Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

INTRODUCTION@#ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere.@*METHODS@#150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies.@*RESULTS@#Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups.@*CONCLUSION@#TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

Autoimmune Haemolytic Anaemia: A cross sectional study in a Tertiary Haematological Centre (Anemia Hemolitik Autoimun: Kajian Keratan Lintang di Pusat Hemotologi Tertier) / Jurnal Sains Kesihatan Malaysia

@#Autoimmune haemolytic anaemia (AIHA) is a group of disorders wherein autoantibody causes decompensated acquired haemolysis. There has been no epidemiological study of autoimmune haemolytic anaemia (AIHA) in Malaysia. This study retrospectively analysed the epidemiology of AIHA including Evan’s Syndrome in a Tertiary Haematology Centre in Malaysia. Patients diagnosed with AIHA and Evan’s Syndrome at 18 years old and above between 1 January 1994 to 1 October 2020 at the out-patient Haematology Clinic of Hospital Raja Permaisuri Bainun, Ipoh were selected. Patients’ information was retrieved from the outpatient clinic records. A total of 71 patients were included of which predominantly female. The mean age for both genders were comparable. Ethnic stratification revealed AIHA was higher in Malays followed by Chinese and Indian. Warm AIHA was most prevalent at 40.8%, compared to cold AIHA and Evan’s Syndrome (both 23.9%), and mixed AIHA (11.3%). Primary was more common than secondary AIHA followed by Evan’s Syndrome. Approximately half of the secondary AIHA and secondary Evan’s Syndrome were due to SLE. Overall, 67.6% of patients received corticosteroid only and 28.2% combined with immunosuppressant. Individuals at higher age and females have higher risk of developing AIHA and Evan’s Syndrome. The highest prevalence was seen among the Malay ethnic. Primary warm AIHA is the most common type and majority of Evan’s syndrome are secondary to autoimmune diseases.

Maternal and perinatal outcome of Evan’s syndrome: a 5 years study in a tertiary care centre

Background: Evans syndrome is a rare autoimmune disorder characterized by simultaneous or sequential presence of a positive antiglobulin test, autoimmune haemolytic anemia (AIHA), and immune thrombocytopenia (ITP). It is characterised by frequent exacerbations and remissions within a chronic course. It was first described by Robert Evans in 1951.  Incidence of AIHA is 1 per 75 - 80,000 and ITP is 5.5 /100000 per general adult population.  Incidence of Evans syndrome is 1.8% to 10% of patients with ITP. Objective was to study the maternal and perinatal outcome of women with Evans syndrome (E).Methods: About 4 antenatal mothers were identified with Evans syndrome at St. Johns medical college and hospital, Bengaluru during the study period of 5 years from July 2013-July 2017. They were followed up during their antenatal, intra natal and postnatal period and outcomes were studied. All patients included in the study fulfilled the criteria for Evans syndrome.Results: There were 4 cases of Evans syndrome, with a total number of deliveries of 11859, during this 5 year study. Incidence was 0.09 per 1000 births. All patients presented with bleeding manifestations ranging from mucosal haemorrhage to subarachnoid haemorrhage (SAH) at the time of diagnosis. All patients were on treatment with either 1st or 2nd line of management with corticosteroids/ azathioprine. None had bleeding during pregnancy after the initiation of treatment. Patients had antenatal complications like preeclampsia 25%, IUGR 25%, oligohydraminos 50%, IUD 25%. 2 patients received platelet transfusions intrapartum. None had intrapartum or postpartum haemorrhage. There were no maternal and neonatal mortality.Conclusions: Evans syndrome in pregnancy is a rare condition and requires multi disciplinary approach involving specialists from obstetrics, neonatology, and hematology. Close maternal and fetal surveillance and management during pregnancy is essential to increase the possibility of a favourable pregnancy outcome in these women.

Auto Immune Mixed Haemolytic anaemia: A rare presentation of SLE

Auto Immune Mixed Haemolytic Anaemia (AIHA) is defined as presence of both warm and cold antibodies against patient’s own red blood cells which is diagnosed by monospecific Direct anti-globulin test. Hereby we report a middle-aged women old women who was a known case of hypothyroidism on regular medication, presented with history of fatigability, exercise intolerance and exertional breathlessness of 1 month duration. The patient was subjected for preliminary investigations, which revealed severe anaemia with hemoglobin of 3.6 g% and an increased reticulocyte count of 12% with normal total leukocyte and platelet counts. Peripheral smear revealed anisopoikilocytosis, nucleated RBCs and schistocytes. Biochemical tests for haemolysis was evaluated which showed and elevated LDH levels (780U/L), and a reduced serum haptoglobulin levels. Liver Function test revealed a total bilirubin of 6.8mg/dl with indirect bilirubin of 5.4 mg/dl with normal liver enzymes. Baseline evaluation of Auto immune haemolytic anaemia with coombs test turned out to be positive. Patient was subjected for Mono specific DAT, Indirect Anti-globulin test (IAT) and antibody screening. Mono specific DAT showed both Anti IgG and anti C3 antibodies. IAT test was positive at 4⁰C and negative at 22⁰C and 39⁰C which confirmed that the AIHA was of mixed warm and cold type. On evaluation for connective tissue diseases, patient serum was reactive for ANA and ds-DNA and found to have Systemic Lupus Erythematosus which is a rarity and was responded to corticosteroids.

