Effects of physiological concentrations of vasopressin on haemostatic function in man

Abstract

1. Plasma concentrations of vasopressin (aVP) attained under conditions of stress were simulated by infusing four volunteers with 0.25, 0.5, 1.0 and 2.0 pressor units of aVP over 1 h (units/h). Three subjects had all four infusions and one received only 1.0 unit/h. 2. Blood samples were taken for assay of factor VIII coagulant activity (FVIIIC), factor VIII related antigen (FVIIIRAg), the ristocetin cofactor (FVIIIRiCof), euglobulin lysis time (ELT) and aVP concentrations before infusion (time 0) and every 20 min for 80 min. Fibrinopeptide A (FPA) generation time was measured at time 0, 60 and 80 min. 3. At infusion rates of 0.25 unit/h median aVP levels peaked at 6.5 pg/ml and there was no change in haemostatic function. At 0.5 unit/h aVP levels peaked at 16.0 pg/ml, there was no change in FVIII or FPA generation time, and plasminogen activator activity (106/ELT2) rose from 100 to 400 units. At 1.0 unit/h, aVP levels rose to 25.4 pg/ml, FVIIIC rose by 160% and activator activity from 87 to 360 units. At 2.0 units/h, aVP concentrations reached 83 pg/ml, there was an increase in all modalities of FVIII and activator activity rose from 251 to 452 units. FPA generation time shortened and circulating plasma levels of FPA were increased. 4. There was a highly significant correlation between the percentage increases in all three components of FVIII and plasma aVP levels (FVIIIC: r = 0.87, P < 0.0001; FVIIIRAg: r = 0.61, P < 0.0001; FVIIIRiCof: r = 0.80, P < 0.0001) and between the increase in plasminogen activator activity and aVP levels (r = 0.56, P < 0.0001). 5. The results indicate that plasma concentrations of aVP comparable with those attained during stress cause a rise in FVIII, an increase in plasma activator activity and effects on FPA generation consistent with low-level activation of the coagulation mechanism. Endogenous vasopressin could mediate alterations in haemostatic function known to accompany events such as surgical operations.