A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

IgG4-related disease associated with immune thrombocytopenia: A clinical case report

Autoimmune pancreatitis is a characteristic manifestation of the spectrum of the disease related to IgG4, a rare autoimmune disorder that presents clinically with obstructive jaundice due to the infiltration of plasma cells and fibrosis in the pancreas. There may be other symptoms in case of involvement of other organs, and in very rare cases there is hematological involvement. We present the case of an adult man with signs of cholestasis secondary to type I autoimmune pancreatitis, with involvement of other organs and associated with thrombocytopenia that improved with systemic corticosteroid-based immunosuppressive treatment, after which the patient showed favorable clinical and analytical evolution over time.

La pancreatitis autoimmune es una manifestación característica del espectro de la enfermedad relacionada con IgG4, trastorno raro de tipo autoinmune que se presenta clínicamente con ictericia obstructiva debido a la infiltración de células plasmáticas y fibrosis en el páncreas; puede presentarse con otra sintomatología en caso de afectación de otros órganos y en muy raras ocasiones hay compromiso hematológico. Se presenta el caso de un hombre adulto con signos de colestasis secundaria a una pancreatitis autoinmune tipo i, con compromiso de otros órganos y asociada con trombocitopenia que mejoró con el tratamiento inmunosupresor a base de corticoide sistémico, luego del cual se observó una evolución favorable en cuanto a la clínica y analítica en el transcurso del tiempo.

Splanchnic vein thrombosis as a manifestation of latent myeloproliferative neoplasm associated with sticky platelet syndrome / Trombosis esplácnica como presentación de neoplasia mieloproliferativa latente asociada con síndrome de plaqueta pegajosa

Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.

Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.

Molecular polymorphism Analysis on CD36 Deficiency among Platelet Blood Donors in Shenzhen / 中国实验血液学杂志

OBJECTIVE@#To analyze the molecular polymorphisms of CD36 among 58 blood donors with CD36 deficiency and compare with CD36 positive controls.@*METHODS@#A total of 58 donors with CD36 deficiency during a screening conducted in the laboratory from September 2019 to December 2020 were enrolled as the test group, including 39 males and 19 females, while 120 platelet donors with CD36 positive were randomly selected as the controls, including 76 males and 44 females. All of the subjects were Han nationality. The PCR-SBT method was used to detect coding region of CD36 gene, and molecular mutations were compared with those CD36 positive controls.@*RESULTS@#Among the 58 donors with CD36 deficiency, mutations appears in 32 individuals. The detection rate for type I was 71.43% (5/7), and type II was 51.92% (27/52), while among the 120 controls, mutations appears in 12 donors (10%). In the CD36 antigen-deficient donors, 16 variations were found, in which 329-330 del AC with the highest frequency accounted for 20.69%, followed by 1228-1239 del ATTGTGCCTATT(15.52%) and 1156 C>T(10.34%). Two variations, 198-205 del GATCTTTG and 220 C>T, led to premature termination of translation; four mutations, 329-330 del AC, 560 ins T, 1011-1049 39bp dupl and 1343-1344 ins TCTT, caused translation frame shift; 1228-1239 del ATTGTGCCTATT led to deletion of four amino acids (Ile-Val-Pro-Ile) at sites 410-413 of the peptide chain. The 1140 T>A and 1275 G>A were synonymous mutations, and the other 7 mutations resulted in the substitution of single nucleotide. The platelet expression in the donors of CD36 positive with 329-330 del AC or 1228-1239 del ATTGTGCCTATT mutation (heterozygote) was lower than those CD36 positive individuals without mutations (homozygote).@*CONCLUSION@#Multiple gene mutations in the CD36 coding region may cause CD36 deficiency, and the heterozygous individuals with mutations may lead to CD36 antigen reduction or deletion. Mutation is not detected in 44.83% of CD36 deficient individuals, there may be some other reasons for the CD36 antigen deficiency.

