Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing's syndrome

Abstract

Glucocorticoids are known to increase plasma concentrations of factor VIII (FVIII) and von Willebrand factor (vWF), and their administration is associated with an increased incidence of thrombotic complications. Because Cushing's syndrome is characterized by an endogenous increase in glucocorticoids, we studied levels of FVIII and vWF in 20 patients with Cushing's syndrome. Plasma levels of FVIII and vWF were found to be markedly increased. Moreover, the molecular organization of plasma vWF appeared to have been altered by the presence of unusually large multimers, normally present only in the cellular compartments. Spontaneous platelet aggregation and hyperresponsiveness to ristocetin were also observed. All patients underwent therapeutic surgery. Within 1 month of the intervention, regardless of its efficacy as evaluated by the assay of plasma and urinary Cortisol, an additional significant increase in levels of FVIII and vWF was observed, with a concomitant more pronounced representation of abnormally large vWF multimers in circulation. In the cured patients, a progressive decrease in the levels of FVIII and vWF was observed, beginning in the third month after surgery, with complete normalization of the pattern within 12 months of surgery; a concomitant improvement in the plasma vWF multimer pattern was also observed. In contrast, no significant changes in FVIII or vWF were found in patients with persistent Cushing's syndrome. Our findings emphasize that vWF abnormalities are also part of the prothrombotic state of Cushing's syndrome. Moreover, this study also identified a period of additional thrombotic risk immediately after surgery, as a result of the worsening of the hemostatic pattern.