Coagulation and fibrinolytic profiles in patients with severe pulmonary hypertension.
OBJECTIVE
Although in situ thrombosis is a prominent finding in lung vessels from patients with primary and secondary pulmonary hypertension, to our knowledge, plasma coagulation factors that might contribute to a hypercoagulable state have not been fully investigated. We hypothesized that the local coagulation environment in the lung vasculature is important to progression if not initiation of pulmonary hypertension.


METHODS
Quasi-experimental cross-sectional design with concurrent controls.


METHODS
Referral clinics and inpatient services of a University Hospital and a Veterans Administration Medical Center.


METHODS
To investigate the role of plasma coagulation factors in severe pulmonary hypertension, we sampled plasma from patients with primary pulmonary hypertension, patients with pulmonary hypertension secondary to a discernible etiology, and normal adult control subjects.


RESULTS
We detected abnormalities of the thrombomodulin/protein C anticoagulant system, evidenced by a decrease in soluble thrombomodulin, in patients with primary pulmonary hypertension. In the patients with primary pulmonary hypertension, we found impaired fibrinolytic activity, with a rise in the fibrinolytic inhibitor plasminogen activator 1 and elevated euglobulin lysis time. Lower fibrinolytic activity correlated with high mean pulmonary artery pressure. In contrast, in patients with secondary pulmonary hypertension, von Willebrand factor antigen and fibrinogen levels were increased, and fibrinolytic activity decreased.


CONCLUSIONS
Different patterns of coagulation and fibrinolytic abnormalities are apparent in plasma from patients with primary and secondary 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 hypertension.
Welsh
C H
CH
Denver Veterans Administration Medical Center, Department of Medicine.
Hassell
K L
KL
Badesch
D B
DB
Kressin
D C
DC
Marlar
R A
RA
D000328:Adult; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis*; D001794:Blood Pressure; D003430:Cross-Sectional Studies; D005260:Female; D005342:Fibrinolysis; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000503:physiopathology; D012119:Respiration; D014841:von Willebrand Factor / Q000032:analysis
D001779:Blood Coagulation Factors; D014841:von Willebrand Factor