Does natural recirculation of blood into the bloodstream occur after thrombosis in pulmonary embolism (PE)?

Natural Blood Recirculation After Pulmonary Embolism

Natural recirculation of blood into the bloodstream does not occur after thrombosis in pulmonary embolism (PE); instead, resolution of pulmonary thrombi is frequently incomplete, with perfusion defects persisting in many patients even a year after the acute PE event. 1

Pathophysiology of Pulmonary Embolism

• Pulmonary embolism occurs when thromboemboli occlude pulmonary arteries, causing an abrupt increase in pulmonary vascular resistance (PVR) when >30-50% of the total cross-sectional area of the pulmonary arterial bed is blocked 1
• PE-induced vasoconstriction, mediated by thromboxane A2 and serotonin release, contributes to the initial increase in PVR 1
• The abrupt increase in PVR results in right ventricular (RV) dilation, altering contractile properties via the Frank-Starling mechanism 1
• This leads to increased RV pressure and wall tension, prolonged contraction time, and neurohumoral activation 1

Natural Course of Pulmonary Thrombi

• Following an acute PE episode, resolution of pulmonary thrombi is frequently incomplete 1
• Lung perfusion scintigraphy has demonstrated abnormalities in 35% of patients a year after acute PE, although the degree of pulmonary vascular obstruction was <15% in 90% of these cases 1
• Rather than natural recirculation, the body relies on its intrinsic fibrinolytic system to slowly break down clots over time, but this process is often incomplete 1

Long-Term Consequences of Incomplete Resolution

• In some patients, persistent perfusion defects can lead to chronic symptoms and functional limitations 1
• In a prospective observational study of 254 patients with PE, 29% had residual perfusion defects on lung scans after a median of 12 months 1
• Patients with residual perfusion defects were more often dyspneic (60% versus 36%) and had a shorter 6-minute walk distance (374 m versus 427 m) compared to those without defects 1
• Approximately 1.5% of patients with unprovoked PE develop chronic thromboembolic pulmonary hypertension (CTEPH), with most cases appearing within 24 months of the index event 1

Recurrence Risk After Pulmonary Embolism

• The risk of recurrent PE is highest during the first two weeks after the initial event and declines thereafter 1
• Based on historical data, the cumulative proportion of patients with early recurrence of VTE (while on anticoagulant treatment) is approximately 2.0% at 2 weeks, 6.4% at 3 months, and 8% at 6 months 1
• Late recurrence (after discontinuation of anticoagulation) reaches approximately 13% at 1 year, 23% at 5 years, and 30% at 10 years 1
• Recurrent VTE is likely to occur in the same clinical form as the index episode (i.e., if the first event was PE, recurrence will most likely be PE again) 1

Factors Affecting Thrombus Resolution

• The fibrinolytic system plays a crucial role in the natural resolution of thrombi, but its effectiveness varies among individuals 1, 2
• Prothrombotic fibrin clot phenotype (formation of more compact clots with impaired susceptibility to lysis) may predispose to recurrent PE 2
• Patients with recurrent PE have been found to have denser fibrin networks and impaired fibrinolysis compared to those without recurrence 2
• Independent predictors of recurrent PE include female sex, unprovoked venous thromboembolism, higher plasma D-dimer, reduced clot permeability, and reduced rate of increase in D-dimer levels during clot lysis 2

Clinical Implications

• Understanding the incomplete nature of natural thrombus resolution is crucial for clinical decision-making regarding anticoagulation duration 1
• Patients with persistent symptoms or risk factors for recurrence may benefit from extended anticoagulation therapy 3
• In patients with PE and systolic blood pressure ≥90 mmHg, direct oral anticoagulants are non-inferior to traditional therapy (heparin plus vitamin K antagonist) for treating PE and have a 0.6% lower rate of bleeding 3
• For patients with massive PE and hemodynamic instability (systolic BP <90 mmHg), thrombolytic therapy may be indicated to rapidly restore pulmonary blood flow 1, 3

Common Pitfalls and Caveats

• Assuming complete natural resolution of pulmonary emboli may lead to premature discontinuation of anticoagulation therapy 1
• Failing to recognize that persistent perfusion defects can contribute to long-term symptoms and functional limitations 1
• Overlooking the risk of CTEPH development in patients with persistent symptoms after PE 1
• Underestimating the risk of recurrent PE, particularly in patients with unprovoked events or prothrombotic conditions 1, 2