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African Journal of Laboratory Medicine 2022Haemoglobinopathies are inherited haemoglobin disorders that result in anaemia characterised by erythrocyte anisopoikilocytosis. Red cell distribution width (RDW)...
BACKGROUND
Haemoglobinopathies are inherited haemoglobin disorders that result in anaemia characterised by erythrocyte anisopoikilocytosis. Red cell distribution width (RDW) measures anisopoikiloytosis and is readily reported by haematology analysers as a complete blood count parameter. The utility of RDW as a diagnostic marker of haemoglobinopathies in Kenya remains undetermined and undocumented.
OBJECTIVE
This study aimed to determine the diagnostic efficacy of RDW in discriminating haemoglobinopathy and haemoglobinopathy-free cases in Kenya.
METHODS
The case-control study used randomly selected haematology analyser outputs for haemoglobinopathy-free (241, 49.4%) and haemoglobinopathy cases (247, 50.1%) aged 1 month to 66 years old tested in the Aga Khan Hospital, Kisumu, and its satellite centres in western Kenya from 01 January 2015 to 31 December 2020. Results were verified using high performance liquid chromatography. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of RDW as a biomarker for sickle cell disease (SCD) and sickle cell trait phenotypes and β-thalassaemia.
RESULTS
The RDW showed diagnostic significance in SCD phenotypes at 21.1 ROC curve coordinate with 67.7% sensitivity, 90.0% specificity, 0.789 accuracy, 70.5% positive predictive validity, 88.8% negative predictive validity, 6.77 positive likelihood ratio, 0.36 negative likelihood ratio and 18.94 (11.4-31.4) odds ratio.
CONCLUSION
An RDW of 21.1% is potentially a predictor of SCD haemoglobin phenotypes and should be included in the haematology screening algorithm as a critical value, above which suspected cases qualify to be investigated for SCD.
PubMed: 35547332
DOI: 10.4102/ajlm.v11i1.1644 -
Frontiers in Neurology 2020CAD encodes a multifunctional enzyme involved in pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing...
CAD encodes a multifunctional enzyme involved in pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing identified CAD compound heterozygous mutations in a new male patient with global developmental delay (DD), refractory epilepsy, and anemia with anisopoikilocytosis. We further reviewed all published cases with CAD deficiency. Five patients were collected from two publications, including three males and two females, and all presented with DD, drug-resistant epilepsy, and anemia with anisopoikilocytosis. Four out of six patients (including the present case) were supplemented with uridine, which led to immediate cessation of seizures, resolved anemia with anisopoikilocytosis, and progress in global development. The other two patients, who were not treated with uridine, died at the ages of 4 and 5 years. In summary, CAD deficiency is probably a treatable neurometabolic disorder.
PubMed: 32117025
DOI: 10.3389/fneur.2020.00064 -
Cureus May 2022An immunocompetent 45-year-old Cuban-American man presented with worsening knee pain and swelling despite antibiotic therapy. On physical examination, the patient was...
An immunocompetent 45-year-old Cuban-American man presented with worsening knee pain and swelling despite antibiotic therapy. On physical examination, the patient was ill-appearing, cachectic, with a protuberant abdomen and massive splenomegaly. In addition, he had a 10 cm area of peripheral hyperemia with central necrosis in the medial left knee that was non-tender and non-fluctuant. Initial lab work demonstrated pancytopenia, hyponatremia, hypoalbuminemia, and anemia of chronic inflammation. Peripheral smear showed microcytic, hypochromic red blood cells with mild anisopoikilocytosis. and leukopenia with slight left shift and metamyelocytes. Bone marrow biopsy demonstrated amastigotes and kinetoplasts within white blood cells and extracellular space consistent with leishmaniasis. Centers for Disease Control and Prevention (CDC) testing with PCR returned positive for . The patient received two courses of amphotericin B lipid complex (ABLC) with a 28-day course of miltefosine, which resulted in clinical improvement. This case illustrates the unique pathology that can affect immigrants and highlights the need to increase health provider awareness of foreign pathologies in areas with large migrant populations.
PubMed: 35774655
DOI: 10.7759/cureus.25442 -
Blood Jan 2018
Topics: Anemia, Megaloblastic; Anemia, Pernicious; Child; Elliptocytosis, Hereditary; Erythrocytes, Abnormal; Female; Hematologic Diseases; Humans; Malabsorption Syndromes; Prognosis; Proteinuria; Vitamin B 12 Deficiency
PubMed: 29301775
DOI: 10.1182/blood-2017-10-809178 -
Cureus Aug 2023While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12...
While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.
PubMed: 37664295
DOI: 10.7759/cureus.42908 -
European Journal of Case Reports in... 2020Isolated congenital asplenia is a rare condition that mostly manifests in the early years, usually due to fatal systemic infections. In this paper, however, we present a...
UNLABELLED
Isolated congenital asplenia is a rare condition that mostly manifests in the early years, usually due to fatal systemic infections. In this paper, however, we present a case of a 36-year-old asymptomatic patient who was referred for suspected hyposplenism, with no history of splenectomy. There were no significant changes on physical examination. Blood analysis revealed leukocytosis and thrombocytosis as well as moderate anisopoikilocytosis and red blood cells with Howell-Jolly bodies. No spleen or other malformations were identified on imaging. Individuals with isolated congenital asplenia have an increased susceptibility to invasive infections and sepsis, with rapid clinical decline and a high mortality rate despite treatment.
LEARNING POINTS
Isolated congenital asplenia is underdiagnosed in adults and should be excluded in patients with Howell-Jolly bodies in a peripheral blood smear, leukocytosis or/and thrombocytosis.Febrile episodes may present initially in these patients with mild symptoms; however, rapid progress to septic shock can occur. As a result, a delay in initiating broad-spectrum antibiotics may compromise their survival.Prevention with an individual vaccination plan and patient education is paramount.
PubMed: 32309250
DOI: 10.12890/2020_001429 -
Journal of Thrombosis and Haemostasis :... Nov 2013GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease.
BACKGROUND
GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease.
METHODS
A family with a novel bleeding disorder was identified and characterized. Genetic linkage analysis and massively parallel sequencing were used to localize the mutation causing the disease phenotype on chromosome 9. Functional studies were then performed in megakaryocytic cell lines to determine the biological effects of the mutant transcript.
RESULTS
We have identified a family with an autosomal dominant bleeding disorder associated with macrothrombocytopenia, red cell anisopoikilocytosis, and platelet dysfunction. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other family members exhibit only abnormal bleeding with surgery. A single nucleotide insertion was identified in GFI1B that predicts a frameshift mutation in the fifth zinc finger DNA-binding domain. This mutation alters the transcriptional activity of the protein, resulting in a reduction in platelet α-granule content and aberrant expression of key platelet proteins.
CONCLUSIONS
GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function.
Topics: Adult; Aged; Aged, 80 and over; Blood Platelet Disorders; Blood Platelets; Erythrocytes; Female; Frameshift Mutation; Genetic Linkage; Humans; Male; Megakaryocytes; Middle Aged; Mutation; Phenotype; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins; Repressor Proteins; Sequence Analysis, DNA; Transfection; Young Adult
PubMed: 23927492
DOI: 10.1111/jth.12368 -
British Journal of Haematology Sep 2020
Topics: Aged; Anaplastic Lymphoma Kinase; Brain Neoplasms; Carbazoles; Erythrocytes; Female; Hemolysis; Humans; Lung Neoplasms; Male; Piperidines; Protein Kinase Inhibitors
PubMed: 32537738
DOI: 10.1111/bjh.16813