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)

The following clinical groups of volunteers were studied: patients long after recovery from myocardial infarction (MI), others after recovery from deep vein thrombosis (DVT), patients with intermittent claudication, with diabetes, and male and female controls who were well matched. All were subjected to many platelet and clotting tests together with clinical, biochemical and haematological measurements in an attempt to find long term abnormalities in these various diseases. The male MIs differed very significantly from the controls in having much more heparin neutralizing activity (P less than 0.001)and less anti-thrombin (P less than 0.01). Less significantly, some bleeding time tests indicated less bleeding and the patients' platelets were larger. The females with MI had in general the same abnormalities but to a lesser degree. The patients with intermittent claudication, none of whom had a history of MI, had almost the same abnormalities and to the same degree. In deep vein thrombosis the heparin neutralizing activity was also clearly increased; the other tests were generally in the same direction but many were not significant. The diabetics had shorter bleeding times but little else abnormal relative to the controls, suggesting a different pathological process. When all male patients and controls were "scored" according to the degree of atherosclerosis there was a close overall correlation between the degree of atherosclerosis and the increase in the HNA level (r = --0.50, n = 66, P less than 0.001) and the decreased anti-thrombin (r = 0.25, n = 66, P less than 0.05).
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PMID:Blood changes in atherosclerosis and long after myocardial infarction and venous thrombosis. 5 92

Ticlopidine is an inhibitor of platelet action that has been used in the treatment of a variety of disease states in which platelets play a prominent role. Studies in animals and man have demonstrated that ticlopidine is a potent inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), and variably inhibits aggregation due to collagen, adrenaline (epinephrine), arachidonic acid, thrombin, and platelet activating factor. Inhibition of platelet aggregation is both dose- and time-related, with its onset of activity being 24 to 48 hours, its maximal activity occurring after 3 to 5 days, and its activity still being present 72 hours after a final dose. Ticlopidine also inhibits the release reaction of platelets, prolongs bleeding time, reduces plasma levels of platelet factor 4 and beta-thromboglobulin in patients in whom these proteins are elevated, and may also inhibit platelet adhesion, increase red cell filtrability and decrease whole blood viscosity. In a large number of animal models, ticlopidine markedly inhibits thrombus formation or graft occlusion. Ticlopidine is well absorbed after oral administration. It is extensively metabolised and at least one of its metabolites is pharmacologically active. Therapeutic trials in patients with chronic arterial occlusion due to thrombangitis obliterans or arteriosclerosis obliterans, post-myocardial infarction, cerebrovascular thromboembolic disease, subarachnoid haemorrhage, vascular shunts or fistulas for haemodialysis, and sickle cell disease have shown promise for the use of ticlopidine. However, trials of patients with intermittent claudication, angina pectoris, diabetes mellitus with microvascular disease, aortocoronary bypass grafts, and vascular prostheses have had conflicting results or have shown an unfavourable side effect profile. Further studies are clearly required to establish the role of ticlopidine in many of these areas, some of which are already in progress. Overall, side effects occur in 10 to 15% of patients receiving ticlopidine. The most common side effects are gastrointestinal disturbances and skin rashes. Neither of these necessarily require discontinuation of therapy in most patients. Agranulocytosis, thrombocytopenia, and cholestatic jaundice have also been reported. Bleeding is infrequent except possibly in patients receiving ticlopidine prior to some surgical procedures.
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PMID:Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. 330 67

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.
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PMID:Platelets in the prediction of thrombotic risk. 715 92

