Increase in thrombomodulin concentrations after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension

STUDY OBJECTIVES: The objectives of the study were as follows: (1) to identify differences in endothelial dysfunction and altered hemostasis in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared with patients with acute pulmonary thromboembolism (APTE) uncomplicated by pulmonary arterial hypertension, by measuring the concentrations of thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, and other plasma factors of coagulation and fibrinolysis; and (2) to examine the effects of thromboendarterectomy on TM levels as a parameter of endothelial cell injury leading to abnormal hemostasis as well as to examine the clinical significance of TM as a marker of endothelial injury. DESIGN: Prospective comparison of concentrations of TM and other plasma parameters among patients with CTEPH or APTE and control subjects. PARTICIPANTS: We studied 22 healthy subjects (ie, control subjects), 22 patients who had been clinically stabilized after APTE, and 44 patients with CTEPH. In 21 of the patients with CTEPH, measurements were repeated after they had undergone pulmonary thromboendarterectomy. MEASUREMENTS AND RESULTS: Plasma concentrations of soluble TM in patients with CTEPH were measured and compared with those in patients with APTE. The mean (+/- SD) TM concentration in the CTEPH group (2.5 +/- 0.7 ng/mL) was significantly lower than that in the control group (4.0 +/- 0.6 ng/mL; p < 0.05). In contrast, the mean plasma TM concentration in the APTE group (4.6 +/- 1.9 ng/mL) was similar to that in the control group. After patients underwent pulmonary thromboendarterectomy, the mean TM concentration increased from 2.0 +/- 0.4 to 2.9 +/- 0.7 ng/mL (p < 0.05). In the CTEPH group, the plasma TM concentration was negatively correlated with mean pulmonary arterial pressure and total pulmonary resistance (p < 0.05). CONCLUSIONS: A decreased plasma TM concentration may reflect pulmonary vascular endothelial dysfunction leading to altered anticoagulant and fibrinolytic function in CTEPH, which rarely develops after APTE. Plasma TM measurements may be useful in distinguishing CTEPH with severe pulmonary hypertension from recurrent APTE.