Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis.
In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and fibrinolytic activity were measured in these samples. During venous stasis, plasminogen activator inhibitor (PAI) activity decreased in almost all patients (81 of 83), from a median value of 8.2 to 2.9 U/mL (P less than .001, Wilcoxon signed-rank test). Because PAI-1 antigen augmented from a median value of 16 to 19.2 ng/mL (P less than .001), the decline in PAI activity was attributed to an increase in t-PA antigen from a median value of 10 to 21.7 ng/mL (P less than .001). Neutralization of PAI activity thus reflects the patient's capacity to overcome basal inhibitory potential through t-PA release. Based on residual PAI activity after 10-minute stasis, patients were classified as good or bad responders (PAI activity below detection limit, ie, less than or equal to 1.0 and greater than 1.0 U/ml, respectively). Good responders had a significantly higher fibrinolytic response after stasis than bad responders (median euglobulin clot lysis time 60 v 180 minutes; dilute whole blood clot lysis time 60 v 120 minutes; fibrinolytic activity on fibrin plates 7.7 v 0 U/mL). Furthermore, good responders, as compared with bad responders, had higher t-PA release (median 16.5 v 11.5 ng/mL), lower basal PAI activity (median 4.8 v 11.2 U/mL), and lower basal PAI-1 (median 11 v 21 ng/mL) and u-PA antigen (median 7.9 v 9.0 ng/mL, P less than .02). Hypofibrinolysis, as defined by the inability of released t-PA to overcome PAI-1 basal inhibitory potential, was observed in 45 of 83 patients (54%) and resulted either from an insufficient release of t-PA or from an increased basal PAI activity.
D000328:Adult; D000368:Aged; D005260:Female; D005342:Fibrinolysis; D006023:Glycoproteins / Q000032:analysis*; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000032:analysis; D015849:Plasminogen Inactivators; D013924:Thrombophlebitis / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator