Why Pulmonary Embolisms Cause Leukocytosis
Pulmonary embolisms trigger leukocytosis through an inflammatory response characterized by massive infiltrates of inflammatory cells in the right ventricular myocardium, driven by high levels of epinephrine released during PE-induced stress and neurohumoral activation. 1
Pathophysiological Mechanism
The inflammatory cascade in PE occurs through several interconnected pathways:
Neurohumoral activation results from both abnormal right ventricular wall tension and circulatory shock, triggering a systemic stress response that mobilizes white blood cells 1
PE-induced "myocarditis" develops from high levels of epinephrine released in response to acute right ventricular strain, leading to massive infiltrates of inflammatory cells in the RV myocardium of patients who die within 48 hours of acute PE 1, 2
Inflammatory cell infiltration in the right ventricular myocardium represents a direct tissue response to the acute hemodynamic stress and ischemic injury 1, 2
This inflammatory response may explain the secondary hemodynamic destabilization that sometimes occurs 24-48 hours after acute PE, though early PE recurrence remains an alternative explanation 1
Clinical Evidence and Magnitude
The actual degree of leukocytosis in PE is modest and clinically important to recognize:
Only 20% of PE patients without other causes of leukocytosis develop an elevated WBC count (>10,000/mm³) 3
No patients with isolated PE had WBC counts ≥20,000/mm³, distinguishing PE-related leukocytosis from infectious or other inflammatory causes 3
The presence or absence of pulmonary hemorrhage/infarction syndrome does not significantly affect the likelihood of leukocytosis (17% vs 24%, not statistically significant) 3
Clinical Implications and Pitfalls
Critical caveat: The presence of modest leukocytosis should not dissuade clinicians from pursuing objective diagnosis of PE 3. This is particularly important because:
PE frequently coexists with other conditions that themselves cause leukocytosis, making it difficult to attribute the elevated WBC count solely to the PE 3
The inflammatory response is part of the broader pathophysiological cascade involving right ventricular ischemia, myocyte damage, and systemic stress 1
Leukocytosis represents just one component of the systemic inflammatory response and should be interpreted in the full clinical context rather than as a diagnostic criterion 3
Underlying Mechanisms Beyond Inflammation
The leukocytosis also reflects broader pathophysiological derangements:
Right ventricular ischemia from imbalance between oxygen supply and demand causes cardiomyocyte damage and triggers inflammatory mediator release 1
Systemic vasoconstriction and compensatory mechanisms activate stress pathways that mobilize leukocytes from bone marrow and marginated pools 1
Tissue hypoxia in affected lung areas may contribute to local and systemic inflammatory responses 1
The key clinical takeaway is that while PE can cause leukocytosis through inflammatory mechanisms, the elevation is typically modest (WBC 10,000-20,000/mm³), and its presence or absence should not influence the decision to pursue definitive diagnostic testing for PE 3.