaining >97% sensitivity 1
• Never obtain D-dimer in high pretest probability patients—proceed directly to CT pulmonary angiography 1

Acute Aortic Dissection

• D-dimer >0.5 μg/mL demonstrates 94-100% sensitivity for acute aortic dissection when measured within 24 hours of symptom onset, with a negative likelihood ratio of 0.07 1, 2
• The median D-dimer in acute aortic dissection is 4.9 μg/mL (compared to 0.6 μg/mL in other chest pain causes), making it markedly elevated 3, 4
• A negative D-dimer (<0.5 μg/mL) has a negative predictive value of 96.6-100% for ruling out aortic dissection 1, 4

Critical Limitations to Recognize

• D-dimer may be falsely negative in 5-9% of aortic dissections, particularly with intramural hematoma, thrombosed false lumen, or penetrating aortic ulcer 1, 3
• D-dimer has high sensitivity but low specificity (35-73%), meaning a positive result requires confirmatory imaging and cannot diagnose disease 1, 4
• D-dimer is frequently elevated in non-thrombotic conditions including cancer, sepsis, recent surgery/trauma, pregnancy, advanced age, and inflammatory states 1, 5, 6

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Why NSAIDs Must Be Avoided in Suspected ACS

NSAIDs increase the risk of major adverse cardiac events through multiple mechanisms: they promote thrombosis by inhibiting prostacyclin (a natural antiplatelet and vasodilator), increase blood pressure and fluid retention, and may mask ischemic symptoms, all of which worsen outcomes in acute coronary syndrome.

Prothrombotic Mechanisms

COX-2 Inhibition and Prostacyclin Suppression

• NSAIDs selectively inhibit COX-2 in vascular endothelium, reducing prostacyclin (PGI2) production—a critical endogenous antiplatelet agent and vasodilator
• This creates a prothrombotic state by allowing unopposed thromboxane A2 activity from platelets (which promotes platelet aggregation and vasoconstriction)
• The imbalance between thromboxane A2 (prothrombotic) and prostacyclin (antithrombotic) shifts hemostasis toward clot formation

Endothelial Dysfunction

• NSAIDs impair endothelial-dependent vasodilation by reducing nitric oxide bioavailability
• This endothelial dysfunction promotes vasoconstriction in coronary arteries, potentially worsening myocardial ischemia

Hemodynamic Mechanisms

Blood Pressure Elevation

• NSAIDs cause sodium and water retention by inhibiting renal prostaglandin synthesis
• This increases blood pressure by 3-5 mmHg on average, increasing myocardial oxygen demand
• In patients with borderline coronary perfusion, even modest BP increases can precipitate ischemia

Reduced Coronary Perfusion

• Vasoconstriction from prostacyclin inhibition directly reduces coronary blood flow
• Combined with increased myocardial oxygen demand from elevated BP, this creates a supply-demand mismatch

Clinical Masking of Symptoms

• NSAIDs' analgesic and anti-inflammatory effects may mask chest pain or discomfort that would otherwise prompt earlier medical evaluation
• This delays diagnosis and treatment of evolving myocardial infarction, worsening outcomes

Evidence of Increased Cardiac Risk

• Multiple studies demonstrate NSAIDs increase risk of myocardial infarction, heart failure hospitalization, and cardiovascular death
• Risk is present even with short-term use (7-14 days) and increases with higher doses
• Both non-selective NSAIDs (ibuprofen, naproxen) and selective COX-2 inhibitors (celecoxib) carry cardiovascular risk, though the magnitude varies

The combination of prothrombotic effects, hemodynamic stress, and symptom masking makes NSAIDs particularly dangerous in the acute chest pain setting where ACS cannot be excluded.