Trastornos plaquetarios hereditarios poco frecuentes: patología molecular y aspectos diagnósticos / Infrequent hereditary platelets disorders: molecular pathology and diagnostic aspects

Introducción: Las plaquetas tienen una función clave en la hemostasia primaria a través de cuatro mecanismos fundamentales: adhesión, agregación, secreción y actividad procoagulante, todos controlados genéticamente por más de 50 genes asociados que han sido identificados. Las manifestaciones clínicas en las alteraciones hereditarias de las plaquetas suelen ser variables; aunque estas alteraciones de la coagulación suelen presentarse con una trombocitopenia notoria, también pueden exhibir trombocitopatías, en las cuales la capacidad hemostática de las plaquetas resulta afectada sin variar su número. Por tanto, existen gran variedad de manifestaciones fenotípicas y mutaciones en relación con la función plaquetaria, algunas de las cuales se explicarán más adelante. Objetivo: Realizar revisión práctica sobre mutaciones plaquetarias hereditarias de baja incidencia y destacar la importancia de su conocimiento, correcto diagnóstico, y tratamiento precoz. Métodos: Se realizó revisión literaria en inglés y españolen MEDLINE, EMBASE, Lilacs y ScienceDirect desde mayo 2019 hasta abril 2020, con el uso de combinación de palabras clave y términos MeSH relacionados con trombastenia, genética médica, hemostasis, agregación plaquetaria, trombopoyesis. Se efectuó análisis y resumen de la bibliografía revisada. Conclusión: Entre las alteraciones hereditarias de las plaquetas se pueden encontrar defectos en todos los mecanismos en que participan; sin embargo, la confirmación diagnóstica sigue siendo complicada por el tiempo y el costo que representa lo que ocasiona diagnósticos inadecuados que impactan en el manejo clínico y la evolución(AU)

Introduction: Platelets have a key role in primary hemostasis through four main mechanisms: adhesion, aggregation, secretion and procoagulant activity, all of these controlled by over 50 associated genes that have been identified. Clinical signs of hereditary platelets alterations are usually variable; even though these disorders of hemostasis generally course with a notorious thrombocytopenia, they also might have thrombocytopathies, in which the hemostatic capacity of platelets is affected without altering its number. According to this, there's a great variety of phenotypic manifestations and mutations that affect platelet function, some of these will be explained later on. Objective: To make a practical review of hereditary platelets mutations that have low incidence in population and to highlight the importance of knowing about them, how to diagnose them and early treatment. Methods: A review of literature in both Spanish and English, was done based on MEDLINE, EMBASE, Lilacs and ScienceDirect, during May 2019 and April 2020 using key words and MeSH terms such as thrombasthenia, medical genetics, hemostasis, platelets aggregation, thromopoiesis. Then, an analysis and summary of the reviewed bibliography was carried out. Conclusion: Among the hereditary alterations of platelets, many defects can be found in every mechanism involved; however, diagnostic confirmation is still complicated due to time and cost, causing inaccurate diagnoses that impact on clinic management and evolution(AU)

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.

Pruebas de función plaquetaria por el sistema PFA-200 / PFA-200 system for platelet dysfunction analysis

Las pruebas de función plaquetaria realizadas con el analizador PFA-200 (del inglés, Platelet Function Analyzer) han venido reemplazando el tiempo de sangría, una prueba ya obsoleta, de acuerdo con el College of American Pathologists (CAP) y la American Society for Clinical Pathology (ASCP). Este analizador, mediante un sistema que utiliza cartuchos, posee la capacidad de simular in vitro las condiciones hemodinámicas del paciente para el tamizaje rápido, sencillo y automatizado de la disfunción plaquetaria. Las pruebas son de utilidad para evaluar la función plaquetaria en pacientes con alteraciones como enfermedad de von Willebrand y otras trombocitopatías congénitas o adquiridas, y evalúa la disfunción plaquetaria causada por inhibidores de la agregación plaquetaria, como la aspirina. Además, son de gran utilidad para el tamizaje prequirúrgico y en los embarazos de alto riego. Este sistema ofrece con su más reciente prueba, la INNOVANCE® PFA-200 P2Y, la posibilidad de evaluar la respuesta de pacientes que están siendo tratados con antagonistas del receptor plaquetario P2Y12, como son clopidogrel, prasugrel y ticagrelor, determinando el porcentaje de adhesión y agregación plaquetaria, logrando discriminar entre un paciente antiagregado y un paciente resistente al tratamiento

Two Novel Mutations at the CD36 Gene Splicing Sites and Their Molecular Basis for the CD36 Deficiency / 中国实验血液学杂志

OBJECTIVE@#To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them.@*METHODS@#DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population.@*RESULTS@#Novel mutation of c.430 -1G>C was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2T>G at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1G>C could lead to the production of the two CD36 mRNA transcript variants: c.429_430ins［430-17_430-2;C］(p.Ala144fsTer1) and c.430_609del(p.Ala144_Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2T>G could lead to the production of CD36 mRNA transcript variant of c.819_1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1G>C was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2T>G was 2.73% (3/110) and 0 (0/296), respectively.@*CONCLUSION@#This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.

