Profil épidémiologique des thrombopathies constitutionnelles dans l'ouest algérien / Epidemiological profile of constitutional thrombopathies in western Algeria

Introduction. Comme pour toutes les maladies rares ou maladies orphelines, l'étude des thrombopathies devrait être multicentrique pour recenser le maximum ou tous les patients dans une région ou dans le pays concerné. Notre étude a pour objectif d'évaluer la prévalence des thrombopathies constitutionnelles dans l'Ouest Algérien, et décrire ainsi les caractéristiques épidémiologiques de notre population. Patients et méthodes. Il s'agit d'une étude descriptive régionale du profil épidémiologique de 61 patients de l'Ouest Algérien présentant une thrombopathie constitutionnelle. Résultats. Dans notre étude a trouvé 34 thrombasthénies de Glanzmann (TG), 18thrombopathies de Jean Bernard Soulier (JBS), 08thrombopathies de May-Hegglin (MH) et un syndrome de Scott avec une prévalence globale de 1,8/1 million habitants. Conclusion. Notre travail nous a permis d'avoir un contexte global sur les thrombopathies constitutionnelles qui serait sans doute la base d'autres études de caractère clinique, biologique ou même moléculaire surtout en matière de recrutement de patients.

Introduction. As with all rare or orphan diseases, the study of inherited platelet disorders should be multicentric to identify as many or as few patients as possible in a given region or country. The aim of our study is to evaluate the prevalence of inherited platelet disorders in Western Algeria, and thus describe the epidemiological characteristics of our population. Patients and methods. This is a regional descriptive study of the epidemiological profile of 61 patients in Western Algeria with inherited platelet disorders. Results. In our study we found 34 Glanzmann thrombasthenias (TG), 18 Jean Bernard Soulier thrombopathies (JBS), 08 May-Hegglin thrombopathies (MH) and one Scott syndrome with an overall prevalence of 1.8/1 million inhabitants. Conclusion. Our work has allowed us to have a global context on inherited platelet disorders which would undoubtedly be the basis of other studies of clinical, biological or even molecular character especially in terms of patient recruitment.

Combined occurrence of Bernard-Soulier syndrome and prekallikrein deficiency

No abstract available.

Trombocitopenia familiar de plaquetas gigantes: caso clínico / Familiar Thrombocytopenia of Giant Platelets: Clinical Case

La trombocitopenia es causa frecuente de consulta en hematología pediátrica. La mayoría de veces la baja de plaquetas es por desorden de destrucción autoinmune, raramente el padecimiento tiene un comportamiento familiar-hereditario. Se presenta el caso de una paciente de 11 años de edad, conocida desde los 3 años por trombocitopenia en el rango de 50,000/mm , fue evaluada por posibilidad de desórdenes autoinmunescon estudios inmunológicos básicos: complementos, ANA, Anti ADN, factor reumatoide y los resultados fueron normales. Tratada en varias ocasiones con prednisona oral, antiRh y con inmunoglobulina intravenosa (IGIV). Se le ha brindado seguimiento prolongado por trombocitopenia que resultó ser familiar; encontrando doce afectados, que incluyen abuela materna, madre, tíos, primos y hermana. Las características clínicas y la morfología plaquetaria fueron finalmente suficientes para conducir a diagnóstico inusual: el síndrome de Bernard-Soulier (SBS). El diagnóstico fue sugerido por el frotis de sangre periférica (FSP)...

Hematological abnormalities and 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test) were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene) and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.

Management of a pregnant patient at term with Von Willebrand disease - III

Von Willebrand disease [VWD] is a common inherited bleeding disorder involving a deficiency or abnormal function of a blood clotting protein called Von Willebrand factor [VWF]. Women with VWD require monitoring during and after pregnancy. This case report describe management of a patient presenting with type III VWD at term and during labour. She had history of severe post-partum haemorrhage [PPH] after cesarean section in previous pregnancy and again had a risk of life-threatening PPH in the current gestation which was managed by appropriate planning and timely decision

Trastornos plaquetarios primarios en la especie humana, aspectos biomédicos: biología, patobiología y bioclínica / Primary platelet disorders in humans, biomedical aspects: Biology, Pathobiology and bioclinical

Las enfermedades genéticas plaquetarias son desórdenes heterogéneos, algunos de ellos muy raros, quese presentan en la medicina clínica, caracterizados por trobocitopenia, plaquetas grandes (macrotrombocitopenias)y signos variables de hemorragia, así como trombosis en otros casos. La patogénesis ypatofisiología es bastante desconocida y el propósito de este artículo es proveer una estructura lógicaque resuma el conocimiento actual.

