ABSTRACT
Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.
Subject(s)
Factor VII Deficiency/complications , Factor VII Deficiency/diagnosis , Thrombosis/complications , Adolescent , Adult , Amino Acid Substitution , Exons , Factor VII/genetics , Factor VII/metabolism , Factor VII Deficiency/genetics , Female , Genotype , Humans , Male , Middle Aged , Mutation , Thrombosis/diagnosis , Thrombosis/etiology , Young AdultABSTRACT
The reagents most frequently used for FVII activity assay are obtained by rabbit brain or human placenta. In recent years, human recombinant thromboplastins have received great attention. FVII activity in FVII deficiency is usually low, regardless of the thromboplastin used. There are a few exceptions to this rule. These are represented by FVII Padua (Arg304Gln), FVII Nagoya (Arg304Trp), and FVII (Arg79Gln). In these three instances, clear discrepancies were noted in the FVII activity depending on the thromboplastin used. This indicates that at least two areas of FVII are involved in tissue binding, namely an epidermal growth factor domain of the light chain (Arg79Gln) and the catalytic domain (Arg304), controlled by exons 4 and 8, respectively. Since these three variants are cross reactive material positive, namely they are Type 2 defects, all other variants with normal antigen should be investigated by a panel of at least three tissue thromboplastins (rabbit brain, human tissue or human recombinant, and ox brain derived) in order to obtain a satisfactory classification.
Subject(s)
Factor VII Deficiency/drug therapy , Factor VII Deficiency/genetics , Factor VII/genetics , Homozygote , Thromboplastin/therapeutic use , Animals , Factor VII/metabolism , Humans , Rabbits , Treatment OutcomeABSTRACT
Congenital FVII deficiency is usually subdivided into two forms: type I and type II. Type I is characterized by a concomitant deficiency of FVII activity and FVII antigen (true deficiency). Type II is characterized by a discrepancy between FVII activity which is always low and FVII antigen which may be normal, near normal, or reduced. Thromboplastins of different origins may show a discrepant behaviour towards type II FVII deficiencies. The abnormal factor VII present in these forms may, in fact show, different levels of activity, according to the thromboplastin used in the assay system. Typical of these variants is the Arg304Gln mutation (know as FVII Padua). In this variant, FVII level is low when rabbit brain thromboplastin is used, whereas the level is perfectly normal when ox-brain thromboplastin is employed. Intermediate levels are obtained if human placenta or human recombinant is used. Since ox-brain thromboplastin is very sensitive to activated FVII, the normal FVII levels obtained in FVII Padua could be due to abnormally high circulating levels of activated FVII. The purpose of the present paper was to investigate the level of activated FVII present in homozygotes and heterozygotes with FVII Padua. For comparison, a group of patients with type I or 'true' deficiency was also investigated. A group of 21 normal patients served as controls. The activated FVII level found in FVII Padua was 8·4 and 41·0 mU/ml for homozygotes and heterozygotes, respectively. The level found in homozygous true deficiency was unassayable, whereas that found in heterozygotes was 36·2 mU/ml. The level found in the control population was 64·9 mU/ml in agreement with other reports. The low levels of activated FVIIa found in homozygotes with FVII Padua indicate that the normal FVII activity found with ox-brain thromboplastin cannot be attributed to higher than normal circulating levels of FVIIa.
Subject(s)
Factor VII Deficiency/genetics , Factor VII Deficiency/metabolism , Factor VII/metabolism , Factor VIIa/metabolism , Heterozygote , Homozygote , Adult , Blood Coagulation Tests , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Patients with the Arg304Gln mutation in factor VII Padua (FVII Padua) show discrepant activity levels that depend on the thromboplastin used in the assay system. This report investigates the possibility that residues close to Arg304 (exon 8) show the same discrepant behavior. All available homozygous patients with a mutation in a 13-residue region (preceding and following Arg304) have been evaluated. Only the Arg304Trp mutation showed a discrepancy similar to that shown by the Arg304Gln mutation. Other homozygotes failed to show differences, despite their all being positive for cross-reacting material. Another FVII amino acid residue involved in tissue factor binding and activation is Arg79 (exon 4). No comparison could be carried out because no homozygotes for deficiency in this region have ever been described. The relationship between these 2 residues involved in tissue factor binding and activation has not yet been completely clarified; however, Arg residues 79 and 304 are the only 2 residues definitely shown thus far to be involved in this important function.