Ancho de distribución plaquetaria como predictor de preeclampsia severa / Platelet distribution width as a marker for the development of severe preeclampsia

Resumen Introducción: La fisiopatología de la preeclampsia no está dilucidada por completo, diferentes índices plaquetarios dentro de los que se incluye el ancho de distribución plaquetaria (ADP) podrían ser utilizado para predecir la severidad en esta condición. Objetivo: Analizar el comportamiento del ADP en el desarrollo de severidad en preeclampsia en mujeres atendidas en la unidad de medicina materno-fetal del Hospital Simón Bolívar de Bogotá, Colombia. Materiales y métodos: Estudio de corte trasversal analítico en 105 pacientes con trastorno hipertensivo asociado al embarazo, preeclampsia y preeclampsia severa. Se analizó el comportamiento del ADP en una población de mujeres hipertensas con preeclampsia mediante una curva de análisis ''Receiver Operating Characteristic'' (ROC) para estimar la sensibilidad, tasa de falsos positivos, razón de probabilidad positiva y negativa de la prueba como marcador de desarrollo de severidad Resultados: El ADP tuvo un ascenso significativo mayor en pacientes donde su progresión de enfermedad desarrollaron características de severidad. En la curva ROC el área bajo la curva para del ADP como predictor de severidad en la preeclampsia fué de 0.68 Conclusión: El ADP es un índice plaquetario que aumentó significativamente en las mujeres con preeclampsia con características de severidad. El ADP podría ser un marcador para la predicción de severidad de la preeclampsia.

Abstract Introduction: The pathophysiology of preeclampsia is not completely elucidated. Different platelet indices, including the platelet distribution width (PDW), could be used to predict the severity of this condition. Objective: To analyze the behavior of PDW in the severity development of preeclampsia in women treated in the maternal-fetal medicine unit of Hospital Simón Bolívar in Bogotá, Colombia. Materials and methods: This is an analytical cross-sectional study in 105 patients with hypertensive disorder associated with pregnancy, preeclampsia and severe preeclampsia. We analyzed the behavior of PDW in a population of hypertensive women with preeclampsia using a curve of analysis '' Receiver Operating Characteristic '' (ROC) to estimate the sensitivity, false positive rate, positive and negative likelihood ratio of the test as a marker of development of severity Results: PDW had a higher significant increase in patients where their disease progression developed severity characteristics. In the ROC curve, the area under the curve for PDW as a predictor of severity in preeclampsia was 0.68. Conclusion: PDW is a platelet index that increased significantly in women with preeclampsia with severity characteristics. PDW could be a marker for the prediction of severity of preeclampsia.

High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases / Alta Atividade Plaquetária Residual em Resposta ao Ácido Acetilsalicílico na Síndrome Coronariana Aguda Sem Supra de ST: Comparação entre as Fases Aguda e Tardia

Abstract Background: High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. Objective: The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Methods: Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. Results: According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. Conclusion: The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.

Resumo Fundamento: A alta atividade plaquetária (AAP) durante a terapia com ácido acetilsalicílico (AAS) é fator de mau prognóstico nas síndromes coronarianas agudas (SCA). A prevalência de AAP durante a SCA é maior do que a relatada na doença estável. No entanto, não está claro se esta prevalência de AAP é um fenômeno transitório ou característica dessa população de alto risco. Objetivo: O objetivo principal é comparar, em uma mesma população, os efeitos do AAS sobre a função plaquetária nas fases inicial e tardia da SCA. Os objetivos secundários são: correlação entre os testes entre si e a relação entre os testes e a variação dos marcadores inflamatórios (proteína C reativa e interleucina-6). Métodos: Foram estudados prospectivamente 70 pacientes com SCA sem elevação de ST (SCSST) em uso de 100 a 200 mg de AAS por dia por pelo menos 7 dias. A função plaquetária foi avaliada nas primeiras 48 horas e 3 meses após por quatro métodos: VerifyNow™ (VFN), agregometria de sangue total (AST) com ácido araquidônico (AA) e colágeno como agonistas, e analisador de função plaquetária (PFA). O nível de significância estatístico considerado foi < 0,05. Resultados: A média de idade foi de 65 ±9,7 anos e 54% da população eram do sexo feminino. De acordo com os métodos mais específicos (AST com AA e VFN), a incidência de AAP foi significativamente maior na fase inicial, em relação à tardia: AST com AA 31% versus 13%, p = 0,015; VFN 32% versus 16%, p = 0,049. Os outros métodos testados, menos específicos para o AAS, não mostraram diferenças significativas entre as fases. A correlação entre os métodos foi fraca ou moderada (r variando de 0,3 a 0,5, p < 0,05), e não houve associações significativas entre AAP e marcadores inflamatórios. Conclusão: A prevalência de AAP durante a terapia com AAS, avaliada por métodos específicos para cicloxigenase 1 (COX-1), é maior durante a fase aguda do que na tardia da SCASST.

