Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was carried out to determine whether the administration of antithrombin III decreases the risk of intraventricular hemorrhage in premature infants. In a randomized study, 60 infants born before 30 weeks of gestation were assigned to receive a loading dose of antithrombin III or placebo. There was no significant difference in the incidence of intraventricular hemorrhage between the antithrombin III and the placebo group (27.5 vs. 32%). Partial thromboplastin time, Quick's prothrombin time and platelet count were also not significantly different between the 2 groups. We conclude that the administration of antithrombin III during the first 2 days of life does not decrease incidence of intraventricular hemorrhage. Antithrombin III is a very expensive therapy and its benefits should be carefully investigated before being recommended as valuable therapy.
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PMID:Can the administration of antithrombin III decrease the risk of cerebral hemorrhage in premature infants? 1256 75

Antithrombin III (ATIII) is the main inhibitor of the coagulation proteases like factor Xa and thrombin. Anticoagulant activity of ATIII is increased by several thousand folds when activated by vascular wall heparan sulfate proteoglycans (HSPGs) and pharmaceutical heparins. ATIII isoforms in human plasma, alpha-ATIII and beta-ATIII differ in the amount of glycosylation which is the basis of differences in their heparin binding affinity and function. Crystal structures and site directed mutagenesis studies have mapped the heparin binding site in ATIII, however the hydrogen bond switch and energetics of interaction during the course of heparin dependent conformational change remains largely unclear. An analysis of heparin bound conformational states of ATIII using PEARLS software showed that in heparin bound intermediate state, Arg 47 and Arg 13 residues make hydrogen bonds with heparin but in the activated conformation Lys 11 and Lys 114 have more hydrogen bond interactions. In the protease bound-antithrombin-pentasaccharide complex Lys 114, Pro 12 and Lys 125 form important hydrogen bonding interactions. The results showed that A-helix and N-terminal end residues are more important in the initial interactions but D-helix is more important during the latter stage of conformational activation and during the process of protease inhibition. We carried out the residue wise Accessible Surface Area (ASA) analysis of alpha and beta ATIII native states and the results indicated major differences in burial of residues from Ser 112 to Ser 116 towards the N-terminal end. This region is involved in the P-helix formation on account of heparin binding. A cavity analysis showed a progressively larger cavity formation during activation in the region just adjacent to the heparin binding site towards the C-terminal end. We hypothesize that during the process of conformational change after heparin binding beta form of antithrombin has low energy barrier to form D-helix extension toward N and C-terminal end as compared to alpha isoform.
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PMID:Energetics of hydrogen bond switch, residue burial and cavity analysis reveals molecular basis of improved heparin binding to antithrombin. 2187 53

Aging is associated with increased levels of coagulation factors and decrease in natural anticoagulant factors. This strongly supports that age-related hypercoagulable state occurs in elderly. This study aimed to measure the plasma levels of coagulation factors and anticoagulant levels in young and elderly to observe the effect of age on haemostatic system. Ninety healthy individuals, both men and women were divided into two groups on the basis of age. Group I included participants of less than 40 years of age, whereas, group II comprised of participants more than 60 years of age. Fibrinogen activity was assessed by using Clauss technique. Coagulation factor VII, and factor VIII activity by corresponding one stage assay based on prothrombin time and activated partial thromboplastin time. Antithrombin III was measured by the chromogenic method. Our results showed that significantly increased levels of fibrinogen (P = 0.001) were observed in the elderly population as compared to young. Higher fibrinogen levels in younger women than men and comparatively higher level than other races was observed in our local population. Increase in factor VII levels (P = 0.05) was also observed in the elderly group. This increase was statistically significant with age in women (P = 0.03). Factor VIII rose with age in both sexes (P = 0.001). Higher antithrombin activity was observed in the younger group whereas the older group demonstrated significantly lower antithrombin activity (P = 0.001). We conclude that considerable effects of age and sex are observed on coagulation factors and naturally occurring inhibitors.
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PMID:Coagulation factors and antithrombin levels in young and elderly subjects in Pakistani population. 2313 80

Antithrombin III (AT) is the main inhibitor of blood coagulation proteases like thrombin and factor Xa. In this study we report the identification and characterization of several variants of AT for the first time in Indian population. We screened 1950 deep vein thrombosis (DVT) patients for AT activity and antigen levels. DNA sequencing was further carried out in patients with low AT activity and/or antigen levels to identify variations in the AT gene. Two families, one with type I and the other with type II AT deficiency were identified. Three members of family I showed an increase in the coagulation rates and recurrent thrombosis in this family was solely attributed to the rs2227589 polymorphism. Four members of family II spanning two generations had normal antigen levels and decreased AT activity. A novel single nucleotide insertion, g.13362_13363insA in this family in addition to g.2603T>C (p.R47C) mutation were identified. AT purified from patient's plasma on hi-trap heparin column showed a marked decrease in heparin affinity and thrombin inhibition rates. Western blot analysis showed the presence of aggregated AT. We also report a novel point mutation at position g.7549 A>G (p.T280A), that is highly conserved in serpin family. Variant protein isolated from patient plasma indicated loss of regulatory function due to in-vivo polymerization. In conclusion this is the first report of AT mutations in SERPINC1 gene in Indo-Aryan population where a novel point mutation p.T280A and a novel single nucleotide insertion g.13362_13363insA are reported in addition to known variants like p.R47C, p.C4-X and polymorphisms of rs2227598, PstI and DdeI.
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PMID:Antithrombin III deficiency in Indian patients with deep vein thrombosis: identification of first India based AT variants including a novel point mutation (T280A) that leads to aggregation. 2581 71

Thrombosis formation, restenosis, and delayed endothelium regeneration continue to be a challenge for coronary artery stent therapy. To improve the hemocompatibility of cardiovascular implants and to selectively direct vascular cell behavior, a novel heparin/poly-l-lysine microsphere was developed and immobilized on a dopamine-coated surface. We chose medical grade high nitrogen nickel-free austenitic stainless steel as the stent material since it has better biocompatibility. The stability and structural characteristics of the microspheres changed with the heparin: poly-l-lysine concentration ratio. Antithrombin III binding was significantly enhanced. Furthermore, for plasma coagulation tests, the activated partial thromboplastin time and thrombin time were prolonged and depended on the heparinfunction. The modified exhibited excellent stability and anticoagulant activity, and efficiently accelerated endothelialization and anticoagulation. This work has potential application for the design of coronary artery stent surfaces tailored for vascular cell behavior.
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PMID:Immobilization of heparin/poly-l-lysine microspheres on medical grade high nitrogen nickel-free austenitic stainless steel surface to improve the biocompatibility and suppress thrombosis. 2818 98


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