Subject(s)
Catalytic Domain/genetics , Factor VII Deficiency/genetics , Factor VII , Adolescent , Adult , Amino Acid Sequence , Amino Acid Substitution , Animals , Arginine/metabolism , Cattle , Exons , Factor VII/chemistry , Factor VII/genetics , Factor VII/metabolism , Female , Genotype , Heterozygote , Homozygote , Humans , Male , Middle Aged , Mutation , Phenotype , Rabbits , Thromboplastin/metabolismABSTRACT
Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis.
Subject(s)
Coagulation Protein Disorders/epidemiology , Thrombosis/epidemiology , Adult , Aged , Case-Control Studies , Coagulation Protein Disorders/complications , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Thrombosis/etiologyABSTRACT
Factor VII (FVII) deficiency, the most frequent defect among the rare bleeding disorders, is commonly divided into type I and type II. In the former, there is a concomitant decrease in FVII activity and antigen. In the latter, there is a clear discrepancy between activity which is low and antigen which is normal or nearly normal. FVII Padua (Arg304Gln) is characterized by different reactivity towards different tissue thromboplastins. FVII levels were assayed by the use of different tissue thromboplastins, namely rabbit brain, human placenta, human recombinant and ox brain thromboplastin, in 6 homozygous patients. Cases reported in the literature were also evaluated. Ox brain thromboplastins yielded normal values, whereas human tissue or recombinant human thromboplastins yielded only slightly higher levels of activity than those obtained with rabbit brain reagents. The ox brain versus rabbit brain ratio was about 22, whereas the ratio for human placenta or human recombinant versus rabbit brain thromboplastin was only about 5. The FVII antigen versus rabbit brain, human tissue and ox brain activity ratios were 24.8, 4.3 and 1.1, respectively. These results indicate that the ox brain versus the rabbit brain thromboplastin ratio supplies a wider difference than the one between human tissue and rabbit brain. The antigen/ox brain activity ratio of 1.1 fully confirms this assertion.
Subject(s)
Brain Chemistry/genetics , Factor VII/genetics , Thromboplastin , Amino Acid Substitution , Animals , Arginine/genetics , Cattle , Factor VII/metabolism , Glutamine/genetics , Homozygote , Humans , RabbitsABSTRACT
O objetivo deste trabalho foi testar a funcionalidade do sisema de suporte de peso corporal (SPC) instrumentalizado e medir a quantidade de suporte de peso durante o treino demarcha em esteira. Metodo: no SPC instrumentalizado foram inseridas duas celulas de carga, uma tipo anel para meditacao da forca vertical e outra tipo viga retangular para medicao de carga no suporte manual. Somando-se as forcas das celulas tem-se a carga total do SPC durante a marcha. Para testar a funcionalidade do sistema foi realizado ensaio com um paciente com paralisia cerebral dplegica. Resultados: este paciente que possuia autonomia de 33 passos sem apoio conseguiu realizar o ensaio nas velocidades de 1,0 KM/h a 3,5km/h, caminhando por 10 min. Foi conseguida a mensuracao da quantidade de peso suportada pelo instrumental durante todo o ensaio. Com base nas aquisicoes, pode-se ver que o porcentual suportado esta continuamente variando com a locomocao do paciente. A utilizacao do SPC instrumentalizado durante o treino de marcha gerou algumas vantagens: saber o valor e a variacao da porcentagem de peso, gerar retroalimentacao para o paciente e armazenar dados para o acompanhamento do paciente e de sua evolucao ou para compara-lo aos outros pacientes. Conclusao: o equipamento desenvolvido funcionou eficazmente e foi possivel mensurar a forca durante a marcha com SPC na esteira. Ficou caracterizado que esta forca nao e constante e varia tambem com o aumento da velocidade da marcha
Subject(s)
Body Weight , Exercise Test , GaitABSTRACT
Os autores expoem a tecnica da transposicao dos retalhos de Machek-Blaskovies e concluem, pelos bons resultados obtidos, ser talvez, esta, a melhor solucao para a triquiase total