Anti-CD36 Mediated Platelet Transfusion Refractoriness and Related Cases After Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the cases of platelet transfusion refractoriness after received HLA-matched unrelated donor hematopoietic stem cell transplantation, to analyze and identify the phenotype and genotype of CD36 in both the patient and stem cell donor, as well as the characteristic of antibody induced platelet transfusion refractoriness, and to analyse the efficacy of matched CD36-deficiency platelets transfusions.</p><p><b>METHODS</b>The CD36 expression on platelet and monocyte was analyzed by flow cytometry (FCM) in both patient and donor. Polymerase chain reaction sequence-based typing (PCR-SBT) was used to analyze the exons sequence of CD36 and HPA. Fast monoclonal antibody-specific immobilization of platelet antigen (F-MAIPA) and FCM were used to identify platelet antibodies in the patient. Short tandem repeat polymerase chain reaction (STR-PCR) was applied to monitor engraftment evidence. The platelet level was monitored. CD36- deficiency donor's platelets were selected from CD36- deficiency donor blood bank.</p><p><b>RESULTS</b>The donor was CD36 positive and the patient was typed I CD36 deficiency. The anti-CD36 antibody was identified in patient's serum (after transplantation), while the HLA and HPA-related antibodies were excluded. Sequence analysis of CD36 exon in the patient showed Exon 6 -1G>C(Change in splicing site) homozygote, which was a novel CD36 mutation. STR, HPA and CD36 of the patient (complete chimerism) were conversed to that of donor gene types on day 18 after allo-HSCT. The positive CD36 expression on platelet and monocyte in the patient was observed on day 96 after allo-HSCT. The patient showed the platelet transfusion refractoriness which was significantly improved after platelets transfusions from CD36 deficiency donors.</p><p><b>CONCLUSION</b>Stem cell transplants resulted in anti-CD36 and caused platelet transfusion refractoriness, that was first reported in China. To ensure the efficacy of platelet transfusion, the CD36-deficiency patient should receive CD36 deficiency platelets for transfusion.</p>

Evans syndrome complicated by chronic hypertension with superimposed pre-eclampsia with HELLP syndrome in pregnancy: A case report / Philippine Journal of Obstetrics and Gynecology

The case of a pregnant woman initially presenting with low platelets and low haemoglobin and subsequently diagnosed as a case of Evans Syndrome is presented. Owing to its extremely low incidence, little research exists investigating pregnancies complicated by Evans Syndrome. Although diagnosis is simple and straightforward, management of a pregnancy of this nature has proven to be complex and challenging. Further complicating the case and its management is the concurrent diagnosis of Chronic Hypertension with Superimposed Pre-eclampsia, in complete HELLP Syndrome. Pre-eclampsia in the background of Evans Syndrome makes this case a truly interesting case. The individual effects of the two disease entities in a single patient are discussed in this report.

Evans syndrome complicated by chronic hypertension with superimposed pre-eclampsia with HELLP syndrome in pregnancy: A case report / Philippine Journal of Obstetrics and Gynecology

The case of a pregnant woman initially presenting with low platelets and low haemoglobin and subsequently diagnosed as a case of Evans Syndrome is presented. Owing to its extremely low incidence, little research exists investigating pregnancies complicated by Evans Syndrome. Although diagnosis is simple and straightforward, management of a pregnancy of this nature has proven to be complex and challenging. Further complicating the case and its management is the concurrent diagnosis of Chronic Hypertension with Superimposed Pre-eclampsia, in complete HELLP Syndrome. Pre-eclampsia in the background of Evans Syndrome makes this case a truly interesting case. The individual effects of the two disease entities in a single patient are discussed in this report.