A study of clinicopathological profile and treatment outcomes in patients with autoimmune hemolytic anaemia

Background: Autoimmune haemolytic anaemia (AIHA) is relatively uncommon condition with grave consequences, if not diagnosed and treated early. The literature on the clinical outcome and response to treatment is relatively scarce. Aim was to study the clinic-pathological profile and the treatment outcomes in patients with AIHA.Methods: Around 25 patients with AIHA attending a tertiary care hospital over a period of one year were included in the study. The patients were divided based on severity of anaemia and etiology. All the patients data were analysed for the demographic data, clinico -pathological findings and the response to treatment. All the patients data were analysed using SPSS software (version 22).Results: Out of 25 patients, 76% were females and 24% were males. Based on severity of anaemia, 60%, 28% and 8% had severe, moderate and mild anaemia. Around 48% of the patients had thrombocytopenia along with anaemia. 8 (32%) and 17 (68%) patients have primary and secondary AIHAs respectively. In our study the commonest cause for the secondary AIHA was Systemic Lupus Erythematosus (SLE) followed by haematological malignancy, primary Sjogrens, Anti-phospholipid antibody (APLA) syndrome, carcinoma colon and Wilsons disease. Hepatosplenomegaly and lymphadenopathy were present in 36% and 4% respectively. Out of 22 (88%) patients on corticosteroid therapy, 15 (60%) patients responded to corticosteroids alone and 6(24%) patients required corticosteroid plus immunosuppressive therapy.Conclusions: AIHA has to be ruled out in all anaemia patients with indirect hyperbilirubinemia and abnormal peripheral smear. Secondary AIHA is more common than primary. Corticosteroids and immunosuppressive agents are the mainstay of treatment of AIHA.

Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches

Major beta thalassemia is a severe form of thalassemia caused by the alteration of two beta globin genes resulting in a defective synthesis of hemoglobin. It is characterized by chronic severe anemia, ineffective erythropoiesis (IE) and iron overload. However although the thransfusion and chelation assosciated constitute the basis of the traitement curently recommended, they do not allow always to control the iron overload induced by pathology and repeated transfusions. Hematopoietic stem cell transplantation (HSCT) has proven to be a definitive treatment for beta thalassemia. However, this procedure is confronted to immunological complications and the small nomber of histocompatible donors. In the face of these therapeutic blocks, much research has been undertaken in recent years leading to the development of a number of promising therapeutic strategies in order to reduce the constraints linked to current chronic treatments, and to move towards an access to healing for all patients. Among other three approaches are envisaged and are in the experimental phase: Gene therapy to restore globin chain imbalance, Improve ineffective erythropoiesis and Improve iron dysregulation. In this article we give a view on the pathophysiology, clinical manifestations, genetic origin of beta-thalassaemia major. The second part presents the therapeutic arsenal currently used, and its limits leading to therapeutic impasse. The last part explores the scientific tracks that present a real therapeutic potential in ?-Thalassemia.

Microangiopatía trombótica en paciente con cáncer de origen desconocido / Thrombotic microangiopathy in a patient with cancer of unknown origin

Resumen La microangiopatía trombótica asociada a cáncer (MTAC) comprende la presencia de anemia hemolítica microangiopática, trombocitopenia y lesión isquémica de órganos en pacientes con neoplasia de origen conocido o desconocido. Su diagnóstico es desafiante pues suele ser confundido con la púrpura trombocitopénica trombótica, que es la causa más frecuente de microangiopatía trombótica en pacientes sanos. La MTAC puede ser manifestación de la neoplasia en sí misma o manifestación de complicación de la quimioterapia, por lo que tiene un pronóstico pobre. A continuación se presenta el caso de una paciente que desarrolló MTAC en el contexto de cáncer metastásico de origen primario desconocido.

