Pulmonary Embolus: Light and Electron Microscopy may Change Treatment Algorithms

Purpose: Medical literature describes the histology of pulmonary emboli, obtained from cadaveric specimens. The recent availability of percutaneous embolectomy devices provides an opportunity to examine pulmonary embolus (PE) specimens in vivo.  This study was undertaken to study the age and composition of pulmonary emboli samples with light and electron microscopy.

Materials and Methods: 25 embolectomy specimens were sent for light microscopy (LM) or electron microscopy (EM), or both. Chronic appearing portions (firm, pale pink, and tan) and along with newer (soft, dark red) samples were sent for LM and EM.  A comparison with photographs of the gross specimens was performed, in most cases.  A review of photomicrographs was performed with the pathologist and electron microscopist.

Results: 50-70% PE samples demonstrated at least some gross features of chronicity including areas of lighter red-pink or tan-white color, as well as portions of thrombus, which felt grossly firm and "rubber-like".  

LM images demonstrated: 

1. Layering and hyalinization

2. Lines of Zahn 

3. Endothelialization

4. Revascularization

5.  Collagenization

EM showed:  

1. Thickened, frayed and disorganized fibrin

2. Dense sheets of compacted fibrin

3. Phagocytosis

4. Liposomes

5. Neutrophile extracellular traps (NETS)

Conclusion: LM and EM demonstrate heterogenous age of most thromboemboli, consistent with gradual progressive accumulation in deep veins over many days to weeks.  Dense sheets of fibrin and endothelialization, collagenization, thickened fibrin strands, and diffuse inflammation indicate older organized thombus, which is very different from fresh thrombus.  The authors believe this older, thickened, chronic thrombus, containing insoluble cross-linked fibrin strands is unlikely to resolve with either the intrinsic fibrinolytic system or extrinsic plasminogen activators.   Treatment of PE with anticoagulation alone, or even therapeutic thrombolytic infusions, may be ineffectual based on these findings.  Additionally, diffuse inflammation suggests organization and residual arterial luminal narrowing.  This may help explain why 4-6% of patients who survive initial PE suffer from chronic thromboembolic pulmonary hypertension (CTEPH) and 30-43% have a long-term pulmonary disability. 

These microscopic findings, along with better understanding of imaging correlation may provide us the ability to stratify care among the multiple options of PE treatment (i.e anticoagulation, thombolytics, and embolectomy) currently at our disposal.