fibrinopeptide-a and Hypertension--Pulmonary

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

Topics: Antithrombin III; Blood Coagulation; Fibrinopeptide A; Humans; Hypertension, Pulmonary; Mitral Valve Stenosis; Peptide Hydrolases

Intravascular thrombosis is postulated to cause or to contribute to the development of uncharacterized ("primary") pulmonary hypertension (PPH). To assess whether there is ongoing platelet-fibrin thrombosis in patients with PPH, we measured specific markers of platelet activation: platelet factor 4 (PF4) and beta-thromboglobulin (BTG); of fibrin formation: fibrinopeptide A (FPA); and of fibrin dissolution: fibrinopeptide BB1-42 (FPBB1-42) in peripheral venous blood from 10 patients with PPH (group 2). Results were compared with those of normal volunteers (group 1, n = 9) and with results from patients with pulmonary hypertension secondary to congenital heart disease (group 3, n = 7). Both groups 2 and 3 exhibited severe pulmonary hypertension (mean pulmonary arterial pressure = 62 +/- 20 mm Hg and 70 +/- 13 mm Hg, respectively). Mean level of PF4, BTG, FPA, and FPBB1-42 in patients with pulmonary hypertension, either primary or secondary to congenital heart disease, did not differ from levels in normal subjects. Within group 2, levels of platelet proteins and fibrinopeptides did not differ between patients who were classified clinically as having plexogenic arteriopathy vs thromboembolic disease. These observations suggest that a sustained state of abnormal platelet activation and fibrin formation or dissolution is not present in patients with established pulmonary hypertension.

Topics: Adult; beta-Thromboglobulin; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Hypertension, Pulmonary; Male; Middle Aged; Peptide Fragments; Platelet Activation; Platelet Factor 4

A kindred with a familial hemoglobinopathy and familial primary pulmonary hypertension with autosomal dominant transmission has been identified. Affected family members were obvious from their cyanosis due to a reduced affinity for oxygen by the hemoglobin variant. The mother and one child had clinical pulmonary hypertension, whereas two siblings had cyanosis and preclinical pulmonary vascular disease as evidenced by abnormal perfusion lung scans and elevated levels of fibrinopeptide A in the face of normal pulmonary hemodynamics. In one, pulmonary hypertension could be induced with exercise. The studies on this family support the hypothesis that primary pulmonary hypertension may be initiated by abnormalities of the pulmonary vascular bed that predispose to in situ thrombosis. The possible common genetic transmission of the two diseases offers the speculation that the gene that confers predisposition to pulmonary hypertension may be located near the gene responsible for beta globulin.

Topics: Beta-Globulins; Female; Fibrinopeptide A; Genes, Dominant; Hemoglobinopathies; Hemoglobins, Abnormal; Humans; Hypertension, Pulmonary; Middle Aged

A case of thromboembolic pulmonary hypertension associated with long-standing thrombocytosis is presented. In this patient we found a significant local pulmonary platelet activation and thrombin generation as indicated by the existence of a transpulmonary gradient for thromboxane A2, beta thromboglobulin and fibrinopeptide A. Prolonged heparin and acetylsalicylic acid treatment resulted in improvement of clinical and hemodynamic conditions. These findings support the usefulness of anticoagulating and antiaggregating therapy in selected cases of pulmonary hypertension.

Topics: Adult; Aspirin; beta-Thromboglobulin; Fibrinopeptide A; Heparin; Humans; Hypertension, Pulmonary; Male; Platelet Activation; Splenectomy; Thalassemia; Thrombocytosis; Thromboxane A2; Time Factors

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.

Topics: Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Humans; Hypertension, Pulmonary; Lung Diseases; Plasminogen Inactivators; Prospective Studies; Thrombosis