title: Plasma coagulation profiles in patients with severe primary pulmonary hypertension.
abstract: Patients with primary pulmonary hypertension (PPH) benefit from treatment with anticoagulants, and histological findings suggest that in situ thrombosis of pulmonary vessels contributes to the pathogenesis of this disease. The mechanisms that cause a hypercoagulable state in the pulmonary vascular bed have not been fully investigated. This study compared plasminogen plasma activity, protein C and protein S plasma activities, fibrinogen and fibrin degradation products (FGDP and FBDP, respectively), von Willebrand factor antigen (vWF-Ag), prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) in 16 patients with PPH and in 16 healthy volunteers. In a subset of the PPH patients, these variables were also compared in simultaneously-obtained mixed-venous and arterial blood samples. Proteins C and S, FGDP, FBDP, and plasminogen levels as well as plasma concentrations of prothrombin fragment F1.2 and TAT were normal in the 16 patients with PPH. In contrast, the plasma activity of PAI was significantly elevated (p<0.0001). Arterial PAI levels were considerably higher than mixed venous PAI levels (p=0.0018), which may reflect intrapulmonary production. Furthermore, vWF-Ag levels were significantly elevated (p<0.0001), but there was no significant difference between mixed-venous and arterial blood. These data, on the whole, do not suggest increased thrombin activity in patients with primary pulmonary hypertension. However, the markedly elevated levels of plasminogen activator inhibitor as well as its transpulmonary gradient may provide a clue to locally impaired fibrinolysis in the pulmonary vascular bed.
authors.affiliation: Division of Pulmonary Medicine, Hannover Medical School, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: M
authors.initials: M
authors.lastname: Sosada
authors.forename: H
authors.initials: H
authors.lastname: Fabel
mesh_terms: D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D010447:Peptide Hydrolases / Q000032:analysis; D015849:Plasminogen Inactivators / Q000097:blood; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D013917:Thrombin / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D015849:Plasminogen Inactivators; D011486:Protein C; D017293:Protein S; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin