COAGULATION AND FIBRINOLYTIC PROFILES IN PATIENTS WITH SEVERE PULMONARY-HYPERTENSION

Study objectives: Although in situ thrombosis is a prominent finding i n lung vessels from patients with primary and secondary pulmonary hype rtension, to our knowledge, plasma coagulation factors that might cont ribute to a hypercoagulable state have not been fully investigated. We hypothesized that the local coagulation environment in the lung vascu lature is important to progression if not initiation of pulmonary hype rtension. Design: Quasi-experimental cross-sectional design with concu rrent controls. Setting: Referral clinics and inpatient services of a University Hospital and a Veterans Administration Medical Center. Part icipants: To investigate the role of plasma coagulation factors in sev ere pulmonary hypertension, we sampled plasma from patients with prima ry pulmonary hypertension, patients with pulmonary hypertension second ary to a discernible etiology, and normal adult control subjects. Resu lts: We detected abnormalities of the thrombomodulin/protein C anticoa gulant system, evidenced by a decrease in soluble thrombomodulin, in p atients with primary pulmonary hypertension, In the patients with prim ary pulmonary hypertension, we found impaired fibrinolytic activity, w ith a rise in the fibrinolytic inhibitor plasminogen activator 1 and e levated euglobulin lysis time. Lower fibrinolytic activity correlated with high mean pulmonary artery pressure, In contrast, in patients wit h secondary pulmonary hypertension, von Willebrand factor antigen and fibrinogen levels were increased, and fibrinolytic activity decreased. Conclusions: Different patterns of coagulation and fibrinolytic abnor malities are apparent in plasma from patients with primary and seconda ry pulmonary hypertension. Although we are unable to address causality with this study, we speculate that abnormalities of these coagulation mechanisms may initiate or play a role in perpetuation of pulmonary h ypertension.