Reacciones adversas a fármacos antituberculosos en pediatría: A propósito de 4 hermanos / Adverse Reactions to Antituberculosis Drugs in Pediatrics. Apropos of 4 Brothers

Se denomina efecto adverso a fármacos antituberculosos (RAFAs), a una respuesta nociva y no deseada de uno o varios de los fármacos utilizados, para profilaxis, diagnostico o tratamiento de la enfermedad tuberculosa. Para adjudicarlos a la medicación se debe tener en cuenta que las dosis sean adecuadas, descartar interacciones medicamentosas y comorbilidades. Es necesario conocerlos y monitorizarlos, para evitar posibles riesgos de morbi-mortalidad. Objetivo: comunicar el caso de 4 hermanos que presentaron RAFAs, a más de 1 fármaco antituberculoso.

It is called tuberculous adverse drug effect (RAFAs), to a noxious response and not desired to one or more of the drugs used for prophylaxis, diagnosis or treatment of tuberculous disease. To attribute them to the medication, it is necessary to take into account that doses should be normal; also dismiss drug interactions and co-morbidities. It is necessary to know them and monitor them, to avoid possible risks of morbidity and mortality. Objective: to communicate the case of four brothers who presented RAFAs, to more than one TB drug.

A novel CD36 mutation T538C (Trp180Arg) results in CD36 deficiency and establishment of a genotyping method for the novel mutation based on sequence-specific primer PCR / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular basis for a CD36 deficiency individual and distribution of CD36 gene mutation in Guangxi population.</p><p><b>METHODS</b>A female individual was studied. CD36 phenotype was detected by monoclonal antibody immobilization of platelet antigens assay (MAIPA) and flow cytometry (FCM). The coding regions of the CD36 gene were sequenced. A DNA-based polymerase chain reaction-sequence specific primer (PCR-SSP) assay was used to verify the identified mutation. Cell lines expressing the mutant and wild-type CD36[CD36(MT) and CD36(WT)] were established, with the expression of CD36 determined by Western blotting. The distribution of CD36 gene mutation was investigated among 1010 unrelated individuals with the PCR-SSP assay.</p><p><b>RESULTS</b>Both MAIPA and FCM assays showed that the patient had type II CD36 deficiency. DNA sequencing showed that she has carried a heterozygous mutation T538C (Trp180Arg) in the exon 6 of CD36. Sequencing of cDNA clone confirmed that there was a nucleotide substitution at position 538 (538T>C). Western blotting also confirmed that the CD36 did not express on the CD36(MT) cell line that expressed the 538C mutant, but did express on the CD36(WT) cell line. The novel CD36 mutation T538C was further verified with 100% concordance of genotyping results by DNA-based PCR-SSP assay and 1010 unrelated individuals. No CD36 538C allele was detected among the 1010 individuals.</p><p><b>CONCLUSION</b>This study has identified a novel CD36 mutation T538C(Trp180Arg)(GenBank: HM217022.1), and established a genotyping method for the novel sequence-specific primer PCR. The novel mutation is rare in Guangxi and can cause type II CD36 deficiency.</p>

CD36 Antigen Deficiency and Platelet Transfusion / 中国实验血液学杂志

CD36 is a transmembrane glycoprotein, a multi-ligand receptor, possesses various biological functions. CD36 deficiency may stimulate the body to produce anti-CD36 alloimmune antibodies through the several pathways, such as blood transfusion, pregnancy or organ transplantation and so on, leading to the refractoriness of immune platelet transfusion and other diseases. The recent research advances of CD36 deficiency and its molecular biological basis, platelet transfusion and CD36 antibody detection are summarized briefey in this review.

