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)

Proteolytic activity was studied in platelet concentrates (PC) stored in plasma at 22 degrees C. In experiment 1, two PC with a higher (A) and a lower (B) white cell concentration were prepared from each of nine donors by centrifugation. Aliquots of the cell-free plasma, PPP, were stored as a control. Samples for the assay of fibrinopeptide A (FPA), elastase, spontaneous proteolytic activity (SPA), kallikrein-inhibiting activity, thrombin-antithrombin complexes (TAT) and D-dimers were collected initially and on days 1, 3, 5 and 7 of storage. Consumption of glucose, pH and concentrations of lactate dehydrogenase (LDH) and ATP were determined to investigate the metabolic status of the PC. The decrease in pH correlated to the leucocyte count, r = -0.74, P < 0.001 and to the increase in LDH, r = -0.74, P < 0.01. The levels of elastase and the SPA were consistently low in the PPP bags. In the PC elastase had increased by day 5 and the SPA by day 3; the levels in PC A were significantly higher than in PC B, P < 0.01. The leucocyte count correlated with the elastase activity, r = 0.71, P < 0.01, and with the SPA, r = 0.65, P < 0.01. A minor increase in FPA was demonstrated while no TAT and D-dimers could be detected. The cause of the formation of FPA was studied in experiment 2; three bags of PC and four of PPP were prepared from each of 16 donors. To the PC and three of the PPP bags either hirudin, aprotinin or no enzyme inhibitor (control) was added.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteolytic activity during storage of platelets in plasma. 130 10

The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.
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PMID:Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease. 151 8

In a preliminary report from the Caerphilly study four haemostatic factors showed univariate associations with prevalent ischaemic heart disease after adjusting for age. These factors were fibrinogen concentration, plasma viscosity, white cell count, and the heparin-thrombin clotting time. Age and these haemostatic variables were entered into a stepwise multiple logistic regression analysis; after age the white cell count and heparin-thrombin clotting time remained significantly associated with ischaemic heart disease. Further regression analyses indicated that diastolic blood pressure contributed additionally to this association with ischaemic heart disease but that smoking habit did not.
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PMID:Haemostatic factors and ischaemic heart disease. The Caerphilly study. 399 61

Methods have been developed to isolate human platelet membrane fragments from plasma and serum. Rabbit antibody produced against the human platelet membrane glycoprotein complex, IIb/IIIa, was utilized in an immunoelectrophoretic assay to evaluate the amount of this antigen in various microparticle preparations. The serum concentration of platelet microparticles was more than tenfold greater than that observed for plasma (65 micrograms/ml versus 4.4 micrograms/ml, respectively). Ultrastructural evaluation of either plasma or serum-derived microparticles disclosed a variety of membrane fragments and membrane-bound vesicles with occasional fragments of red blood cells, white blood cells, and platelets. In contrast, microparticle preparations derived from isolated washed platelets after thrombin stimulation contained a heterogeneous array of membrane fragments, vesicles, and granules but no identifiable red cell, white cell, or platelet fragments. Thus, these studies demonstrate that normal human plasma and serum contain platelet membrane fragments that are produced during cell activation. If a similar loss of platelet membranes occurs in vivo following reversible platelet activation, it is possible that the resulting membrane modifications may be of importance in both the structural and functional changes that develop during platelet senescence.
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PMID:Isolation of human platelet membrane microparticles from plasma and serum. 711 53

The influence of haemoperfusion on blood-coagulation and cellular constituents of the blood was studied in three groups of patients. In four patients haemoperfusion was performed using a column containing acrylic-hydrogel coated activated charcoal (Haemocol), in five patients with a column containing uncoated XAD-4 nonionic polystyrene resin (Amberlite) and in five patients with a column containing cellulose coated activated charcoal (Gambro Adsorba 300 C). Perfusion was performed during 4 h with a flow of 300 ml/min. Before the start, 2 h after the start, at the end and 2 h after the end of the perfusion the haemoglobin concentration, haematocrit, leucocyte number, differential white cell count, thrombocyte number and heparin concentration were measured. Before the start and 2 h after the end prothrombin time, thrombin time, partial thromboplastin time, reptilase time, fibrinogen, prothrombin, factors V, VII, X, antithrombin III, bleeding time (Ivy), ethanol gelation test, fibrin split products and plasminogen were measured. The following conclusions can be drawn: haemoperfusion per se causes haemodilution; polystyrene resin causes in some patients a temporary reduction of the leucocyte number during haemoperfusion; polystyrene resin causes a significant reduction of thrombocyte number compared to coated activated charcoal; polystyrene resin and to a lesser extent acrylic-hydrogel-coated activated charcoal causes in some patients a prolongation of bleeding time probably by inducing alteration of thrombocyte function caused by release; polystyrene resin and probably also acrylic-hydrogel-coated activated charcoal causes an increased fibrinolytic activity without signs of disseminated intravascular coagulation.
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PMID:The influence of haemoperfusion on haemostasis and cellular constituents of the blood in the treatment of intoxications: a comparative study of three types of columns (Haemocol, Amberlite XAD-4, Gambro Adsorba 300 C). 727 53