Clinical Characteristics of Autosomal Dominant Giant Platelet Syndromes and Mutation Analysis of MYH9 / 대한혈액학회지

BACKGROUND: The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Dohle-like leukocyte inclusions are caused by MYH9 mutation, a gene encoding the nonmuscle myosin heavy chain-IIA. This study was aimed to identify the Korean GPS patients and to define clinical findings and molecular characteristics on them. METHODS: After taking a family history, platelets were counted using hematologic autoanalyzer and peripheral blood smear (PBS) was examined for platelet size and number, and the presence of leukocyte inclusions. Mutation of MYH9 was studied from mononuclear cells from PB by direct sequencing of previously known 8 exons after PCR amplification of genomic DNA. RESULTS: Twenty patients from 5 unrelated families were diagnosed as GPS. Giant platelets, greater than red cells on PBS, were found to be 3.1% of platelet (range, 1~11%). The median platelet count was 61,000/microliter. Inclusion bodies were found in 3 families. Two families had previously reported mutations. Family I had Arg1944Ter in exon 40, located in the tail portion of myosin, while Family IV had Lys373Asn in exon 10, located in the proximal portion of myosin head. The mutations were found only in affected patients, but not in normal siblings or unrelated families. CONCLUSION: In this study, we identified several families with autosomal dominant GPS. Two families had known MYH9 mutations, Arg1944Ter and Lys373Asn. The search for unknown mutations in the remaining families as well as study of protein structural and functional alteration seems to be necessary for further delineation of these rare genetic disorders.

Giant platelet syndrome / 소아과

Giant platelet syndrome is a group of unique disorders characterized by the presence of abnormally large platelets, and usually accompanied by thrombocytopenia. Most cases of giant platelets are encountered in idiopathic thrombocytopenic purpura(ITP). In contrast, inherited giant platelet disorders, a group of heterogeneous diseases, are rare. Bernard-Soulier syndrome and its variants, and MYH9 related diseases have been defined at the molecular level. Abnormalities in transcription factors are implicated in a couple of macrothrombocytopenia syndromes. However, the molecular defects are unknown in gray platelet syndrome. It is important to make a proper diagnosis of congenital macrothrombocytopenia to avoid unnecessary medications and potentially dangerous treatment for presumed ITP.

Síndrome de Bernanrd-Soulier / Bernard Soulier Syndrom

A síndrome de Bernard-Soulier (SBS) trata-se de uma rara enfermidade que se caracteriza por tempo de sangramentoprolongado, presença de trombocitopenia e plaquetas gigantes. Clinicamente, os portadores sofrem de distúrbios hemorrágicos que vão de discretos a severos, como: epistaxes, menorragia, melena, sangramento gengival, entre outros. Trata-se de uma doença detransmissão hereditária autossômica recessiva, com maior prevalência em filhos de pais consangüíneos. A nível molecular, sua causa predominante deve-se a diversas mutações, como a deleção de dinucleotídeos, alterando a leitura estrutural da região que decodifica a glicoproteína (GP), produzindo, assim, proteínas alteradas que normalmente teriam um papel especial na conformação e estabilidade da expressão do complexo GP IbIX-V, que é responsável pela eficácia funcional das plaquetas. Esta revisão de literatura tem como objetivo mostrar a importância do conhecimento dessa alteração plaquetária, esclarecer dúvidas sobre a SBS e apontar que a presença de plaquetas bizarras no esfregaço sangüíneo é o mais importante indício desta síndrome, o que diferencia a SBS de outros distúrbios de hemostasia, como a Púrpura Trombocitopênica Imunológica e a Doença de Von Willebrand, na rotina laboratorial.

