Defense mechanism against intravascular clot formation is dependant upon the release of free tissue plasminogen activator (t-PA) from the vascular wall. To investigate this function a dynamic test is necessary to differenciate patients at risk of persistant thrombosis from patients who possess potential capacity to dissolve intravascular clots. In the present study, three different routes of administration of DDAVP and venous occlusion (VO) were applied to 9 healthy young volunteers in order to determine the best stimulus and the best test to assess individual capacity of releasing free t-PA in circulation. DDAVP was intravenously administered at a dose of 0,4 pg/kg body weight, and intranasally at a dose of 300 pg by two different preparations drops and spray. The same volunteers were also submitted to VO on 2 occasions after 1 H and after 10 mn of rest. In blood samples collected before and after the stimulation, t-PA activity and antigen, t-PA inhibitor (PAI) and euglobulin lysis time (ELT) were measured. Only one stimulus (IV DDAVP) and one test (t-PA activity in euglobulins) identified 100 per cent of normal subjects as capable of developing increased fibrinolytic activity. All other stimuli and especially VO pointed out absence of fibrinolytic response in several normal subjects, for exemple t-PA activity in euglobulins was found enhanced in all 9 subjects after IV DDAVP but in only five after VO. In addition, some tests such as ELT were found to be not sensitive enough to detect t-PA activity release. This study also showed that after DDAVP injection, PAI abruptly decreased in correlation with the release of t-PA activity. However t-PA activity can reach high levels in blood although PAI is still measurable suggesting that after release t-PA activity is not immediatly inhibited by PAI and that they can both coexist. These results demonstrate that the choice of the stimulus and the test to measure fibrinolytic activity have to be carefully determined to identify patients at risk of persistent thrombosis.
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