Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis

Abstract

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.

Plasminogen Activator Inhibitor Type 1: Biochemistry and Evidence for Modulation of Fibrinolysis In Vivo

“…15,112 The venous occlusion test, in which the forearm is occluded for 10 or 20 minutes with the blood pressure cuff midway between the systolic and diastolic blood pressure is one way by which to determine if the t-PA can be released normally from the endothelium. 114,115 Venous occlusion does not cause a significant increase in PAI-1 antigen, 116,117 but induces a 10-to 20-fold in crease in t-PA antigen and activity. 118 Although PAI-1 antigen, which includes the level of active PAI-1 and PAI-1 complexed to t-PA, remains unchanged, the active PAI-1 may be neutralized by the increased t-PA. 116 Multiple factors influence the levels of t-PA and PAI-1 in plasma.…”

Haemostatic and inflammatory alterations in familial hypercholesterolaemia, and the impact of angiotensin II infusion

“…Plasma concentrations of haemostatic and inflammatory markers during interventions were corrected for changes in the haematocrit; correction factors were calculated from the following formula: 1-haematocrit intervention /1-haematocrit rest . 22 Enzyme immunoassay from Hyphen BioMed (Neuville sur Oise, France) was used to determine plasma concentrations of PAI-1 activity. Determination of PAP was performed by a classical two-site ELISA, described earlier.…”

Acquired Defects of Fibrinolysis Associated with Thrombosis

“…Elevated PAI-1 levels have been the most frequent finding. 23 - 24 An increase in PAI-1 has been considered as a predictive factor of post-operative thromboembolism in orthopedic surgery. 25,26 A decrease of t-PA and an increase in PAI-1 have been observed in patients after orthopedic surgery.…”