International Journal of Hematology

International Journal of Hematology | Vol. 16, No. 5, May 2025 | pp. 33–40
DOI: 10.46882/2025/IJH/000183

Review Article

Title: Structural mechanics and targeted biochemical inhibition of the menin-KMT2A interaction loops in pediatric acute leukemias

Names of Authors: M. A. Bello¹, O. R. Eze²

Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria

Abstract: Chromosomal translocations involving the lysine methyltransferase 2A (KMT2A) gene drive high-risk leukemic transformations in pediatric populations, characterized by poor clinical outcomes and limited response to standard multi-agent induction. This comprehensive review examines the molecular structural mechanics of the oncogenic KMT2A-fusion protein complex, detailing its mandatory dependence on the small-molecule cofactor menin to sustain high transcription levels of homeobox (HOXA) and MEIS1 target genes. This continuous up-regulation effectively blocks hematopoietic differentiation, locking pediatric myeloblasts or lymphoblasts in proliferative loops. Evolving therapeutic models focus on blocking this binding site using highly selective, small-molecule menin inhibitors like revumenib (SNDX-5613) and ziftomenib. These inhibitors sit directly within the hydrophobic central pocket of menin, disrupting the KMT2A interaction, down-regulating HOXA machinery, and inducing rapid morphologic differentiation. However, secondary drug resistance point mutations within the menin binding pocket present ongoing challenges. This review details structural biomarkers, mutant variant tracking, and clinical combination schedules designed to optimize menin-inhibition and maximize survival outcomes in pediatric KMT2A-rearranged leukemias.

Keywords: Acute leukemia, KMT2A rearrangement, menin inhibitors, revumenib, pediatric oncology

Manuscript Timeline: Received: February 10, 2025; Revised: March 18, 2025; Accepted: April 05, 2025; Published: May 14, 2025

International Journal of Hematology | Vol. 16, No. 7, July 2025 | pp. 49–56
DOI: 10.46882/2025/IJH/000185

Original Article

Title: Screening for lupus anticoagulant using a simplified textrin time and Russell's viper venom time index protocol in unprovoked upper limb deep vein thrombosis

Names of Authors: Y. Z. Ibrahim¹, A. B. Okafor², C. D. Danjuma³

Authors’ Affiliations: ¹Department of Haematology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria; ²Department of Pathology, University of Ibadan, Ibadan, Nigeria; ³Department of Haematology, University of Maiduguri, Maiduguri, Nigeria

Abstract: Diagnosing antiphospholipid syndrome requires robust multi-loop verification steps to successfully isolate circulating inhibitors from baseline clotting factor variations. This prospective diagnostic study evaluated the performance of a combined screening protocol using the textrin time (TT) and the reference dilute Russell’s viper venom time (dRVVT) index loop to detect lupus anticoagulant in 72 adult patients presenting with unprovoked upper limb deep vein thrombosis. Patient plasma matrices underwent sequential 1:1 mixing loops with normal pooled plasma, followed by high-phospholipid corrections to calculate confirmatory ratios. Lupus anticoagulant presence was confirmed in 22.2% (16 of 72) of the thromboembolic cohort. The textrin-dRVVT multi-index protocol achieved a diagnostic sensitivity of 93.7% and a specificity of 91.6% when cross-validated against international standard guidelines. Mixing indexes correlated positively with a history of recurrent pulmonary embolism (r = 0.48, P < 0.05). Notably, the snake venom-based textrin matrix resisted low-molecular-weight heparin or therapeutic warfarin interference, providing an accurate, cost-effective thrombophilia risk-profiling asset for specialized regional clinical pathology laboratories.

