No data available that match "Hypoprothrombinemias"

*  SelfDecode | Genome Analysis
Hypoprothrombinemias F2. Hypotonia-Cystinuria Syndrome PREPL. Ichthyosis Follicularis Atrichia Photophobia Syndrome MBTPS2. ...
*  SelfDecode | Genome Analysis
Hypoprothrombinemias F2. Hypothermia IL12B. Ige Responsiveness, Atopic MS4A2. Immune Complex Diseases IFNG. ...
*  List of MeSH codes (C16) - Wikipedia
... hypoprothrombinemias MeSH C16.320.099.690 --- protein c deficiency MeSH C16.320.099.820 --- thrombasthenia MeSH C16.320.099.900 ...
*  List of MeSH codes (C15) - Wikipedia
... hypoprothrombinemias MeSH C15.378.100.425.690 --- protein c deficiency MeSH C15.378.100.425.820 --- thrombasthenia MeSH C15.378 ... hypoprothrombinemias MeSH C15.378.463.735 --- platelet storage pool deficiency MeSH C15.378.463.735.400 --- hermanski-pudlak ... hypoprothrombinemias MeSH C15.378.100.141.900 --- von willebrand disease MeSH C15.378.100.220 --- disseminated intravascular ...

No data available that match "Hypoprothrombinemias"

(1/57) Simultaneous detection of FV Q506 and prothrombin 20210 A variation by allele-specific PCR.

BACKGROUND AND OBJECTIVE: Factor V Leiden is the most important risk factor for hereditary thromboembolism, whereas the mutation in the 3'-untranslated region of the prothrombin gene seems to be only a mild risk factor for thrombotic events. On the other hand the factor V mutation (Arg 506) is frequently coinherited with the prothrombin 3'-untranslated region G20210A variant and there is increasing evidence that the co-segregated prothrombin variant is an additional risk factor for venous thromboembolism, contributing to thrombotic manifestations. A rapid, simple and cost-effective screening method is, therefore, required for the detection of both factor V Leiden and the prothrombin variant A20210G. DESIGN AND METHODS: Eighty-eight patients were enrolled in this study. Forty-four had a previously identified factor V and/or prothrombin mutation, the remaining 44 patients served as negative controls. A multiplex allele specific oligonucleotide PCR was established for the simultaneous detection of the two genetic risk factors for thrombophilia. To test the specificity of the simultaneous ASO PCR approach, the mutated and physiological factor V and prothrombin amplification products were sequenced. RESULTS: The factor V Leiden mutation and the prothrombin variant were correctly identified in all of 44 patients with known mutations. Furthermore the test was able to detect the mutated factor V and the II variant alone, as well as in the cosegregated pattern. Five patients with a homozygous pattern of factor V Leiden or prothrombin variant were also correctly identified. The sensitivity of the test is therefore 100%. In none of the 44 control cases were false positive results seen. INTERPRETATION AND CONCLUSIONS: The ASO PCR test is a rapid, simple and cost-effective screening test for thrombophilia.  (+info)

(2/57) Effect of maternal anticonvulsant treatment on neonatal blood coagulation.

AIMS: To investigate the impact of maternal anticonvulsant use on the ability of cord blood to coagulate. METHODS: Cord blood prothrombin times were measured, over 15 years in a consecutive series of 137 term babies born to women taking phenobarbitone, phenytoin, and/or carbamazepine while pregnant. The response to parenteral vitamin K was measured in 83 neonates. RESULTS: Only 14 of the 105 babies born to the mothers who had therapeutic anticonvulsant blood concentrations at birth had a prolonged prothrombin time (outside the 95% reference range). None had an overt bleeding tendency. The abnormality was corrected within 2 hours by 1 mg of parenteral vitamin K, but rapid intravenous prophylaxis produced complications in three infants. CONCLUSIONS: A policy of giving vitamin K throughout the last third of pregnancy to all women being treated with anticonvulsants, as recently recommended, is not justified by the available evidence. The belief that there is a distinct, early form of neonatal vitamin K deficiency that is different from, and more dangerous than, the classic form of the disease, is not supported by a review of the published evidence.  (+info)

(3/57) Prothrombin San Antonio: a single amino acid substitution at a factor Xa activation site (Arg320 to His) results in dysprothrombinemia.