A disturbing interaction of PAN membranes and the bradykinin generation system particularly in the presence of angiotensin converting enzyme inhibitors has been described. A modified new membrane, SPAN (special PAN), was produced by varying the polymer components in type and composition, in particular by a reduction in Na-Methallylsulfonate. Although the SPAN membrane successfully averted the bradykinin generating ability of PAN, it was important to determine whether such a modification did not lead to a loss of the satisfactory biocompatibility profile characteristic of the parent membrane. For this purpose, we conducted the present clinical study in nine patients comparing 3 membranes; (i) a polysulphone membrane (F60S); (ii) PAN; and (iii) SPAN, to examine the clinical biocompatibility profile and performance of the new membrane. A small increase in C5a with F60S and SPAN was found which is in the range expected for highly biocompatible synthetic membranes. The three dialysers had a similar inert profile for terminal complement complex arterial values, and had similar venous values. A minimal nonsignificant decline in white cell count was observed at 15 min for all dialysers, but otherwise WBC counts were unchanged. Platelet counts were unchanged throughout treatment for the three dialysers. Arterial and venous thrombin-anti-thrombin complex values were similar for all three dialysers. F60S and SPAN dialysers had similar urea clearances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthetic modification of PAN membrane: biocompatibility and functional characterization. 749 15

In septic patients capable of normal white cell responses, high plasma levels of PAI-I, t-PA antigen and t-PA-PAI-I complex were observed. The ratios of t-PA and PAI-I were such that free PA activity was almost never observed. In patients severely leucopenic prior to becoming septic the changes were significantly less marked, so presence of leucocytes enhances the fibrinolytic inhibition occurring in sepsis. The non-leucopenic septic group showed greater evidence of thrombin generation in that FPA levels were higher but fibrinogen levels were only slightly less and antithrombin levels not different from those in the leucopenic group. A greater tendency to fibrin deposition and the striking fibrinolytic inhibition noted in patients with normal white cell responses may contribute to the development of some of the complications of sepsis in which fibrin deposition participates and may explain their relative rarity in leucopenic patients. When shock supervened, levels of PAI-I were high in both leucopenic and non-leucopenic groups, indicating that a source of PAI-I outwith the leucocytes themselves contributes to the phenomena observed.
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PMID:Influence of white blood cells on the fibrinolytic response to sepsis: studies of septic patients with or without severe leucopenia. 764 91

Ancrod, a thrombin-like enzyme purified from the venom of Calloselasma rhodostoma, was administered to rabbits intravenously, and blood samples were obtained at 1, 3, 6, 10, and 24 hours after infusion. Ancrod caused a rapid and sustained defibrinogenation within the first 6 hours, with production of fibrinogen degradation products (FDPs) peaking at 1 hour and declining to background level at 6 hours. No significant changes in platelet count, white cell count, or hematocrit was observed. Citrated PRP prepared 1, 3, and 6 hours after ancrod infusion showed diminished aggregation, adenosine triphosphate (ATP) release, and thromboxane B2 formation on the addition of collagen. Although platelet suspension prepared from defibrinogenated platelet-rich plasma (PRP) at 3 hours showed no significant change in aggregation and ATP-releasing activity, the latent period of platelet aggregation was prolonged. When the remaining platelet-poor plasma obtained from defibrinogenated PRP at 3 hours was used to suspend the normal washed platelets prepared from PRP before ancrod infusion, the platelets showed a similar defect in aggregation and release action. Addition of fibrinogen (200 micrograms/ml to 2 mg/ml) to the above preparation partially restored aggregation but not capacity for secretion and thromboxane formation. When normal washed platelets were suspended with the defibrinogenated plasma, prepared by mixing ancrod with normal plasma in vitro and removing the formed fibrin, the platelet suspension showed impaired platelet aggregability, and the aggregability could be restored to the normal level by the addition of exogenous fibrinogen to this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antiplatelet activity of ancrod on administration to rabbits. 770 7

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.
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PMID:Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. 988 16

The extensive area of contact between blood and synthetic surfaces during cardiopulmonary bypass results in the activation of the kallikrein, the complement and the clotting and fibrinolytic systems. This results in white cell activation and a whole body inflammatory response. Pulmonary neutrophil sequestration is also known to occur during cardiopulmonary bypass and has been associated with pulmonary damage. This has been previously demonstrated using the technique of differential neutrophil counts in simultaneous venous and left atrial samples. The efficacy of retinal fluorescein angiography as an indicator of cerebral microembolism has also been proved in previous studies. The objectives of this study were to determine whether heparin precoating with Duraflo II reduced pulmonary neutrophil sequestration, retinal microembolism and postoperative blood loss. Fourteen patients were randomized into two groups using either heparin-coated or nonheparin-coated cardiopulmonary bypass circuits. The preliminary results suggest a reduction in pulmonary neutrophil sequestration (p greater than 0.05) and the generation of thrombin antithrombin complexes (p less than 0.05). Retinal microembolism was not significantly different in the two groups nor was the postoperative blood loss. Thus, heparin-coated cardiopulmonary bypass circuits do not reduce pulmonary neutrophil sequestration, retinal microembolism or postoperative blood loss.
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PMID:Clinical experience with heparin-coated cardiopulmonary bypass circuits. 1014 10


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