Clinical study: thrombogenesis
Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage

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Abstract

OBJECTIVES

We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage.

BACKGROUND

Intra-atrial thrombogenesis is generally thought to be induced by blood stasis in the atrial appendage involved with atrial fibrillation (AF). Little attention has been paid to alterations of the endocardial endothelium on which the thrombus develops.

METHODS

Atrial appendage tissue was obtained at heart surgery or at autopsy from AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded.

RESULTS

In contrast to the apparent immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the endocardial endothelium was increased in most cardiac patients, particularly in the left, but not in the right, atrial appendage of patients with mitral valvular disease, irrespective of whether AF was present. Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium.

CONCLUSIONS

Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis.

Abbreviations

AF
atrial fibrillation
eNOS
endothelial nitric oxide synthase
GP Ib/IX
glycoprotein Ib/IX
GP IIb/IIIa
glycoprotein IIb/IIIa
IgG
immunoglobulin G
vWF
von Willebrand factor

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