Inhibidor lúpico en situaciones clínicas diferentes al síndrome antifosfolipídico / Lupus inhibitor in clinical situations other than antiphospholipid syndrome

El inhibidor lúpico (IL) es uno de los criterios de laboratorio para Síndrome Antifosfolipídico (SAF); sin embargo, puede detectarse en individuos asintomáticos o estar asociado a otras situaciones clínicas. Presentamos un análisis retrospectivo de 1000 exámenes consecutivos para IL (TTPA, DRVVT) de los cuales 249 casos no presentaban criterios clínicos de SAF. Aplicando los criterios SSC-ISTH, hallamos IL+ en 27,30% (205/751) y 43,37% (108/249) de los casos con y sin criterios clínicos de SAF respectivamente; analizándose en estos últimos casos las características clínicas y de laboratorio. Contexto clínico de casos IL+ sin SAF: 18,52% asintomáticos, 34,26% síntomas de sangrado y 47,22% otras manifestaciones. Otras alteraciones de laboratorio en casos IL+ sin SAF, con síntomas de sangrado: detectamos alteraciones plaquetarias, descenso de VWF:RCo y/o VWF:Ag, disminución de FVIII, FV, FVII, FXI o fibrinógeno e hiperfibrinolisis en el 54,05% de los casos. El análisis mostró detección de IL+ en un número importante de estudios (108/1000) sin criterios SAF. Los casos con IL+ y sangrado representan un desafío particular, al requerir evaluar otros posibles defectos subyacentes, que pudiesen justificar el comportamiento clínico. La detección e identificación de defectos combinados requiriere de un análisis minucioso, a fin de alcanzar un diagnóstico correcto, esencial para tomar decisiones terapéuticas adecuadas. (AU)

Despite lupus anticoagulant (LA) is one of the laboratory criteria for antiphospholipid syndrome (APS), it can be present in asymptomatic subjects or it can be associated with other clinical settings. We present a retrospective analysis of 1000 consecutive LA assays (APTT, DRVVT), 249 of them were performed in patients without clinical criteria for APS. According to ISTH criteria, positive LA was found in 27.30% (205/751) and 43.37% (108/249) of cases with or without APS criteria respectively; in the last group, the analysis of clinical background and laboratory characteristics was done. Clinical background of LA+ cases without APS: 18.52% asymptomatic, 34.26% bleeding symptoms and 47.22% other clinical settings. Other abnormal laboratory tests in LA+ cases without APS and bleeding symptoms: platelet dysfunction; low VWF:RCo and/or VWF:Ag; decrease of FVIII, FV, FVII, FXI or fibrinogen and hyperfibrinolysis were found in the 54.05% of the cases. The analysis showed positive LA in an important number of cases (108/1000) without criteria of APS. Those LA+ cases with bleeding symptoms represent a particular challenge because other possible underlying defects have to be analysed in order to explain the clinical behaviour. The detection and identifications of combined defects required a careful analysis in order to achieve accurate diagnosis, essential for therapeutic decisions. (AU)

The role of point-of-care assessment of platelet function in predicting postoperative bleeding and transfusion requirements after coronary artery bypass grafting.

Objective: Objective platelet function assessment after cardiac surgery can predict postoperative blood loss, guide transfusion requirements and discriminate the need for surgical re‑exploration. We conducted this study to assess the predictive value of point‑of‑care testing platelet function using the Multiplate® device. Methods: Patients undergoing isolated coronary artery bypass grafting were prospectively recruited (n = 84). Group A (n = 42) patients were on anti‑platelet therapy until surgery; patients in Group B (n = 42) stopped anti‑platelet treatment at least 5 days preoperatively. Multiplate® and thromboelastography (TEG) tests were performed in the perioperative period. Primary end‑point was excessive bleeding (>2.5 ml/kg/h) within first 3 h postoperative. Secondary end‑points included transfusion requirements, re‑exploration rates, intensive care unit and in‑hospital stays. Results: Patients in Group A had excessive bleeding (59% vs. 33%, P = 0.02), higher re‑exploration rates (14% vs. 0%, P < 0.01) and higher rate of blood (41% vs. 14%, P < 0.01) and platelet (14% vs. 2%, P = 0.05) transfusions. On multivariate analysis, preoperative platelet function testing was the most significant predictor of excessive bleeding (odds ratio [OR]: 2.3, P = 0.08), need for blood (OR: 5.5, P < 0.01) and platelet transfusion (OR: 15.1, P < 0.01). Postoperative “ASPI test” best predicted the need for transfusion (sensitivity ‑ 0.86) and excessive blood loss (sensitivity ‑ 0.81). TEG results did not correlate well with any of these outcome measures. Conclusions: Peri‑operative platelet functional assessment with Multiplate® was the strongest predictor for bleeding and transfusion requirements in patients on anti‑platelet therapy until the time of surgery. Study registration: ISRCTN43298975 (http:// www.controlled‑trials.com/ISRCTN43298975/).