Does Rheumatoid Arthritis (RA) increase the risk of developing Pulmonary Embolisms (PEs)?

Does Rheumatoid Arthritis Increase the Risk of Pulmonary Embolism?

Yes, rheumatoid arthritis significantly increases the risk of pulmonary embolism, with patients facing approximately 2-3 times the risk compared to the general population.

Magnitude of Risk

The evidence consistently demonstrates elevated PE risk in RA patients across multiple high-quality studies:

• RA patients have a 2.15-fold increased risk of pulmonary embolism compared to age and sex-matched healthy controls, based on a comprehensive meta-analysis of 272,884 RA patients 1
• The risk ratio for PE is 2.23 (95% CI 1.75-2.86) in a UK population-based study of 9,589 RA patients, with an incidence rate of 1.5 per 1,000 person-years 2
• The adjusted hazard ratio for venous thromboembolism remains 1.4-1.5 even after controlling for traditional VTE risk factors including cardiovascular disease, surgery, hospitalization, and medications 3

Time-Dependent Risk Pattern

The risk of PE in RA patients varies significantly by disease duration:

• The highest risk occurs within the first year after RA diagnosis, with a relative risk of 3.27 for PE 2
• Risk remains persistently elevated at 1-5 years (RR 1.88) and beyond 5 years (RR 2.35) 2
• This pattern holds true even in outpatient populations, where 84.5% of patients had no recent hospitalization 2

Pathophysiological Mechanisms

The increased PE risk in RA stems from multiple interconnected mechanisms:

• Chronic systemic inflammation activates all three components of Virchow's triad: vascular injury, hypercoagulation, and venous stasis 4, 5
• Elevated inflammatory markers including C-reactive protein, interleukin-6, and tumor necrosis factor-α contribute to a prothrombotic state 6, 4
• Endothelial dysfunction from chronic inflammation promotes thrombus formation 5
• Antiphospholipid antibodies and hyperhomocysteinemia are more prevalent in RA patients and contribute to thrombotic tendency 4

Clinical Risk Factors Specific to RA

Beyond traditional VTE risk factors, RA patients face additional disease-specific risks:

• Uncontrolled disease activity requiring switching of biologic DMARDs increases VTE incidence 4
• Rheumatoid factor seropositivity confers higher risk (hazard ratio 2.59) compared to seronegative patients 6
• Major orthopedic surgery, particularly knee or hip replacement (common in RA), represents a strong provoked risk factor 7
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib) carry additional VTE risk requiring careful consideration 6, 4
• Corticosteroid use may increase VTE risk, while methotrexate and other conventional DMARDs may reduce it 6

Critical Clinical Implications

Maintain heightened clinical suspicion for PE in RA patients, particularly during high-risk periods:

• First year after RA diagnosis represents the highest risk window 2
• Perioperative period for major orthopedic surgery requires aggressive thromboprophylaxis 7
• Hospitalization for acute illness with immobilization mandates VTE prophylaxis 4
• Initiation or switching of certain DMARDs, especially JAK inhibitors, warrants increased monitoring 6, 4

Common Pitfalls to Avoid

• Do not dismiss PE symptoms as RA-related dyspnea or chest pain from pleuritis or pericarditis, as cardiac involvement occurs in only 7.6% of RA patients 6
• Do not assume traditional VTE risk stratification tools adequately capture RA-specific risk, as one-third of RA patients who develop VTE have at least one major risk factor within 90 days of the event 3
• Do not overlook that the elevated risk persists even after adjusting for traditional VTE risk factors, indicating RA itself is an independent risk factor 3, 2
• Recognize that autoimmune diseases are classified as moderate risk factors for provoked PE by the European Society of Cardiology 7

Monitoring Recommendations

Implement systematic VTE risk assessment in RA patients, particularly:

• During periods of high disease activity requiring treatment escalation 4
• Before and after major surgery, with extended thromboprophylaxis for 2-3 months post-operatively 7
• When prescribing JAK inhibitors, given their documented association with increased VTE risk 6
• In patients with multiple concurrent risk factors, as these have additive effects 7