Abstract Cancer-associated thrombotic microangiopathy (CATM) consists of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic end organ-damage in patients with a known or unknown primary malignancy. Its diagnosis is challenging, as it is sometimes confused with thrombotic thrombocytopenic purpura, which is the most common cause of thrombotic microangiopathy in healthy patients. CATM can be a manifestation of the malignancy itself or a chemotherapy-related complication, with these patients having a poor prognosis. A case is presented of a patient who developed CATM in the context of metastatic cancer with an unknown primary site.

Anemia hemolítica secundaria a timoma sin miastenia gravis como síndrome paratímico: presentación de un caso / Haemolytic anemia secondary to thymoma without myasthenia gravis as parathymic syndrome: A case report

Describimos el caso de un paciente masculino de 41 años que cursa con cuadro clínico de dolor torácico, astenia y adinamia, con estudios imagenológicos que evidencian masa en mediastino anterior que corresponde a timoma, de acuerdo con el reporte de patología. Además cursa con anemia hemolítica e hipotiroidismo autoinmune, sin miastenia gravis asociada

The case is presented of a 41 year-old male patient with chest pain, asthenia and adynamia. The imaging studies showed a mass in the anterior mediastinum, which according to the pathology report, was a thymoma. Also, the patient also had haemolytic anaemia and autoimmune hypothyroidism, and with no associated myasthenia gravis

Síndrome de Evans y embarazo en la adolescencia: reporte caso y revisión de la literatura / Evans Syndrome and teenage pregnancy: case report and review of the literature

Objetivo: presentar el caso de una gestante adolescente con síndrome de Evans, y hacer una revisión de la literatura respecto a su tratamiento y pronóstico durante el embarazo. Materiales y métodos: se presenta el caso de una paciente adolescente embarazada con síndrome de Evans, manejada en nuestra unidad, ubicada en un hospital de segundo nivel de referencia en Bogotá (Colombia); se describe la historia clínica, su diagnóstico, manejo y desenlace, y se realiza una revisión de la literatura con énfasis en su tratamiento y pronóstico. Se realizó una búsqueda de literatura utilizando las bases de datos Medline vía PubMed, Embase y la Biblioteca Cochrane a mayo de 2016. Las palabras clave utilizadas fueron "anemia hemolítica autoinmune", "trombocitopenia", "síndrome de Evans" y "embarazo", en español o inglés, sin límite por año de publicación. Resultados: se encontraron 79 publicaciones en la búsqueda en Medline y 61 en Embase. De estas, 13 estudios estaban directamente relacionados con el tema. Uno de los artículos corresponde a una revisión sistemática de la literatura y los demás a reportes de caso. Todos los reportes de caso encontrados están incluidos en la revisión sistemática. El síndrome de Evans se debe sospechar cuando se presenta trombocitopenia y hemólisis en la mujer gestante. La patología tiene un curso variable durante el embarazo y amerita un control estricto materno-fetal. Se dispone de alternativas que incluyen el uso de corticoides, gamaglobulina intravenosa y, en algunos casos, el manejo quirúrgico con esplenectomía. Conclusiones: el síndrome de Evans es una patología rara durante la gestación, se requieren más estudios respecto al tratamiento y pronóstico de la enfermedad que permitan guiar su manejo.

Objective: To present the case of a pregnant teenage girl with Evans Syndrome, and to conduct a review of the literature regarding treatment and prognosis during pregnancy. Materials and methods: Case presentation of a pregnant teenage girl with Evans Syndrome managed at our unit in a Level II referral hospital in Bogota, Colombia; description of the clinical history, diagnosis, management and outcome; and review of the literature focusing on treatment and prognosis. A search of the literature was conducted using the Medline database through PubMed, EMBASE and the Cochrane library up to May 2016. The key terms used were "autoimmune haemolytic anaemia", "thrombocytopenia", "Evans Syndrome" and "pregnancy", both in Spanish and English, with no restriction by year of publication. Results: Overall, 79 publications were found in Medline and 61 in EMBASE. Of these, 13 studies related directly to the topic, one was a systematic review of the literature, and the rest were case reports. All the case reports found are included in the systematic review. Evans Syndrome must be suspected when there is thrombocytopenia and haemolysis in the pregnant woman. The course of the disease varies during pregnancy and warrants close maternal and foetal follow-up. Treatment options are available, including steroids, intravenous gamma globulin and, in certain cases, surgical management with splenectomy. Conclusions: Evans Syndrome is a rare disease during pregnancy. Further studies are needed regarding the treatment and prognosis of the disease in order to guide treatment.

Characterization of Bioactive Components of Gossypium barbadense L. with Hematinic Potential in Wister Albino Rats.