In the natural history of patients with peripheral obliterative arterial disease (POAD) the prognosis of the complaint "intermittent claudication" is relatively good and the amputation rate is presently only about 3%. However, POAD patients carry a high risk of cardiovascular events and their cumultative mortality rate within 10 years is as high as 40-50%. Atherothrombotic events in the coronary and, less frequently, cerebral arteries are by far the first cause of death and disability in these patients. The rationale for antithrombotic drugs in the treatment of POAD lies in the pivotal role of platelet activation and thrombin formation in the evolution of the atherothrombotic lesions, but also in the effect of some of these drugs on the regulation of microcirculatory responses. In acute thrombotic arterial occlusion, Heparin is the "first application" drug, especially in support of interventional revascularisation procedures. Regional thrombolysis often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in revascularisation of especially infrainguinal-supra popliteal occlusions. However, controlled clinical trials are needed. In chronic POAD, intermittent claudication can be improved with a rational walking exercise programme, but, besides pentoxyphilline, especially ticlopidine significantly adds to the benefits of exercise. Regarding districtual progression of atherothrombosis and especially cardiovascular events, both aspirin and ticlopidine have been shown effective in single studies or meta-analyses. In a recent observational study of pooled data the cumulative endpoint including myocardial infarction, stroke and vascular death was reduced by 25 +/- 10% in the generality of patients treated with antiplatelet drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as Iloprost and Prostaglandin E1 favourably influence rest pain and ulcer healing, but less evidence is available on their effects on hard events as amputation and death. In conclusion, following the general indication to "be conservative" in the treatment of these patients, it seems clear that antithrombotic drugs have become by far a key medication in all different phases of POAD.
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PMID:Antithrombotic drugs in peripheral obliterative arterial diseases. 795 59

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma levels of tumor necrosis factor and endothelial response in patients with chronic arterial obstructive disease or Raynaud's phenomenon. 798 28

The authors evaluated elements of the coagulation and fibrinolytic systems in 18 male patients with intermittent claudication vs 19 men matched for risk factors who served as controls. Prothrombin time and activated partial thromboplastin time did not significantly differ in the patients and the controls. The plasminogen level in the two groups was not significantly different. The level of lipoprotein(a) was significantly higher in the patients than in the controls. The levels of antigen and the activity of protein C did not differ significantly between the two groups. The thrombomodulin level was significantly higher in the patients than in the controls. There were no significant differences between the two groups in the levels of alpha 2-macroglobulin, C1-inactivator, or antithrombin III. The levels of fibrinogen and alpha 1-antitrypsin were significantly higher in the patients vs the controls. Significantly lower levels of alpha 2-plasmin inhibitor and higher levels of alpha 2-plasmin inhibitor/plasmin complex and thrombin/antithrombin III complex were found in the patients vs the controls. These findings suggest that the levels of thrombin/antithrombin III complex, alpha 2-plasmin inhibitor/plasmin complex, and thrombomodulin may perhaps serve as indicators for injury to the peripheral endothelium and that the coagulation and fibrinolytic systems may be activated in patients with intermittent claudication.
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PMID:Evaluation of the coagulation and fibrinolytic systems in men with intermittent claudication. 867 28

The aim of this study was to examine whether there was a relationship between ultrasound-assessed morphology of the femoral artery wall and hemostatic factors, and whether these factors were associated with intermittent claudication. One hundred and thirty men at high cardiovascular risk and 51 men at low risk were examined. The subjects (high- and low-risk) with moderate/large plaque (n = 96) had higher fibrinogen, thrombin/antithrombin complex and von Willebrand factor, compared to subjects with small/no plaque. The maximum intima-media thickness of the femoral artery was significantly associated with fibrinogen. These associations were independent of current smoking habits. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex, plasminogen activator inhibitor activity, mean and maximum intima-media thickness and plaque status of the femoral artery. In conclusion, fibrinogen, von Willebrand factor and thrombin/antithrombin complex were related to plaque occurrence in the femoral artery. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex and plasminogen activator inhibitor activity.
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PMID:Femoral artery wall morphology, hemostatic factors and intermittent claudication: ultrasound study in men at high and low risk for atherosclerotic disease. 869 78

