Asunto(s)
Algoritmos , Deficiencia del Factor XIII/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Plaquetas/química , Consanguinidad , Exones/genética , Factor XIII/análisis , Factor XIII/genética , Factor XIII/inmunología , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/epidemiología , Deficiencia del Factor XIII/genética , Pruebas Hematológicas/economía , Humanos , Incidencia , Irán/epidemiología , Mutación Missense , Mutación Puntual , Reacción en Cadena de la Polimerasa/economía , Subunidades de Proteína/genética , SolubilidadRESUMEN
PURPOSE OF REVIEW: Here we review recent developments concerning the diagnosis, classification and treatment of factor XIII (FXIII) deficiency and new findings related to the pathogenesis of the disease. RECENT FINDINGS: Most recently, the International Society on Thrombosis and Haemostasis, Scientific and Standardization Committee published a guideline for the diagnosis and classification of FXIII deficiencies. Since 2009, three novel mutations causing severe bleeding diathesis were discovered in the FXIII-A gene and one in the FXIII-B gene. A newly described FXIII-A deficiency was of the extremely rare qualitative type II deficiency. The first well established founder effect was reported for a causative FXIII-A mutation. More than a quarter of all FXIII-A deficiencies are due to autoantibody, among them the first case of deficiency caused by anti-FXIII-B autoantibody was reported in the last 2 years. The safety and effectiveness of plasma FXIII concentrate for prophylaxis and treatment is now well established. The new recombinant FXIII product is currently in phase III clinical trial and the preliminary data are promising. SUMMARY: FXIII deficiency is considered the most underdiagnosed bleeding diathesis. The recommended algorithm for its diagnosis and classification could improve the diagnostic efficiency. The preferred choice for substitution therapy is FXIII concentrate (plasma-derived or, in the future, recombinant).
Asunto(s)
Deficiencia del Factor XIII , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/diagnóstico , Deficiencia del Factor XIII/terapia , HumanosAsunto(s)
Coagulación Sanguínea , Deficiencia del Factor XIII/diagnóstico , Factor XIII/análisis , Algoritmos , Autoanticuerpos/sangre , Biomarcadores/sangre , Coagulación Sanguínea/genética , Pruebas de Coagulación Sanguínea/normas , Análisis Mutacional de ADN/normas , Electroforesis en Gel de Poliacrilamida/normas , Factor XIII/genética , Factor XIII/inmunología , Deficiencia del Factor XIII/sangre , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/genética , Deficiencia del Factor XIII/inmunología , Fibrina/metabolismo , Predisposición Genética a la Enfermedad , Humanos , Valor Predictivo de las PruebasAsunto(s)
Deficiencia del Factor XIII , Factor XIII , Transglutaminasas/deficiencia , Secuencia de Aminoácidos , Diagnóstico Diferencial , Factor XIII/química , Factor XIII/genética , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/etiología , Genes Recesivos , Humanos , Datos de Secuencia Molecular , Transglutaminasas/genéticaRESUMEN
Factor XIII consists of two catalytic a and two noncatalytic b subunits. The gene for the a subunit is located on chromosome 6, the gene for the b subunit on chromosome 1. Both genes have been characterized. There are several different allelic forms of the a subunit in the normal population and some microheterogeneity for the b subunit. Most patients with congenital factor XIII deficiency lack the a subunit in plasma; few patients appear to have a complete lack of the b subunit. The genes from patients with factor XIII deficiencies were obtained and examined. Based on these analyses a new genetic classification for factor XIII deficiency is proposed: a deficiency of the a subunit (formerly termed type II), a deficiency of the b subunit (formerly known as type I), and a possible combined deficiency of both a and b subunits.
Asunto(s)
Deficiencia del Factor XIII/genética , Factor XIII/genética , Secuencia de Aminoácidos , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 6/genética , Factor XIII/química , Deficiencia del Factor XIII/clasificación , Femenino , Genes , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Mutación Puntual , Polimorfismo Genético , Conformación Proteica , Empalme del ARNRESUMEN
A questionnaire was sent out in 1993 to more than 350 European institutions caring for patients with hemorrhagic disorders with the request to provide data of patients with congenital factor XIII deficiency, to pursue the following aims: (1) establish a registry of congenital factor XIII deficiency patients, (2) promote exchange between clinicians and basic researchers, (3) improve diagnostic and therapeutic approaches, and (4) stimulate research on gene defects and their impact on factor XIII function. So far, 72 patient questionnaires from 60 families have been collected. Their bleeding pattern is typical, with frequent involvement of the umbilical cord and the central nervous system. Forty-nine patients receive regular factor XIII replacement, but obviously some patients with mild symptoms do not require prophylactic substitution, despite low factor XIII levels. On the other hand, 18 patients had factor XIII activities of > or = 5% of normal, but only 3 of those patients were reported to have no bleeding symptoms. Furthermore, 17 symptomatic, apparently heterozygous relatives in eight families were observed. Seven out of 30 females aged over 18 years had experienced spontaneous abortions; wound healing problems were seen in 26 patients. Currently, a second questionnaire is being distributed to obtain more detailed information on bleeding and other symptoms, diagnostic approaches, and exclusion of concurrent other bleeding diatheses. Future activities will be validation and standardization of assays, and study of gene defects and their impact on the structure of factor XIII and symptoms of patients. We intend to expand the survey to countries outside Europe.