Aims: To ascertain the hematinic potential and bioactive compounds in Gossypium barbadense. Place and Duration of Study: Department of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, and Department of Applied Science, College of Science and Technology, Kaduna Polytechnic, Kaduna, Nigeria between February, 2013 and July, 2014. Methodology: Forty eight (48) apparently healthy albino rats weighing (150-200g) were grouped in to seven groups of five rats each. Thirteen rats were used for the G. barbadense toxicity test. Hemolytic anemia was induced using Phenylhydrazine (10mg/kg bw). Different doses (100mg/ml, 200mg/ml, and 400mg/ml) of G. barbadense were administered with periodic evaluation of Haematological indices (Hemoglobin concentration, Packed Cell Volume, Red Blood Cells and reticulocyte count). Bioferon (0.23ml/kg b.w) was used as the standard drug. Synergistic Thin layer Chromatography and Column Chromatography were used to purify the plant extract. Gas Chromatography linked with Mass Spectroscopy (GC-MS) was used in the Characterization of purified fraction. Results: The level of Hb (g/dl) was found to increase in a dose dependent manner (100mg-12.17g/dl, 200mg-12.60g/dl and 400mg-12.87 g/dl), likewise RBC (4.31, 4.41 and 4.72) and PCV (43.35%, 43.49%, 43.65%). Characterization revealed the presence of 19 compounds. Conclusion: G. barbadense resulted in HB, RBC and PCV boost, owing to inherent bioactive component.

Gunthers with haemolytic anaemia extremly rare: A case report.

Congenital erythropoietic porphyria (CEP), also called Gunthers is the rarest of the porphyrias, with a prevalence estimated at 1 in 1,000,000 or less. Only approximately 200 cases of CEP have been reported till now worldwide. CEP affects males and females equally, and occurs in all ethnic groups. Clinically it is a subacute to chronic type of porphyria, defect is expressed in infancy and clinical features such as extreme cutaneous photosensitivity, blistering, scarring, hyper and hypo pigmentation of photo exposed parts. Haemolytic anaemia with splenomegaly and retarded growth may also be present. Due to its rarity we are presenting Congenital erythropoietic porphyria with haemolytic anaemia.

Anemia hemolítica autoinmune postinfección por virus de la hepatitis A: informe de caso / Autoimmune haemolytic anaemia associated to hepatitis A: case report

La anemia hemolítica autoinmune se asocia con una variedad de virus hepatotrópicos, en particular citomegalovirus (CMV), virus del Epstein-Barr y de la hepatitis B. No es frecuente dentro de la historia natural de la hepatitis A, la aparición de anemia hemolítica, y cuando se presenta, generalmente se asocia a deficiencia de glucosa-6-fosfato deshidrogenasa. Presentamos el caso de un paciente de sexo masculino sin hemólisis previa, con astenia e ictericia de dos meses de evolución y hepatomegalia 14 cm por debajo del reborde costal derecho. Los hallazgos en los exámenes de laboratorios mostraron anemia hemolítica con Coombs directo positivo, anticuerpos tipo inmunoglobulina M contra el virus de la hepatitis A positivos, niveles de bilirrubinas 20 veces y aminotrasferasas cuatro veces por arriba del rango normal; con estos datos el paciente fue diagnosticado como hepatitis A complicada con anemia hemolítica y probable hepatitis autoinmune asociada, por lo que se inició manejo con corticoides, alcanzándose mejoría clínica. Resaltamos la importancia de descartar la infección por el virus de la hepatitis A como posible etiología de anemia hemolítica autoinmune.

Rifampicin-induced immune haemolytic anaemia in a patient on daily anti-tuberculosis treatment

Report one case of a 45 years old male patient lived in Hoc Mon district, Ho Chi Minh City, and admitted in November 24th 2004. His tuberculosis (TB) was first diagnosed in the year 2000 and he was received anti-TB drugs with 2SHR/6HE regime at the anti-TB station. During hospitalization, after 10 days of SHRZE regime (SM 1/2g, Rif 300mg PO, INH 200mg PO, PZA 750mg PO, EMB 600mg PO), he experienced fatigue, dyspnea, jaundice, fever of 39 degree C, blood pressure: 8/5cmHg, SpO2 = 90%. Hematological analysis revealed low hemoglobin and Hct levels, and increase of reticulocyte count and white blood cell count; a positive direct Coombs test. Biochemical tests revealed elevated total, direct and indirect bilirubin levels, increased LDH; decreased haptoglobin; LE cell and ANA were all negative. Patient was diagnosed immune haemolytic anemia and was treated by blood transfusion with the same blood group. He discharged at December 17th 2004 with the last diagnosis was recurrent tuberculosis M(+), rifampicin-induced immune haemolytic anemia