Atrial fibrillation and thrombosis: immunohistochemical differences between in situ and embolized thrombi.
OBJECTIVE
Thromboembolism secondary to atrial fibrillation accounts for approximately one-fourth of all strokes. Although considerable resources have been targeted to pharmacologic prophylaxis, neither the cellular nor the biochemical composition of atrial thrombi is known. Quantitative immunohistochemistry was undertaken to define the composition of atrial thrombi and to explore morphological differences between atrial appendage thrombi and those that embolize.


METHODS
Serial sections of thrombi obtained during valve replacement surgery or embolectomy from 22 patients with atrial fibrillation were stained with antibodies against fibrin, integrin beta3, or tissue factor and analyzed with NIH-image.


RESULTS
Thrombi showed distinct regions staining for either fibrin or platelets and on average, the fibrin-rich regions predominated (P < 0.0001). The platelet content of embolized thrombi was nearly twice that of atrial thrombi (P = 0.02). Non-staining amorphous material comprised nearly half of atrial thrombi in situ, but was rare in embolized thrombi (P < 0.001). Tissue factor colocalized to areas rich in platelets and granulocytes.


CONCLUSIONS
The abundance of fibrin relative to platelets underscores the enhanced efficacy of warfarin prophylaxis in clinical trials. The finding of tissue factor localized to platelet-leukocyte clusters suggests its blood-borne origin. Compositional differences between in situ and embolized thrombi suggest directions for investigating propensity for embolization.
Wysokinski
W E
WE
Division of Cardiovascular Medicine, Mayo Clinic and Foundation for Education and Research, Rochester, MN 55905, USA. mcbane.robert@mayo.edu
Owen
W G
WG
Fass
D N
DN
Patrzalek
D D
DD
Murphy
L
L
McBane
R D
RD
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy; D001792:Blood Platelets / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006350:Heart Valve Prosthesis; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000378:metabolism; D008297:Male; D013923:Thromboembolism / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D039661:Integrin beta3; D014859:Warfarin; D005337:Fibrin; D013925:Thromboplastin