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

D E Newby, A Stewart, F N Witherow, S Grieve, P Dawson, K A Fox, D J Webb, C A Ludlam

Research output: Contribution to journalArticlepeer-review

Abstract

Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose 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). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly 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.

Original languageEnglish
Pages (from-to)195-203
Number of pages9
JournalThrombosis and Haemostasis
Volume84
Issue number2
Publication statusPublished - Aug 2000

Keywords

  • Adult
  • Deamino Arginine Vasopressin
  • Dose-Response Relationship, Drug
  • Factor VIII
  • Forearm
  • Hemodynamics
  • Humans
  • Infusions, Intra-Arterial
  • Interleukin-6
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1
  • Substance P
  • Time Factors
  • Tissue Plasminogen Activator
  • von Willebrand Diseases
  • von Willebrand Factor

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