Sudden extreme physical stress is associated with an increased risk of myocardial infarction mainly in people with preexisting atherosclerosis. In this study we compared the effect of submaximal exercise on coagulation and fibrinolysis in patients with peripheral arterial occlusive disease (PAOD) with that in healthy control subjects. Fifteen PAOD) patients with intermittent claudication and 15 healthy control subjects, matched for age, sex, medication use, smoking habit, and conditioning, were studied. Thrombin-antithrombin III complex (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 antigens (Ag), t-PA activity, and plasmin-alpha2-antiplasmin complex (PAP), as well as plasma catecholamines, were measured before and after a treadmill exercise test. At rest, fibrinogen (3.3+/-0.5 versus 2.9+/-0.5 g/L [mean+/-SD]; P<.05), D-dimer (392+/-128 versus 271+/-113 ng/mL; P<.05), t-PA Ag (9.1+/-5.1 versus 5.5+/-1.2 ng/mL; P<.02), and PAI-1 Ag (14.9+/-7.1 versus 7.6+/-3.8 ng/mL; P<.002) levels in plasma were markedly higher in the patient group than in the control group. In patients but not in control subjects, exercise of similar intensity elevated circulating concentrations of TAT (from 3.43+/-1.45 to 4.83+/-2.27 ng/mL; P<.05). Exercise caused a parallel increase in D-dimer, t-PA Ag, t-PA activity, PAP, and catecholamines in both groups, whereas PAI-1 Ag remained stable. Plasma lactic acid was significantly higher in patients after exercise and was associated with lower-limb ischemia. Compared with healthy control subjects, patients with PAOD showed higher t-PA Ag, PAI-1 Ag, and D-dimer levels both at rest and after exercise. Notably, submaximal exercise on a treadmill enhanced thrombin formation in patients with PAOD but not in the control subjects. Sudden catecholamine release and local ischemia during exercise may accelerate the preexisting prothrombotic potential of the atherosclerotic vessel wall.
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PMID:Physical exertion induces thrombin formation and fibrin degradation in patients with peripheral atherosclerosis. 948 89

There is evidence that the coagulation system is activated in patients with peripheral arterial occlusive disease (PAOD). The beneficial effects of the vasoactive drug prostaglandin E1 (PGE1) may rely in part on the modulation of the coagulation system. The study was designed to evaluate the effects of PGE1 on hemostatic and fibrinolytic variables in patients with intermittent claudication. Therefore molecular markers of thrombin (prothrombin fragment 1+2, PTF 1+2; thrombin-antithrombin III complexes, TAT) and fibrin formation (fibrinopeptide A, FPA) and markers of the fibrinolytic activity (fibrin degradation products, D-dimers) were determined before and immediately after the first PGE1 dose (60 microg in 100 ml NaCl over 2 h i.v.) as well as after 4 weeks of daily infusion therapy in 12 PAOD patients and in eight control patients before and after a single placebo infusion. Plasma levels of PTF1+2, TAT, FPA and D-dimers tended to decrease after the initial dose of PGE1. Infusion therapy with PGE1 for 4 weeks led to a decrease of all hemostatic and fibrinolytic parameters with most pronounced changes for PFT1+2, D-dimers and plasminogen activator inhibitor-1 decreasing by 11% (P<0.05), 20% (P<0.05), and 7% (P<0.05), respectively. These variables remained unchanged in controls with placebo infusion. In summary, infusion therapy with PGE1 in patients with PAOD reduces thrombin formation and results in a decrease of fibrin degradation. PGE1 may thus reduce fibrin deposition involved in the pathogenesis of atherosclerosis.
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PMID:Hemostasis and fibrinolysis in patients with intermittent claudication: effects of prostaglandin E1. 1109 Feb 53

There are a limited number of clinically effective pharmacotherapeutic agents for treatment of peripheral vascular disorders. Pentoxifylline and cilostazol are available for the symptomatic treatment of intermittent claudication. Analogs of carnitine and L-arginine are being evaluated for treatment of the symptoms of intermittent claudication, and prostaglandins and growth factors are being evaluated for critical limb ischemia. Calcium channel blockers remain the treatment of choice for Raynaud's phenomenon. Alternative vasodilators may be used selectively to treat individuals with Raynaud's phenomenon who are intolerant of calcium channel blockers or in whom such therapy has been unsuccessful. Prostaglandins have been evaluated in patients with refractory Raynaud's phenomenon who also have digital ulceration. The mainstay of short-term treatment (and prophylaxis) of deep vein thrombosis (DVT) has been unfractionated heparin, but now the use of low molecular weight heparin (LMWH) has emerged. Newer agents, such as heparinoids and direct thrombin inhibitors, hold promise for the prevention and treatment of DVT. Prolonged treatment with warfarin is still required to prevent recurrent thrombosis, although the duration of treatment has come under debate.
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PMID:Drug treatment of peripheral vascular disease. 1172 42


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