EVIDENCE FOR PLASMIN-MEDIATED FIBRINOLYSIS AFTER RELEASE OF TISSUE PLASMINOGEN-ACTIVATOR BY DESMOPRESSIN INFUSION

A relationship between tPA activity and plasmin-mediated fibrinolysis in vivo (plasma levels of Bβ15-42-containing peptides) has been suggested by our previous studies: inverse correlations of Bβ15-42 levels with obesity and triglyceride levels (both associated with high tPA inhibition) in an epidemiological study; and increased levels of Bβ15-42 following improved control of diabetes, or treatment with oral or intramuscular stanozolol (which decrease tPA inhibition). The aim of the present study was to establish whether or not intravenous infusion of desamino-D-arginine vasopressin (DDAVP, desmopressin) is followed by increases in plasmin-mediated fibrinolysis in vivo (plasma Bβ15-42 levels). Desmopressin (0.3 μg/kg body weight) was infused intravenously over 15 mins in 22 subjects. Venous blood was obtained by separate venepuncture before and 15 mins after the end of the infusion, for assay of plasminogen activator activity of the euglobulin fraction on fibrin plates, tPA activity, and Bβ15-42 levels (RIA,IMCO). 18 subjects showed normal increases in fibrin plate lysis and in tPA activity after desmopressin (median tPA activity 120 mU/ml pre-, 5000 mU/ml post-infusion, p<0.001). In these 18 subjects, Bβ15-42 levels rose significantly (median 1.5pmol/ml pre-, 4.2 pmol/ml post-infusion, p<0.001). Four subjects showed no significant increases in fibrin plate lysis or in tPA activity after desmopressin (non-responders): all had significantly elevated levels of tPA-inhibition. In these 4 subjects no increases in Bβ15-42 levels were observed. In one nonresponder, who suffered a large myocardial infarction due to angiographic thrombosis with no atheroma at the age of 22 years, long-term treatment with stanozolol normalised the high level of tPA-inhibition, as well as the fibrin plate lysis and tPA activity responses to desmopressin: Bβ15-42 level then showed a normal response after desmopressin infusion (2.2 to 5 pmol/ml). We conclude that desmopressin infusion increases plasmin-mediated fibrinolysis in vivo, but only in the presence of normal increases in tPA activity.