Keywords: Lupus anticoagulant, textrin time, diluted Russell’s viper venom time, mixing studies, thrombophilia screening

Manuscript Timeline: Received: April 18, 2025; Revised: May 22, 2025; Accepted: June 10, 2025; Published: July 16, 2025

International Journal of Hematology | Vol. 16, No. 9, September 2025 | pp. 65–72
DOI: 10.46882/2025/IJH/000187

Case Report

Title: Spontaneous massive retroperitoneal hemorrhage secondary to acquired Factor XI inhibitor development in an elderly patient: Eradication with azathioprine and deflazacort

Names of Authors: K. L. Musa¹, M. N. Lawal², O. P. Dikko³

Authors’ Affiliations: ¹Department of Haematology, Federal Medical Centre, Katsina, Nigeria; ²Department of Surgery, Bayero University, Kano, Nigeria; ³Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Abstract: Spontaneous development of neutralizing autoantibodies directed against contact activation pathway components is an exceptionally rare clinical condition that causes catastrophic bleeding events in elderly populations. We report a 74-year-old male who presented with sudden, unprovoked left flank pain, lower abdominal distension, and hypovolemic shock. Abdominal computed tomography confirmed a massive retroperitoneal hematoma measuring 12.4 × 8.5 cm without prior trauma or anticoagulant exposure. Coagulation profiles demonstrated isolated, severe prolongation of activated partial thromboplastin time (92.4 seconds) with a normal prothrombin time. A 1:1 mixing study with normal pooled plasma failed to correct the activated partial thromboplastin time, indicating a specific intrinsic pathway inhibitor. Functional assays confirmed severely depressed Factor XI activity (< 1.5%), and a Bethesda assay quantified a Factor XI inhibitor titer of 18.0 Bethesda Units. Hemostasis was achieved using recombinant activated Factor VII bypassing agents (90 μg/kg every 3 hours) alongside supportive measures. Subsequent immunosuppressive therapy with oral deflazacort paired with azathioprine (100 mg daily) successfully cleared the inhibitor (0 BU) and normalized Factor XI activity by week 8. This case demonstrates that acquired Factor XI autoantibodies require immediate diagnostic differentiation and multi-modal therapeutic strategies.

Keywords: Acquired factor XI inhibitor, retroperitoneal hemorrhage, intrinsic pathway, bypassing agents, azathioprine

Manuscript Timeline: Received: June 15, 2025; Revised: July 24, 2025; Accepted: August 14, 2025; Published: September 15, 2025

International Journal of Hematology | Vol. 16, No. 3, March 2025 | pp. 17–24
DOI: 10.46882/2025/IJH/000181

Original Article

Title: Serum erythroferrone kinetics and absolute iron utilization markers in pediatric beta-thalassemia trait variations

Names of Authors: A. I. Ibrahim¹, C. D. Balogun², E. O. Ojo³

Authors’ Affiliations: ¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria; ²Department of Paediatrics, University of Ilorin, Ilorin, Nigeria; ³Department of Chemical Pathology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria

Abstract: Mild ineffective erythropoiesis occurs in minor hemoglobinopathies, yet the regulatory role of erythroid factors in modulating iron metrics remains unquantified in carrier populations. This prospective clinical study evaluated steady-state serum erythroferrone (ERFE) kinetics, circulating hepcidin levels, and soluble transferrin receptor values in 45 pediatric patients presenting with confirmed beta-thalassemia trait profiles. Serum biomarker concentrations were quantified utilizing high-sensitivity enzyme-linked immunosorbent assays. Children carrying the trait exhibited a two-fold increase in steady-state serum erythroferrone levels (mean 42.6 ± 8.4 pg/ml) compared to healthy controls (P < 0.01). This mild overproduction of erythroferrone correlated with a slight suppression of bioactive plasma hepcidin-25 levels, driving increased intestinal iron extraction. Soluble transferrin receptor indices reflected steady marrow iron demands, while serum ferritin parameters remained within normal reference intervals, excluding iron overload. Tracking erythroferrone kinetics provides an accurate, non-invasive indicator of baseline marrow erythroid activity, helping clinicians differentiate inherited traits from nutritional iron deficiencies without executing expensive genetic mapping loops.