Calves born under tropical conditions after direct transfer of cryopreserved in vitro produced embryos

En el presente estudio se comparó el desempeño de 56 novillas doble propósito que resultaron preñadas luego de la transferencia directa de embriones producidos in vitro cultivados en un medio suplementado con suero o en uno químicamente definido. No se observaron diferencias en las tasas de aborto (30,43% vs 24,24%), distocias (52,17% vs 51,52%) y parto normal (17,39% vs 24,24%) entre las novillas que recibieron embriones cultivados en el medio suplemento con suero y las que recibieron embriones cultivados en el medio químicamente definido. El sexo de la cría afectó significativamente el porcentaje de distocias, 83,33% para machos y 50% para hembras, (P<0,05). El peso al nacimiento de los becerros tampoco se vio afectado (p>0,05) por la suplementación sérica durante el cultivo (46,86 ± 2,04 kg, para los becerros derivados de los embriones cultivados en el medio suplementado con suero y 46,28 ± 1,42 kg, para los derivados de los embriones cultivados en el medio químicamente definido) ni por el sexo de la cría (machos 47,20 ± 1,50 kg y hembras, 45,45 ± 1,84 kg). El peso de los becerros que nacieron muertos o que murieron luego del nacimiento fue significativamente (P< 0,05) mayor (51,92 ± 1,76 kg) al de los becerros que sobrevivieron (43,88 ± 1,22 kg). La sobrevivencia perinatal no se vió afectada ni la suplementación sérica durante el cultivo embrionario, ni por el sexo de los becerros o el nacimiento de un parto distócico. En conclusión, la presencia de suero en el medio de cultivo no afectó el desempeño de las novillas doble propósito que resultaron preñadas luego de la transferencia de embriones producidos in vitro. En este estudio se observó la presencia de becerros con síndrome del recién nacido gigante evidenciado por un alto peso al nacimiento y una alta tasa de abortos y distocias.

survey on platelet surface glycoprotiens in patients with bernard-souliar syndrome by flowcytometry

The gold standard diagnosis of the Bernard-Souliar syndrome [BSS], a rare disease, is to prove the absence of Ib/IX surface complex on platelets with the use of aggregometric methods. Flowcytometry is an ideal method in analysis of surface markers on cells. The use of flowcytometric analysis in diagnosis of Bernard-Souliar syndrome. 15 suspected BSS, 20 healthy persons as control group and 3 ITP patints were selected to be analysed for the presence of GPIb alpha and GPIIIa on the surface of platelets with the application of FITC conjugated monoclonal antibodies using flowcytometry. All healthy persons in control group and 3 ITP patients showed normal expression of both glycoprotiens on platelets using flowcytometry. All 15 suspected BSS patients showed lack of GPIb? but a normal expression of GPIIIa on platelets. The application of flowcytometry for diagnosis of BSS is a quick, accurate, and precise method, which together with aggregometric method can be used for diagnosis of BSS

Molecular biological study of glycoprotein IX gene defect in Bernard-Soulier syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify a mutation G2113-->A in the glycoprotein (GP)IX gene associated with Bernard-Soulier syndrome (BSS) and to investigate BSS pathogenesis.</p><p><b>METHODS</b>Allele-specific restriction enzyme was used to analyze the samples of patient, her mother, her brother and 40 healthy volunteers. Site-directed mutagenesis was performed to construct a expression vector PD-IXG2113A harboring the mutation G2113-->A. Chinese hamster ovary (CHO) cells were transiently cotransfected with plasmids harboring the entire coding region of GPIbalpha, GPIbeta and GPIX or mutant GPIX, respectively. Expression of GPIbalpha and GPIX in transfected CHO cells were analysed with flow cytometer. GPIbalpha and GPIX in the cytoplasma of transfected CHO cells were analysed by immunostaining and Western blotting.</p><p><b>RESULTS</b>The patient was found to be homozygosity of the substitution, her mother and her brother be heterozygous. Expressions of GPIbalpha and GPIX in mutant CHO cells were remarkably reduced, but abundant in the cytoplasma.</p><p><b>CONCLUSION</b>The mutation of Ala139(GCC)-->Thr(ACC) in the GPIX did not affect synthesis and assembly of GPIb/IX complex but influence its anchoring and expression on the cell surface, which was responsible for BSS.</p>