Three members of a San Antonio, Texas, family were identified with prothrombin activity levels half the normal level but to have normal levels of antigen. All exons of the prothrombin gene from the proband were sequenced. A G-to-A mutation at nucleotide 7543 was found that resulted in the substitution of His for Arg at residue 320. The Arg320-Ile321 bond is 1 of 2 sites in prothrombin cleaved by Factor Xa in the prothrombinase complex to form thrombin. Substitution of His for Arg at this site resulted in the blockage of Factor Xa cleavage, forming a dysfunctional molecule. The proband, her mother, and her maternal aunt were found to be heterozygous for this mutation. This is the first known observation of an amino acid substitution at this site that resulted in dysprothrombinemia. (Blood. 2000;95:711-714)  (+info)

(4/57) Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia.

Cephalosporin antibiotics with structures that include the heterocyclic leaving group 1-methyltetrazole-5-thiol (MTT) can cause hypoprothrombinemia and hemorrhage as a result of MTT-dependent inhibition of the gamma-carboxylation of glutamate. The structure of cefazolin also includes a heterocyclic thiol, 2-methyl-1,3,4-thiadiazole-5-thiol (MTD), and this compound can also inhibit the gamma-carboxylation of glutamate. However, unlike MTT, which is known to be present in vivo after the administration of drugs that include this structure, there have been no reports that MTD is present in vivo after cefazolin administration. We set out to determine whether MTD might be present in the tissues of patients treated with cefazolin prior to surgery. To do that, we took advantage of the fact that heterocyclic thiols can undergo S-methylation catalyzed by the genetically polymorphic drug-metabolizing enzyme thiopurine S-methyltransferase (TPMT). Initially, we tested recombinant human TPMT as a "reagent" to S-methylate MTD. MTD was a substrate for TPMT-catalyzed S-methylation, with an apparent K(m) value of 63 micro M. Recombinant TPMT, with [(14)C-methyl]S-adenosyl-L-methionine as a cosubstrate, was then used to radioactively label a methyl acceptor substrate present in liver and kidney cytosol preparations from patients who had been treated preoperatively with cefazolin. Pooled renal cytosol from 10 of those patients was used to purify and isolate the methylated product by reverse-phase high-performance liquid chromatography. That methylated compound coeluted with S-methyl MTD. When the methylated product was subjected to tandem mass spectrometry, it was identified as S-methyl MTD. Therefore, MTD is present in the tissues of patients treated with cefazolin. These observations also raise the possibility that the TPMT genetic polymorphism may represent a risk factor for cefazolin-induced hypoprothrombinemia since subjects who genetically lack TPMT would be unable to catalyze this MTD biotransformation pathway.  (+info)

(5/57) Molecular and genetic analysis of a compound heterozygote for dysprothrombinemia of prothrombin Tokushima and hypoprothrombinemia.

The molecular and genetic basis of a compound heterozygote for dys- and hypoprothrombinemia was analyzed. Abnormal nucleotide sequences of the human prothrombin gene were screened by PCR-single-strand conformation polymorphism (PCR-SSCP) with endonuclease digestion and mutated primer-mediated PCR-RFLP. A single nucleotide substitution responsible for dysprothrombinemia of prothrombin Tokushima was detected, as were three polymorphisms. The mutation for hypoprothrombinemia was detected by PCR-single-strand conformation polymorphism (PCR-SSCP) with endonuclease digestion in exon 6, near MboII-RFLP and NcoI-RFLP. Sequencing of PCR-amplified genomic DNA revealed a single base insertion of thymine (T) at position 4177. The resulting frameshift mutation caused both an altered amino acid sequence from codon 114 and a premature termination codon (i.e., TGA) at codon 174 in exon 7. Because exon 7 encodes the kringle 2 domain preceding the thrombin sequence, this frameshift leads to the null prothrombin phenotype. The inheritance of the hypoprothrombinemia gene from the father to the proband was proved by PCR-SSCP with endonuclease digestion and mutated primer-mediated PCR-RFLP.  (+info)


