Investigating Potential Interactions Between Neurohypophyseal Peptides, their Drug Analogs, and Coagulation Factor VIII

Lawandi, A. Diss. Concordia University, 2014.

The neurohypophysis is known to secrete vasopressin during times of severe haemorrhage, and oxytocin during labour and delivery, events in which blood loss also occurs. Evidence suggests that there may be an interaction between these peptides and the coagulation cascade, and currently, desmopressin, a drug analog of vasopressin, is a first line therapy for mild Hemophilia A, a common coagulopathy. In this work, interactions between vasopressin and oxytocin with a crucial member of the coagulation cascade, the cofactor Factor VIII, were investigated using fluorescence spectroscopy, interference immunoassays, commercially produced Factor VIII activity kits, and equilibrium dialysis. The results suggest not only that the peptides interact with the coagulation factor, but do so in a way that enhances its activity and prolongs its active form half-life, as seen through the enhancement of the activity of the FXase complex by assay. This theory was then expanded to study the analogs of vasopressin and oxytocin, desmopressin and carbetocin, drugs currently used clinically in the treatment of hemorrhagic conditions. Similar results were obtained. On the whole, these results indicate a potential newly discovered role for the neurohypophyseal hormones, as well as their drug counterparts being used in clinical practice today and may suggest an expanded clinical use in the control of severe haemorrhage.

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