MYH9-related Disorder in a Family: Autosomal Dominant Epstein Giant Platelet Syndrome / 대한소아혈액종양학회지

The term MYH9-related disorders indicates a group of autosomal dominant illnesses, formerly known as May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome and Epstein syndrome, caused by mutations of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). We experienced a family with macrothrombocytopenia without leukocyte inclusion. A 5-year-old girl was found to have macrothrombocytopenia incidentally. Her father also had macrothromtocytopenia, but had been suffering from hearing loss and chronic renal failure. Meticulous search by light and electron microscopy failed to detect leukocyte inclusions. To our knowledge, these cases seem to be the first description of autosomal dominant Epstein giant platelet syndrome in Korea.

Report of a patient with spontaneous aggregation of his giant and morphologically abnormal platelets / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the pathological and clinical characteristics of a patient with spontaneous platelet aggregation of his giant and morphologically abnormal platelets.</p><p><b>METHODS</b>Platelet size and structure were observed under light microscope and electron microscope. Platelet aggregation was measured turbidometrically. Platelet glycoproteins (GP) were analyzed using flow cytometry. PCR and DNA sequencing were performed to identify the gene abnormality.</p><p><b>RESULTS</b>The patient had spontaneous platelet aggregation of giant platelets with thickened plasma membrane and increased number of granules in various shapes. Aspirin and ticlopidine did not affect the spontaneous aggregation. The expression of GP I b, GP II b, GP III a and P-selectin in the platelet membrane were in normal range. Results of gene analyses for GP I balpha, GP I bbeta and GPIX were also normal.</p><p><b>CONCLUSION</b>Both morphological and functional abnormalities of the platelets from the patient were clearly distinguishable from that of other hereditary giant platelet disorders. It would probably represent a novel platelet disorder which had not been reported to date.</p>

Trombocitopatías: casos clínicos / Bleeding diseases: clinical cases

Se presentan dos casos de baja prevalencia pero que en algunas ocasiones adquieren gran complejidad en su tratamiento, dado que necesitan el empleo de transfusión de plaquetas sanguíneas como terapia sistémica, un procedimiento que comprende grandes inconvenientes. Las plaquetas deben ser transfundidas dentro de un período no superior a 6 horas, dado que poseen una gran labilidad y pierden el 80 por ciento de su actividad. Estas son afecciones genéticas y hemorrágicas debidas a la ausencia de glucoproteínas de la membrana plaquetaria

Utilidad de la desmopresina en cuatro casos de trombocitopatías asociadas a plaquetas gigantes / Utility of desmopressin in four cases of thrombocytopathy with giant platelets

La agresión plaquetaria requiere de complejos glucoproteicos plaquetarios (Gp), del factor de von Willebrand y del ADP. Los síndromes de Bernard-Soulier (BS) y de la plaqueta gris (SPG) son defectos hereditarios de la función plaquetaria caracterizados por ausencia del Gp lb-lX y ausencia de gránulos alfa, respectivamente, con presencia en ambos síndromes de hemorragias mucocutáneas, tiempo de sangrado (TS) prolongado, trombocitopenia moderada y plaquetas gigantes. Existen informes que la desmopresina (DDAVP) acorta el TS en algunos pacientes con defectos de la función plaquetaria. El objetivo de este estudio fue evaluar la respuesta a DDVAP en cuatro mujeres (2 con SPG + enfermedad de marfán y 2 con BS). Todas presentaron hemorragias mucocutáneas de intensidad variable con TS> 10 minutos, cuenta de plaquetas (CP) entre 40 y 88 X 10/L y defectos en la agregación plaquetaria. El DDAVP se administró a dosis de 0.3µg X kg/dosis única en solución salina, por vía intravenosa durante 30 a 45 minutos. Todas las pacientes fueron estudiadas antes y después de la administración del DDAVP (TS, CP, factor 4 plaquetarios volumen plaquetario medio, factores F.VIII:C, FvW:Ag, FvW:RiCof y agregación plaquetarías). El TS se corrigió a < 6 minutos y se incrementaron los niveles de F.VIII:C, FvW:Ag y FvW:RiCof (> 100 UI/dL); las manifestaciones hemorrágicas desaparecieron. Concluímos que hubo una buena respuesta al DDAVP, la cual puede estar relacionada con mejoría de la adhesión plaquetaria e incremento de multínumeros del factor de von Willibrand

