Deficient t-PA Release and Elevated PA Inhibitor Levels in Patients with Spontaneous or Recurrent Deep Venous Thrombosis

Abstract

SummaryThe fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V. O.). On the basis of the results, the patients could be classified in 3 groups:good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32).The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p <0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p <0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients.It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients. Poor responders however fall into two categories, one fourth with deficient t-PA release who have a high risk for recurrent venous thrombosis, and three fourth with increased PA-Inhibitor levels which may be associated with underlying diseases also causing hypertriglyceridemia. Further elucidation of the correlation between recurrent venous thrombosis and deficient fibrinolysis is expected to result in more specific and adequate treatment and prevention of DVT.

Endothelial fibrinolytic reactivity and the risk of deep venous thrombosis after spinal cord injury

“…14,16,17 Using this test, decreased ®brinolytic capacity measured in the upper limb has been found in 35% of patients with recurrent thromboembolism. 18 The venous occlusion test is typically applied to the upper limbs but in this case we have adapted the test to study the reactivity of the veins of the lower limbs. Thus, venous occlusion using similar pressures produces dierent eects in the upper and in lower limbs, characterized by a release of lower amounts of endothelial factors (such as tPA) in the lower limbs than in the upper limbs in healthy volunteers 14 as well as in spinal cord injury patients contrary to Keber's study which shows a recovery of ®brinolytic activity in spinal cord injury patients.…”

Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway

“…A major function of PAI-1 is the inactivation of tissue-type plasminogen (tPA) and urokinase-type plasminogen (uPA) activators, through covalent binding of PAI-1 to tPA or uPA, resulting in decreased plasmin activity and fibrinolytic potential (1)(2)(3). Through its involvement in the fibrinolytic pathway, PAI-1 has been shown to play a significant role in thrombotic-induced diseases, including venous thrombosis (4,5) and the acute coronary syndrome, wherein serum levels of PAI-1 increase upon coronary occlusion and predict future coronary events in human subjects (6 -8). More recently, however, PAI-1 has been shown to regulate cell migration, thereby suggesting that PAI-1, in addition to its role in the fibrinolytic pathway, may also modulate cellular recruitment during the acute inflammatory process (9 -15).…”

Purification and characterization of natural and recombinant human plasminogen activator inhibitor‐1 (PAI‐1)

“…PAI-2 appears in plasma during pregnancy, but its physiological role remains unclear. PAI-1, on the other hand, is increased in many clinical conditions [I 71, including venous thromboembolic disease [18].…”