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The article focuses on the first reported case of GATA1-related X-linked thrombocytopenia with co-inherited β-thalassemia trait (XLTT) in a 16-year-old boy. Topics include the role of GATA1 mutations in various hematopoietic disorders, the specific mutation (p.Arg216Gln) affecting GATA1 in this case, and the complexity of the phenotype resulting from the co-inheritance of XLTT and β-thalassemia.

Traumatic Brain Injury (TBI) patients more often than not develop fever within the first few days of their hospitalization. Studies report that causes are variable and according to the pathogenesis, fever may be harmful or protective. The study was conducted to correlate the development of fever with clinical prognosis. Throughout the study spanning 6 months, a total of 98 patients of TBI were included. In the first 48 hours, 54 patients did not develop fever (temperature >37), 20 patients recorded temperatures between 37 and 39; and 24 patients developed high fever (39). On regular temperature monitoring and follow up, it was found that patients developing fever relatively early during hospitalization were more likely to end up with a poor outcome (Glasgow outcome scale 4 to 5). Therefore, fever is independently a predictor of poor prognosis in TBI patients and should be managed diligently in the first few days. [ABSTRACT FROM AUTHOR]

Background: Raised hemoglobin-A2(HbA2) is the diagnostic hallmark of beta-thalassemia trait (βTT). Diagnostic difficulties may arise in HIV-positive patients on antiretroviral therapy (ART). We compared the effect of various antiretroviral drugs on HbA2levels. We attempted to determine which drugs elevate HbA2levels causing a false-positive diagnosis of βTT and correlate the findings with red cell indices.Methods: A retrospective analysis of the records of an antenatal thalassemia screening program was carried out for 78 HIV-positive adults (70 antenatal women and 8 husbands) to study the effect of antiretroviral drugs on HbA2levels. Three had βTT; 20 treatment-naïve subjects constituted controls. The effects of zidovudine (36 cases), stavudine (7 cases), and tenofovir (12 cases) were evaluated. High-performance liquid chromatography was done for HbA2levels. Values of 3.5–3.9% were borderline and ≥ 4% with hypochromic microcytosis was considered to be βTT.Results: Twenty individuals not on ART had normal HbA2%. Three patients had βTT and showed hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on treatment (25.5%) had borderline HbA2values (mean 3.7%): 11 were on a zidovudine-based regimen and 3 on a stavudine-based regimen. One patient on zidovudine had 4.1% HbA2with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a false suspicion of βTT. All patients on tenofovir had normal HbA2. Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and HbA2levels were increased due to antiretroviral drugs zidovudine and stavudine.Conclusion: Treatment-naïve subjects and those on tenofovir showed no effect on HbA2levels compared with zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had borderline elevated HbA2levels, which could lead to a false impression of βTT. [ABSTRACT FROM AUTHOR]

Compound heterozygosity for one of the Hb Lepore mutations and β-thalassemia (β-thal) is a rare cause of non transfusion-dependent thalassemia. We report a 4-year-old boy who presented clinically as homozygous/compound heterozygous β-thal intermedia (β-TI), an impression that was corroborated by the initial hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/β-thal was revealed after parental studies and molecular analyses including β-globin gene sequencing. Our patient highlights the importance of a logical stepwise multi modality approach and the vital importance of parental screening and molecular studies in accurate characterization of complex hemoglobinopathies. Correct diagnosis is especially crucial if pre natal detection is anticipated for future pregnancies. Molecular analyses alone may not compensate for the unavailability of parental testing. This is because the molecular results may be misinterpreted, especially if limited tests are conducted. The infrequent prior reports of this combination from distant parts of the Indian subcontinent suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in isolated families. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study which investigated the application of cation-exchange (CE)-high performance liquid chromatography (HPLC) in the quantification of hemoglobins and its variants. Topics covered include the unpredictable discrepancies of cellulose acetate electrophoresis (CAE) densitometric hemoglobin fraction levels and the disadvantages of using quantitative screening technique in clinical practice.

Genetic work-up of unexplained erythrocytosis that is suspected to be inherited in nature currently requires either laborious exon-by-exon gene panel testing by Sanger sequencing or expensive next-generation sequencing. A high prevalence of Chuvash polycythemia (61%) has been previously reported among north Indian erythrocytosis patients. We assessed PCR-RFLP for VHL c.598C > T mutation as a first-line test in 99 persons with JAK2 V617F-negative, unexplained erythrocytosis. We enrolled two groups: Group A (n = 38) had erythrocytosis patients (n = 33) or their first-degree relatives (n = 5), and, Group B with 61 healthy blood donation volunteers who were deferred after the discovery of unexplained high hemoglobin levels. Detailed history and clinical examination, hemogram, erythropoietin levels and PCR-RFLP for the VHL :c.598C > T;p.R200W mutation were done. In Group A, three (8%) persons aged 9, 13 and 30-years were homozygous for VHL :c.598C > T. Two were heterozygous (parents of a known case of Chuvash polycythemia). None of the Group B subjects had the Chuvash mutation. Erythropoietin levels in group A were low in 5/26 cases (19%) and normal in 18/26 (69%). In Group B, seven (11%) donors had normal values while the remaining 54 (89%) had high erythropoietin levels. Despite a lower frequency (8%) compared to literature, our results suggest that the relatively simpler PCR-RFLP for VHL :c.598C > T mutation may be considered for the initial genetic screening of unexplained, suspected congenital erythrocytosis in regions where Chuvash polycythemia comprises a large proportion of inherited erythrocytosis, after polycythemia vera and common acquired secondary causes are excluded., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01668-9., Competing Interests: Conflict of interestNil for all the authors., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023.)