Serial changes in coagulation and fibrinolysis studied among 42 patients admitted to hospital with a wide variety of injuries are reported. The first hours after trauma are dominated by an acceleration of fibrinolysis (clot lysis) and clotting time which are often followed by an abrupt rebound to prolonged fibrinolysis and normal clotting. Evidence is presented that acceleration of fibrinolysis is due to flooding of the circulation by plasminogen activator and that prolongation is probably due to an inhibitor. A prolonged prothrombin time, increased prothrombin consumption index, an acceleration of the heparin-retarded clotting time, and a fall in the platelet count are also frequent during the first hours after injury. There is evidence also of an early deficiency in factor V and the onset of a fall in factor VII and prothrombin. The following days are characterized by continued prolongation of fibrinolysis, a lengthening of clotting time, and an increased prothrombin consumption index suggestive of a defect in thrombo-plastin generation. Subsequent periods of prolonged fibrinolysis may develop. Prothrombin time often continues prolonged for one to three weeks and may vary phasically; plasma prothrombin and factor VII are reduced but there is now little change in factor V. The platelet count continues to fall for one to three days, then a thrombocytosis develops, often with abnormally high platelet levels, a week or so later. Plasma fibrinogen rises within 24 hours to reach a plateau maximum a few days later and levels remain high for prolonged periods in the severely injured. Various changes are related to or influenced by the severity of trauma. Mechanisms are discussed, including thrombosis in vivo, and reference is made to homeostatic significance and its possible breakdown.  (+info)


Coagulation studies were carried out on 10 patients who bled during anticoagulant therapy, in whom no other underlying cause for bleeding could be demonstrated, and 10 patients with similar degrees of hypoprothrombinemia who were not bleeding. The average age and sex distribution of the two groups was similar, and no association was noted between the occurrence of hemorrhage and the type of anticoagulant used, the duration of treatment or the nature of the underlying disease. Comparison of the results revealed no differences in the levels of factors II, VII, IX and X or in the glass and silicone (Siliclad) clotting time, the thromboplastin generation test and Thrombotest. It was concluded that all patients on anticoagulant drugs whose prothrombin time is in the therapeutic range or longer are potential bleeders and that one cannot necessarily predict those who will bleed on the basis of coagulation studies.  (+info)

(8/57) A natural prothrombin mutant reveals an unexpected influence of A-chain structure on the activity of human alpha-thrombin.

We have recently identified in two unrelated patients with bleeding tendency a homozygous mutation causing a deletion of one of the two contiguous Lys(9)/Lys(10) residues in the A-chain of alpha-thrombin (DeltaK9). We used in vitro expression analysis to clarify the role of the deletion of Lys(9) or Lys(10) in the thrombin function. The k(cat)/K(m) value of the hydrolysis by DeltaK9 of the synthetic substrate Phe-Pip-Arg-p-nitroanilide (where Pip represents l-pipecolyl) and fibrinopeptide A was 18- and 60-fold lower, respectively, compared with wild type (WT). Interaction with antithrombin was also reduced in the mutant, the association rate being about 20-fold lower than in the WT thrombin. The sensitivity to sodium ion of DeltaK9 was found significantly attenuated compared with the WT form. DeltaK9 has a very weak platelet-activating capacity, attributed to a severely defective PAR1 interaction, whereas the binding to the platelet glycoprotein Ibalpha was unaffected. Likewise, the interaction with protein C was severely impaired, whereas interaction with thrombomodulin had a normal K(d) value. At variance with these findings, both low affinity (basic pancreatic trypsin inhibitor) and high affinity (N-alpha-[2-naphthylsulfonyl-glycyl]-4-amidinophenylalanine-piperidide) thrombin inhibitors displayed a better binding to DeltaK9 than to the WT form, indicating a better accommodation of these inhibitors into the catalytic pocket of DeltaK9. A molecular dynamics simulation of the DeltaK9 thrombin in full explicit water solvent provided support to the role of the A-chain in affecting conformation and catalytic properties of the B-chain, especially in some insertion loops of the enzyme, such as the 60-loop, as well as in the geometry of the catalytic triad residues.  (+info)

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