Chest
clinical investigationsCoagulation and Fibrinolytic Profiles in Patients With Severe Pulmonary Hypertension
Section snippets
Population
We enrolled patients from University of Colorado Health Sciences Center, Denver Veterans Administration Medical Center, and normal control subjects. Patients with PPH were evaluated in the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center. All potential PPH patients underwent right heart catheterization prior to enrollment and were carefully classified as having PPH after exclusion of other causes by history, radiography, ventilation perfusion scanning,
Results
Demographic characteristics of the patients are displayed in Table 1. The age of the subjects with pulmonary hypertension from secondary causes was significantly greater than for PPH patients or control subjects (p>0.01). There were no significant differences in smoking status or gender of subjects by χ2 analysis (Table 1).
Diseases associated with SPH included COPD (five patients), obstructive sleep apnea (four patients), obesity/hypoventilation (five patients), restrictive lung disease (two
Patient Hemodynamics
Thirteen of the 25 SPH and 12 of 12 PPH patients had complete hemodynamic data during right heart catheterization. There were clear differences in pulmonary vascular hemodynamics and respiratory parameters between the patients with PPH and SPH. Mean pulmonary artery pressure and pulmonary vascular resistance were significantly higher in the PPH group (Table 2). Systolic, but not mean, aortic pressures were higher in the SPH group. Spirometry values were lower for the group of patients with SPH.
Protein C/TM System
Plasma TM was significantly decreased in patients with PPH (p>0.02) compared to both control subjects and patients with SPH (Fig 2, Table 3). There was no difference in APC activity among groups, and there was no correlation between soluble TM and APC activity (Spearman rank coefficient p=0.12). Protein C and protein S levels were not lower than control in the PPH and SPH groups. The presence of APC resistance was similar among groups, with one third of subjects in each group, including control
Fibrinolytic Activity
ELT for patients with both PPH and SPH was significantly prolonged compared to that for control subjects (Fig 3). PAI−1 levels were significantly higher in PPH compared to SPH patients and control subjects (Fig 4). tPA levels were not different among groups, although there was a trend to elevation in the SPH group (Table 3; p=0.09). There were no differences in α2−antiplasmin or plasminogen among groups.
There was a linear correlation between loss of fibrinolytic activity and increased pulmonary
vWF Antigen and Activity
There were increased vWF antigen levels in the group with SPH compared to control subjects (Table 3, p>0.01). Ristocetin activity showed a trend to increase in the SPH group (Table 3, p=0.054). There was a disparity between vWF antigen levels and ristocetin activity for SPH patients with pulmonary hypertension, with significantly higher antigen vs activity levels (paired t test, p>0.05) for the SPH patients (190±19% vs 142±14%) but not control subjects (104±16% vs 105±10%) or the PPH group
Coagulation Activation Markers and Activation Inhibitors
There were no differences in F1.2 and TAT levels between groups (Table 3). Antithrombin III and tissue factor pathway inhibitor levels showed no differences among groups (Table 3). Tests of activation of coagulation (TAT, F1.2) failed to correlate with mean pulmonary artery pressure.
In 22 patients, clinical laboratory assays of bilirubin, serum glutamic oxaloacetic transaminase (SGOT), and uric acid were available for analysis. By linear regression analysis, vWF and tPA levels correlated with
Discussion
In situ thrombosis is a prominent finding in lung vessels from patients with PPH and SPH. Precise mechanisms of this finding are not defined, but likely include an altered procoagulant/fibrinolytic balance in the pulmonary circulation, with resultant thrombus formation. In this study, we investigated several aspects of coagulation in the plasma of three groups of subjects, patients with PPH and SPH, and normal control subjects: the protein C natural anticoagulant system, fibrinolytic activity,
Acknowledgments
The authors wish to acknowledge Kristinne Wynne for her help with patient recruitment and to Norbert F. Voelkel, MD, for his support.
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This project was supported in part by a grant from the Department of Veterans Affairs (MERIT Review Grant to Dr. Marlar) and in part by the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center.