| Popis: |
DDAVP is used effectively to induce a haemostatic response in certain types of haemophilia A and von Willebrands disease, but the accompanying increase in fibrinolytic activity is an unwanted effect. Here we have quantified the extent and time course of changes in t-PA, its physiological inhibitor PAI and factor VIII moieties, using functional and immunometric assays, following i.v. and s.c. injection of DDAVP 0.4 ug kg-1 in 6 normal volunteers in a double blind crossover study.T-PA, factor VIII and vWF values increased after dosing and the area under the response versus time curve was higher after i.v. than s.c. injection. Conversely levels of PAI activity decreased, with lower minimum values for i.v. than s.c. and a correspondingly lower area under the response curve for the former route. In several subjects PAI activity fell to zero during the sampling period. The times to the first occurrence of maximum response were determined. The median values for factor VIII were 40 and 90 min for i.v. and s.c. respectively. For vWF they were 60 and 80 min. For t-PA activity they were 20 and 60 min indicating that the release of factor VIII and vWF was delayed compared with t-PA activity. PAI-1 antigen was assayed by ELISA to investigate clearance of PA inhibitor and was compared with changes in PAI activity during the infusion of DDAVP and after a subsequent venous occlusion.The results indicate that fibrinolytic and haemostatic responses follow different time courses from each other, both after i.v. and s.c. administration of DDAVP, that are reproducible from subject to subject. The use of specific assays has permitted determination of the fibrinolytic response to DDAVP to be assessed in terms of changes in pro and antifibrinolytic components. |