Epistaxe como manifestaçäo da síndrome de Bernard-Soulier / Epistaxis as a manifestation of Bernard-Soulier Syndrome

Objetivo: Chamar a atençäo dos pediatras para uma causa rara de epistaxes severas de repetiçäo. Métodos: Os autoes descrevem um caso de criança com Síndrome de Bernard-Soulieur e fazem uma revisäo de relatos da Síndrome em língua inglesa existentes no MEDLINE desde 1970. Resultados: É descrito um menino de 3 anos e 3 meses, com quadro de epistaxes volumosas de repetiçäo, com importante repercussäo emodinâmica, no qual foram necessárias várias transfusöes de sangue e hemoderivados. Foram estabelecidas diversas suspeitas diagnósticas até que, pelo exame de sangue periférico, identificaram-se macroplaquetas. o diagnóstico final foi de Síndrome de Bernard-Soulieur, e procedeu-se à embolizaçäo da artéria maxilar para solucionar as epistaxes de repetiçä ...

Estudio de la actividad procoagulante de las plaquetas en el síndrome de Bernard Soulier / Procoagulant activity of platelets study in the Bernard Soulier's syndrome

En el síndrome de Bernard soulier (SBS) han sido demostradas alteraciones específicas que dan lugar a un trastorno en la adhesividad plaquetaria. También se le han atribuido otros defectos que condicionan una alteración en el actividad procoagulante de sus mismas plaquetas, los cuales no han logrado definirse satisfactoriamente. En el presente trabajo se estduió el efecto procoagulante de las plaquetas, en cuatro pacientes con SBS, comparándolo con los resultados en controles sanos y enfermos trombocitopénica, para tal fin se efectuaron modificaciones en el cosumo de protrombina (CP) y tiempo de recalcificación del plasma, para evaluar el efecto de la trombocitopenia y el de plasmas con deficiencias intensas y específicas de factores de coagulación V, VIII y XI sobre el mecanismo procoagulante de las plaquetas con SBS. Los resultados observados difieren de los informados por otros investigadores, pues no se detectó ningún defecto en la actividad procoagulante en las plaquetas de los pacientes con SBS, considerando que su actividad procoagulante es normal, o bien, que existan variante de dicho síndrome

Síndrome de Bernard-Soulier na gestaçäo. Relato de caso / Bernard-Soulier syndrome and pregnancy. A case report

É relatada a evoluçäo de gestaçäo, parto e puerpério de uma paciente portadora de síndrome de Bernard-Soulier. A evoluçäo pré-natal foi favorável, tendo sido necessárias três transfusöes de plaquetas. O parto foi por cesariana eletiva no termo, tendo em vista um suposto maior risco de sangramento incontrolável no parto vaginal. O pós-operatório desenvolveu-se sem intercorrências

Bernard-Soulier syndrome: a case report.

An adopted Thai girl has been followed at Children's Hospital, Bangkok, since she was 8 months old. The diagnosis of Bernard-Soulier syndrome was made, based on the clinical features of easy bruising, purpura, petechial hemorrhages and recurrent epistaxis. The abnormal laboratory tests included giant platelets with dark stained granules, mild to moderate thrombocytopenia, prolonged bleeding time, absence of ristocetin induced agglutination but normal ristocetin cofactor, factor VIII coagulant activity and von Willebrand factor antigen. These findings suggested the absence of glycoprotein Ib (GPIb) on the platelet membrane. The genetic transmission can not be evaluated in this patient.