Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease - Role of interleukin-6

Intra-arterial desmopressin caused dose and time dependent increases (p <0. 001 for all) in forearm blood flow tall doses) and plasma tissue plasminoge n activator (t-PA) concentrations (desmopressin greater than or equal to 70 ng/min). Although plasma t-PA concentrations rose in both forearms, then w as a modest local release of t-PA in the infused forearm (14 ng/100 mt of t issue/min, p <0.05). At desmopressin doses greater than or equal to 300 ng/ min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations ro se in both forearms (p <0.001) and correlated with the rise in interleukin- 6 concentrations (r = 0.92, p <0.001; r = 0.85, p = 0.002 respectively). Ne ither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C releas e in the patients, although desmopressin increased plasma interleukin-6 con centrations as in healthy volunteers. We conclude that desmopressin release s t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, Possib ly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.