Coagulation and fibrinolytic parameters in patients with pulmonary hypertension

Vascular endothelium reacts to various pathophysiologic stimuli by releasing several autocoids and cytokines that can be used along with the coagulation and fibrinolytic markers for the diagnosis of hemostatic alterations. Several newer markers for vascular distress, such as tissue plasminogen activator (TPA), tissue plasminogen activator inhibitor-1 (PAI-1), TPA/PAI-1 complex, and the newly reported inhibitor of the coagulation process, namely, tissue factor pathway inhibitor (TFPI), have been implicated in the pathogenesis of pulmonary hypertension.

To investigate the behavior of endothelial cells at basal and time-dependent venous stasis-induced changes, various markers were measured in patients with primary and secondary pulmonary hypertension and compared with healthy human volunteers (controls) without any family history of thromboembolism or history of hypertensive disorders. The right atrial pressure (RAP) and pulmonary arterial pressure were measured and the hemostatic parameters were correlated to determine the relevance of these parameters with the alterations in the present indices.

A fibrinolytic deficit exists in patients with pulmonary hypertension, indicated by the prolongation of the euglobulin clot lysis time at basal conditions and after the venous occlusion test. This defect was mainly due to increased production of PAI-1 by endothelium (patients 59.8 +/- 22.3 AU/ml; controls 30.3 +/- 14.5 AU/ml; p = 0.005). We also report for the first time that a decrease in tissue factor pathway inhibitor antigen was also observed in these patients when RAP was > 9 mmHg [controls 95.6 +/- 61.6 ng/ml; patients with RAP > 9 mmHg 47.2 +/- 19.2 ng/ml (p = 0.044); patients with RAP > 9 mmHg 96.6 +/- 32.4 ng/ml (p = 0.002 compared with patients with RAP > 9 mmHg)], indicating endothelial cell and hemostatic disturbances.

We conclude that the euglobulin clot lysis time was prolonged in patients with pulmonary hypertension compared with controls. The impairment of the fibrinolytic system was due to an elevated concentration of PAI-1. In RAP > 9 mmHg, an additional prothrombotic factor is the decrease in plasma tissue factor pathway inhibitor antigen. It appears from this study that antithrombotic treatment is indicated in these patients.