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Thromb Haemost 2000; 84(02): 195-203
DOI: 10.1055/s-0037-1613996
Review Article
Schattauer GmbH

Local and Systemic Effects of Intra-arterial Desmopressin in Healthy Volunteers and Patients with Type 3 von Willebrand Disease

Role of Interleukin-6
David E. Newby
1   From the Clinical Pharmacology Unit and Research Centre, Edinburgh, UK
2   Cardiovascular Research, Department of Cardiology, Edinburgh, UK
,
Andrew Stewart
3   Department of Haematology, University of Edinburgh, Western General Hospital, Edinburgh, UK
,
Fraser N. Witherow
2   Cardiovascular Research, Department of Cardiology, Edinburgh, UK
,
Susan Grieve
2   Cardiovascular Research, Department of Cardiology, Edinburgh, UK
,
Pamela Dawson
3   Department of Haematology, University of Edinburgh, Western General Hospital, Edinburgh, UK
,
Keith A. A. Fox
2   Cardiovascular Research, Department of Cardiology, Edinburgh, UK
,
David J. Webb
1   From the Clinical Pharmacology Unit and Research Centre, Edinburgh, UK
,
Christopher A. Ludlam
3   Department of Haematology, University of Edinburgh, Western General Hospital, Edinburgh, UK
› InstitutsangabenThis work was supported by the British Heart Foundation. DJW is supported by a Research Leave Fellowship from the Wellcome Trust (WT 0526330).
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Publikationsverlauf

Received 26. Januar 2000

Accepted after revision 16. März 2000

Publikationsdatum:
14. Dezember 2017 (online)

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Summary

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 ≥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 ≥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.

Keywords

Plasminogen activators - desmopressin - von Willebrand factor - interleukin-6 - factor VIII:C
 

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