Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension.
Although the mechanisms involved in the pathophysiology of primary pulmonary hypertension have not yet been delineated, thrombosis has been implicated. This study was designed to determine whether thrombin activity as reflected by plasma concentrations of fibrinopeptide A (FPA), a marker of the action of thrombin on fibrinogen, is increased in patients with primary pulmonary hypertension. To evaluate fibrinolytic activity, we measured plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cross-linked fibrin degradation products. We studied 31 patients with primary pulmonary hypertension. Plasma FPA concentrations measured by radioimmunoassay, were elevated to 87.4 +/- 36.9 ng/ml (mean +/- SEM). Fifteen minutes after administration of heparin (5,000 U), FPA concentrations decreased to 6.8 +/- 1.4 ng/ml (p less than 0.001 compared with preheparin levels). In 21 of 30 patients (70%), FPA concentrations after heparin administration were less than half the preheparin levels, a response consistent with inhibition of thrombin by heparin and the short half-life of FPA. Despite evidence for marked thrombin activity, plasma concentrations of cross-linked fibrin degradation products were normal in all but four patients. Plasminogen activator inhibitor-1 activity was elevated in 19 of the 27 patients in whom it was measured, potentially limiting the fibrinolytic response. The elevations of FPA indicate that thrombin activity is increased in vivo in patients with primary pulmonary hypertension. Thus, sequential assays of plasma markers of thrombosis and fibrinolysis in vivo may help identify those patients who may benefit from treatment with anticoagulants.
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
P R
PR
Eisenberg
C
C
Lucore
L
L
Kaufman
B E
BE
Sobel
A S
AS
Jaffe
S
S
Rich
D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis*; D005342:Fibrinolysis; D005344:Fibrinopeptide A / Q000032:analysis*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D008171:Lung Diseases / Q000097:blood*; D015849:Plasminogen Inactivators / Q000032:analysis; D011446:Prospective Studies; D013927:Thrombosis / Q000097:blood*
D005338:Fibrin Fibrinogen Degradation Products; D015849:Plasminogen Inactivators; D005344:Fibrinopeptide A; D005340:Fibrinogen