Asunto(s)
Deficiencia del Factor XIII , Encuestas y Cuestionarios , Aborto Habitual/etiología , Adulto , Europa (Continente)/epidemiología , Factor XIII/análisis , Factor XIII/genética , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/congénito , Deficiencia del Factor XIII/diagnóstico , Deficiencia del Factor XIII/epidemiología , Deficiencia del Factor XIII/genética , Femenino , Genotipo , Hemorragia/etiología , Humanos , Recién Nacido , Masculino , Fenotipo , Embarazo , Complicaciones Hematológicas del Embarazo/etiología , Índice de Severidad de la Enfermedad , Cicatrización de Heridas/genéticaRESUMEN
Coagulation factor XIII (FXIII) is of paramount importance in the process of fibrin stabilization, which is the final step of the coagulation cascade. The clinical significance of defective fibrin stabilization is highlighted by the severe hemorrhagic manifestations of congenital FXIII deficiency. In this paper we review the pathophysiology, clinical presentation and therapy of acquired plasma FXIII deficiencies, caused by specific inhibitors or associated with other clinical conditions. For acquired severe FXIII deficiency caused by factor-specific inhibitors, the need for prompt diagnosis and treatment is emphasized by the high hemorrhagic risk and mortality. For moderate reduction of FXIII secondary to other conditions, we discuss the relative importance of FXIII reduction in the development of clinical symptoms and the role of substitution treatment.
Asunto(s)
Deficiencia del Factor XIII , Factor XIII/fisiología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Niño , Reacciones Cruzadas , Activación Enzimática , Factor XIII/antagonistas & inhibidores , Factor XIII/inmunología , Factor XIII/uso terapéutico , Deficiencia del Factor XIII/inducido químicamente , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/inmunología , Deficiencia del Factor XIII/terapia , Femenino , Fibrina/metabolismo , Trastornos Hemorrágicos/etiología , Humanos , Inmunoglobulina G/inmunología , Enfermedades Inflamatorias del Intestino/complicaciones , Isoniazida/efectos adversos , Isoniazida/inmunología , Leucemia/complicaciones , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Trombina/metabolismoRESUMEN
In this study we present a new case of Factor XIII deficiency. The proposita, a 34 year old woman, showed a deficiency of both subunit a and subunit b, and a moderate bleeding tendency. Because of the concomitant decrease of subunits a and b the proposita is considered to be an example of Type I disease. Factor XIII levels were less than 10% both as activity and antigen. Several family members showed intermediate levels of both subunit a and b and were asymptomatic. They were considered to be heterozygotes. The hereditary pattern is autosomal incompletely recessive. Type I disease appears much less frequent than Type II.
Asunto(s)
Deficiencia del Factor XIII , Deficiencia del Factor XIII/congénito , Adulto , Factor XIII , Deficiencia del Factor XIII/sangre , Deficiencia del Factor XIII/clasificación , Deficiencia del Factor XIII/genética , Femenino , Heterocigoto , Humanos , Inmunoensayo , Linaje , Tromboelastografía , TransglutaminasasRESUMEN
Immunological and immunofluorescent studies carried out on plasma and platelets of three cases of congenital factor XIII deficiency are reported. Two of these patients were originally thought to have normal factor XIII subunit S and no subunit A. However, repeated assays carried out using different lots of antiserum showed that in reality the patients lacked both subunit S and subunit A. The false positive finding was due to the presence of a anti-factor VIII contaminant in the antiserum originally used. The third patient had a normal subunit S and no subunit A. No factor XIII antigen was found by the indirect immunofluorescent technique in normal, factor XIII deficiency and von Willebrand's disease platelets. On the contrary, by using the non-monospecific antiserum a fluorescent pattern similar to that observed by using an anti-factor VIII antiserum, had been noted. On the basis of the data presented in this paper a tentative classification of factor XIII deficiency in two groups is proposed: Type I is characterized by the lack of both factor XIII subunit S and A. Type II is characterized by a normal subunit S and no subunit A. The need for a re-evaluation of published case of factor XIII deficiency by means of monospecific antisera is indicated.