Circulation, Vol 86, 1241-1248, Copyright © 1992 by American Heart Association
MA Olman, JJ Marsh, IM Lang, KM Moser, BR Binder and RR Schleef
BACKGROUND. Chronic thromboembolic pulmonary hypertension (CTEPH) is a
disorder characterized by pulmonary arterial hypertension as a consequence
of organized thrombotic material in the central pulmonary arteries.
Incomplete resolution of acute pulmonary emboli is believed to be
pathogenically important; however, the mechanism for poor thrombus
dissolution remains to be explained. We undertook this study to assess the
major determinants of plasma fibrinolysis in patients with CTEPH (n = 32).
METHODS AND RESULTS. Immunological and functional levels of tissue-type
plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor
(PAI-1) were quantified in platelet- poor plasma (PPP) from patients with
CTEPH as well as age-matched controls. Although basal PPP t-PA antigen
levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen
levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in
the CTEPH group, no between-group differences were detected in the
enzymatic activities of these two molecules. The CTEPH group demonstrated a
greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean
rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean
rise, 1.2 IU/ml) than controls in response to an experimentally induced
venous occlusion. Immunoprecipitation and fibrin autography of PPP from two
patients with markedly elevated basal t-PA antigen levels demonstrate that
the t-PA antigen was present in PPP primarily in complex with PAI-1.
CONCLUSIONS. Although abnormalities of the fibrinolytic system were
detected, neither a high resting plasma PAI-1 activity nor a blunted
response of t-PA to venous occlusion can be invoked as an etiology for
CTEPH.
ARTICLES
Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension
Division of Pulmonary and Critical Care Medicine, University of California, San Diego.
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