Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. 239 5

Primary pulmonary hypertension (PPH) is a rare disorder, usually fatal. Although the cause of the disease is unknown, the vascular endothelium seems to play a key role. It has been proposed that a vascular endothelial dysfunction would provoke pulmonary vasoconstriction, platelet activation and thrombin formation; some of these events have already been proven. The presence of thrombosis in PPH patients has been demonstrated, and it seems to have a relationship with a vascular endothelium-dependent coagulation abnormality. Substances of endothelial cell origin capable of modifying the coagulation mechanisms are: heparan-sulfate, thrombomodulin, protein S, tissue factor pathway inhibitor (TFPI), tissue factor, von Willebrand factor, prostacyclin and endothelial-derived relaxing factor; functional and multimeric-pattern alterations in von Willebrand factor have already been reported in PPH patients.
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PMID:[Hemostatic system factors and endothelial function in primary pulmonary hypertension]. 783 24

Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases. Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension. These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.
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PMID:The role of thrombosis in severe pulmonary hypertension. 877 77

The aim of the study was elucidation of hemostatic effects of low-molecular heparin Flaxiparin in patients with primary pulmonary hypertension (PPH). 10 PPH patients (mean age 39.0 (+)- 3.2 years, mean history of the disease 5.1 (+)- 0.9 years) were treated up to 6 months. For the first month Flaxiparin was injected in therapeutic doses 15,000 AXa ICU, twice a day. The next 5 months prophylactic doses were administered twice a day (7,500 AXa ICU). D-dimer, fragment 1 + 2, complex thrombin-antithrombin, beta-thromboglobulin, protein C, antithrombin III, antigen of tissue plasminogen activator and inhibitor of tissue plasminogen activator of type I, activity of the latter were measured before the treatment, after the therapeutic and prophylactic courses, 6 months after the treatment. Initially, the patients had procoagulative hemostatic disorders. i.e. activation of blood coagulation; fibrinolytic system was also affected. In the course of Flaxiparin therapy blood coagulation and fibrinolysis improved significantly. However, the effect was not persistent after the drug discontinuation. Flaxiparin can be recommended for treatment of PPH.
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PMID:[The effect of long-term Fraxiparin treatment on hemostasis in patients with primary pulmonary hypertension]. 941 32

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.
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PMID:Plasma coagulation profiles in patients with severe primary pulmonary hypertension. 987 7

Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.
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PMID:Impairment of the plasmin activation system in primary pulmonary hypertension: evidence for gender differences. 1152 3