VASOPRESSIN AND THE REGULATION OF FIBRINOLYSIS: HAEMOSTATIC RESPONSES TO HYPOTENSION IN THE ABSENCE OF ADRENALINE RELEASE

Vasopressin (aVP) infusions resulting in plasma concentrations that simulate those during stress cause increases in factor VIII (EVTII) and plasminogen activator activity (PAA). During apcmorphine induced nausea and abdominal surgery similar increases in aVP are associated with elevated FVIII and PAA suggesting aVP is a mediator of haemostatic function. However during stress there is release of adrenaline which has similar effects on haemostasis. The aim of this study was to investigate the effects of endogenous aVP release on haemostasis in patients with postural hypotension (a potent stimulus to aVP release) due to autonomic neuropathy who have absent circulating adrenaline. The study was performed in i) three patients with progressive autonomic failure (PAF) who release aVP but not adrenaline ii) three patients with PAF with multi-system atrophy (MSA, the Shy-Drager syndrome) who have deficient release of both aVP and adrenaline. After lying down overnight patients stood for 2 minutes on 3 occasions at 1 hour intervals. Samples were taken for aVP, adrenaline, ECLT and FVIII. In PAF mean blood; pressure fell from 108 lying to 47 irmHg standing. Pulse did not change. aVP rose from 1.2 lying to 56 pg/ml standing. Plasma adrenaline was sub-normal throughout. Median PAA (10⁶ /ECLT² ) lying was 92 and rose on standing to 376 units and correlated with plasma aVP (r = 0.87, p < 0.0001). In PAF with MSA mean blood pressure fell from 107 lying to 61 irmHg standing. aVP levels did not change and adrenaline remained below normal. PAA rose from a median 30 lying to 87 units standing. No change in FVIII was observed in either group. The results suggest that aVP regulates plasminogen activator activity in the absence of adrenaline. The lack of a rise in FVIII suggests that circulating adrenaline may be necessary for aVP to exert an effect on FVIII concentrations.