Is sarcoidosis, particularly active disease or high‑dose steroid use, a risk factor for pulmonary embolism in adults?

Is Sarcoidosis a Risk Factor for Pulmonary Embolism?

Sarcoidosis itself is not formally recognized as an independent risk factor for pulmonary embolism in major international guidelines, but corticosteroid therapy used to treat sarcoidosis—particularly at doses ≥17.5 mg prednisone-equivalent daily—significantly increases PE risk and should be considered a modifiable risk factor.

Guideline-Based Risk Factors: What's Actually Listed

The most recent European Society of Cardiology/European Respiratory Society guidelines (2019) provide comprehensive lists of established PE risk factors, categorized by strength 1, 2, 3:

Strong risk factors (OR >10):

• Major trauma, lower limb fractures, hip/knee replacement 2
• Spinal cord injury 2
• Myocardial infarction within 3 months 2
• Previous VTE 2

Moderate risk factors (OR 2-9):

• Active cancer (especially pancreatic, hematological, lung, gastric, brain) 1, 2
• Infection (pneumonia, UTI, HIV) 1, 2
• Autoimmune diseases 2
• Central venous catheters 2

Weak risk factors (OR <2):

• Bed rest >3 days 2
• Obesity 2
• Diabetes mellitus 2

Notably, sarcoidosis is mentioned only in the 2004 ESC guidelines under "miscellaneous" causes of pulmonary hypertension—not as a PE risk factor 1.

The Corticosteroid Connection: The Real Culprit

The most robust evidence comes from a 2021 multivariate analysis of 649 patients that definitively clarified this relationship 4:

• Sarcoidosis itself (cardiac or extracardiac) was NOT an independent risk factor for VTE on multivariate regression (p >0.05) 4
• Corticosteroid use WAS independently associated with VTE: HR 3.06 for PE (p=0.007) and HR 6.21 for DVT (p<0.0001) 4
• Dose-dependent relationship: The optimal threshold for defining VTE risk was a prednisone-equivalent dose of 17.5 mg daily 4

This finding is corroborated by a 2016 nested case-control study showing current oral corticosteroid use increased recurrent PE risk (OR 3.74; 95% CI 2.04-6.87) 5.

Clinical Algorithm for PE Risk Assessment in Sarcoidosis Patients

When evaluating PE risk in a patient with sarcoidosis:

1. Assess corticosteroid exposure:

   • Current use of ≥17.5 mg prednisone-equivalent daily = HIGH RISK 4
   • Current use of <17.5 mg daily = MODERATE RISK 4
   • No corticosteroid use = assess other standard risk factors only 4

2. Screen for established PE risk factors per guidelines:

   • Recent surgery/trauma, immobilization, cancer, prior VTE 1, 2
   • Hormonal therapy (oral contraceptives, HRT) 1, 6
   • Active infection 1, 2

3. Consider thrombophilia testing only if:

   • PE occurs in young patients (<40 years) with minimal provocation 7, 8
   • Family history of VTE is present 7, 8
   • Recurrent VTE despite adequate anticoagulation 7, 8

Important Caveats and Pitfalls

The inflammation hypothesis remains unproven: While case reports suggest sarcoidosis-associated inflammation might promote hypercoagulability 9, 7, the largest controlled study found no independent association after adjusting for corticosteroid use 4. Do not attribute PE risk to "active sarcoidosis" without considering medication effects.

Avoid unnecessary thrombophilia workup: Case reports describe sarcoidosis patients with PE who also had Factor V Leiden or MTHFR mutations 7, 8, but these represent coincidental findings in patients with multiple risk factors—not evidence that sarcoidosis itself causes thrombosis.

D-dimer interpretation is problematic: Elevated D-dimers in sarcoidosis patients may reflect underlying inflammation rather than thrombosis 7. Use validated clinical decision rules (Wells score, Geneva score) rather than D-dimer alone when assessing PE probability 1.

Consider VTE prophylaxis for hospitalized patients: If a sarcoidosis patient requires hospitalization AND is receiving high-dose corticosteroids (≥17.5 mg prednisone-equivalent), implement pharmacological VTE prophylaxis per standard guidelines for medical patients 6.