Thrombo-CARE-cardioembolic stroke etiology in cryptogenic stroke suggested by fibrin-/platelet-rich clot histology : Thrombo-CARE (configuration analysis to refine etiology)

Background: Despite extensive diagnostic efforts, the etiology of stroke remains unclear in up to 30% of patients. Mechanical thrombectomy (MT) potentially enhances etiological determination by (immuno)histological analysis of retrieved thrombotic material.

Methods: In this monocentric exploratory study, clots from 200 patients undergoing MT were investigated by hematoxylin and eosin, CD3, and CD45 staining. Semiquantitative and computer-based image analysis defined the histological composition and relative fractions of immunohistochemically stained areas. First, we correlated these results with strokes of known etiology. Subsequently, clots of unknown source were characterized with regard to their (immuno)histological profile to attempt etiological classification.

Results: Samples from 198 patients were accessible for analysis. Fibrin-/platelet-rich histology appeared in 45 (23%), erythrocyte-rich in 18 (9%), and mixed histology in 123 (62%) patients. Etiology was classified as cardioembolic in 87 (44%), arterioembolic in 37 (19%), and as cryptogenic stroke (CS) in 26 (13%) cases. 20 (23%) patients with cardioembolic stroke and 5 (14%) patients with arterioembolic stroke had fibrin-/platelet-rich clots. 8 (22%) patients with arterioembolic stroke and 1 (1%) patient with cardioembolic stroke had erythrocyte-rich clots. In CS, cardioembolic clot features appeared more than twice as often as arterioembolic clot features. Whereas the association between histology and etiology was significant (p = 0.0057), CD3/CD45 staining did not correlate.

Conclusion: A significant association between histology and etiology was observed, with the proportion of erythrocyte-rich thrombi being largest among arterioembolic strokes and the proportion of fibrin-/platelet-rich thrombi highest among cardioembolic strokes. A high number of clots from CS presented histological features of cardioembolic clots. Thus, patients with CS and fibrin-/platelet-rich clots particularly require long-term cardiac rhythm monitoring and may benefit from oral anticoagulation.