Keywords: Beta-thalassemia trait, erythroferrone, hepcidin modulation, ineffective erythropoiesis, iron utilization

Manuscript Timeline: Received: December 05, 2024; Revised: January 14, 2025; Accepted: February 04, 2025; Published: March 19, 2025

International Journal of Hematology | Vol. 15, No. 8, August 2024 | pp. 57–64
DOI: 10.46882/2024/IJH/000174

Original Article

Title: Impact of systemic hydroxyurea on plasma soluble thrombomodulin levels and microvascular velocity tracking in pediatric sickle cell anemia

Names of Authors: S. T. Adeyemi¹, U. V. Okoye², W. X. Salami³

Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Obafemi Awolowo University, Ile-Ife, Nigeria; ²Department of Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria; ³Department of Paediatrics, Ahmadu Bello University, Zaria, Nigeria

Abstract: Continuous endothelial cell desquamation and low nitric oxide states fuel widespread microvascular shearing and high pulmonary pressures in sickle cell anemia. This prospective cohort study evaluated the long-term impact of optimized hydroxyurea therapy on plasma soluble thrombomodulin (sTM) levels, an index of direct endothelial injury, and tricuspid regurgitant jet velocity (TRJV) shifts in 50 pediatric patients presenting with steady-state sickle cell anemia (HbSS). Hydroxyurea was administered at maximum tolerated doses (15 to 25 mg/kg/day) and monitored over 12 months. Plasma markers were quantified via an enzyme-linked immunosorbent assay, and velocities were tracked using Doppler echocardiography. Baseline mean soluble thrombomodulin levels fell significantly from 14.2 ± 3.8 ng/ml to 6.2 ± 1.1 ng/ml at month 12 (P < 0.001). Concurrently, the proportion of patients presenting with high-risk velocity metrics (TRJV ≥ 2.5 m/s) fell from 36.0% to 14.0%. Thrombomodulin suppression correlated strongly with an increase in fetal hemoglobin from 5.2% to 15.6% and a drop in serum lactate dehydrogenase. These findings confirm that hydroxyurea successfully preserves endothelial integrity, limiting vascular damage and progressive cardiopulmonary remodeling in pediatric sickle cell variants.

Keywords: Sickle cell anemia, hydroxyurea, thrombomodulin, endothelial injury, tricuspid regurgitant jet velocity

Manuscript Timeline: Received: May 12, 2024; Revised: June 20, 2024; Accepted: July 09, 2024; Published: August 14, 2024

International Journal of Hematology | Vol. 15, No. 6, June 2024 | pp. 41–48
DOI: 10.46882/2024/IJH/000172

Original Article

Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related myelodysplastic syndrome variants

Names of Authors: G. M. Babalola¹, I. N. Nwosu², K. S. Abubakar³

Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; ²Department of Medicine, University of Nigeria, Nsukka, Nigeria; ³Department of Pathology, Bayero University, Kano, Nigeria

Abstract: Genotoxic stress from prior cytotoxic regimens selects for chemoresistant stem cell clones harboring specific mutations, expanding the risk of therapy-related myeloid neoplasms. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of protein phosphatase Mn2+/Mg2+ dependent 1D (PPM1D) and tumor suppressor TP53 gene variations in 64 adult lymphoma survivors presenting with persistent, unexplained cytopenias post-chemotherapy. Genomic DNA was isolated from bone marrow aspirates, followed by deep next-generation sequencing assays. PPM1D exon 6 mutations were detected in 14.1% (9 of 64) of the cytopenic survivors, while TP53 variations occurred in 10.9% (7 of 64). Overlapping mutations in both DNA-damage response genes were documented in 3.1% of cases. Clinical phenotype models revealed that sub-clones with PPM1D variants exhibited extreme survival advantages under cisplatin or etoposide exposure, correlating with prolonged neutropenia and progressive marrow dysplasia consistent with therapy-related myelodysplastic syndrome. Screening for these chemoresistant variants provides essential molecular tracking vectors, helping pathologists separate benign marrow suppression from emerging pre-leukemic clonal shifts.

Keywords: Clonal hematopoiesis, PPM1D mutation, TP53 mutation, therapy-related myelodysplastic syndrome, next-generation sequencing

Manuscript Timeline: Received: March 20, 2024; Revised: April 25, 2024; Accepted: May 12, 2024; Published: June 18, 2024