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Introduction: Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty. Aim: We aimed to evaluate the genetic changes in Indian HA‐patients that are associated with the development of inhibitors. Methods: All HA‐patients with inhibitors who availed coagulation‐laboratory services from January‐2015 till December‐2021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity‐matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse‐shifting‐PCR. Inversion‐negative patients were further assessed by targeted NGS, MLPA. Results: Thirty HA‐patients with inhibitors were identified. All had severe‐HA. Thirty severe‐HA‐patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion‐negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion‐negative patients with and without inhibitors. Seven novel‐variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor‐positive patients, and one frameshift variant in inhibitor‐negative patient. After adjusting for clinical risk‐factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41‐56.3)]. Conclusion: Intron 22 inversions are the commonest variant in Indian patients with severe‐HA. Large deletions predispose to inhibitor development independent of clinical risk factors. [ABSTRACT FROM AUTHOR]

Amoebic liver abscess is the most common extra-intestinal manifestation of amoebiasis. It usually responds well to treatment with metronidazole together with drainage, if indicated. Uncommonly, the abscess may rupture into the pleura, peritoneum or pericardium, bile duct at its hilum, or produce septic emboli. We present a patient with two rare complications: venous thrombosis and jaundice secondary to bilhaemia. [ABSTRACT FROM AUTHOR]

Abstract: BCR∷ABL1 translocation and JAK2V617F mutations are canonical variants of myeloproliferative neoplasms (MPNs). Traditionally considered mutually exclusive, they may rarely coexist. We report the clinicopathological profile and treatment outcomes of four MPN patients with coexistence of these disease-defining genetic variants. Both mutations were detected simultaneously in three patients who did not harbor tell-tale signs of CML and were evaluated for both BCR∷ABL1 and JAK2V617F based on clues from hemogram, peripheral-blood and bone-marrow examination. All were treated with imatinib and hydroxyurea and attained major molecular response after 2-7 months. In another patient, JAK2V617F was detected 15 years after the diagnosis of CML at the time of evaluation of loss of hematological and molecular response. She was treated with dasatinib but no hematologic or molecular response was attained after 6 months despite good compliance. In conclusion, BCR∷ABL1 and JAK2V617F may rarely coexist in MPN with variable temporal evolution, clinicopathological profile, and treatment response., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)