International Journal of Hematology

International Journal of Hematology | Vol. 15, No. 5, May 2024 | pp. 33–40
DOI: 10.46882/2024/IJH/000171

Original Article

Title: Serum erythroferrone kinetics and absolute iron utilization markers in pediatric beta-thalassemia major variants

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: Severe ineffective erythropoiesis drives profound hyperferritinemia and systemic iron loading in transfusion-dependent thalassemias, mediated by erythroblast-derived signaling peptides. This prospective clinical study evaluated serum erythroferrone (ERFE) kinetics, circulating hepcidin levels, and soluble transferrin receptor values in 45 pediatric patients presenting with confirmed beta-thalassemia major. Serum biomarker concentrations were quantified utilizing high-sensitivity enzyme-linked immunosorbent assays. Thalassemic children exhibited a five-fold increase in steady-state serum erythroferrone levels (mean 126.4 ± 24.5 pg/ml) compared to healthy controls (P < 0.001). This overproduction of erythroferrone correlated inversely with bioactive plasma hepcidin-25 levels (r = -0.58, P < 0.01), leading to unchecked intestinal iron absorption and toxic macrophage release despite significant tissue iron deposition (ferritin > 1200 ng/ml). Soluble transferrin receptor indices reflected immense marrow erythroid expansion. Tracking erythroferrone kinetics provides an accurate, non-invasive indicator of ineffective erythroid drive and systemic iron loading risk, helping clinicians optimize the timing for initializing iron chelation or therapeutic modulation before severe parenchymal target-organ damage manifests.

Keywords: Beta-thalassemia major, erythroferrone, hepcidin suppression, ineffective erythropoiesis, iron overload

Manuscript Timeline: Received: February 10, 2024; Revised: March 18, 2024; Accepted: April 05, 2024; Published: May 14, 2024

International Journal of Hematology | Vol. 15, No. 11, November 2024 | pp. 81–88
DOI: 10.46882/2024/IJH/000177

Case Report

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

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 high-dose oral prednisone 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: August 18, 2024; Revised: September 25, 2024; Accepted: October 14, 2024; Published: November 15, 2024

International Journal of Hematology | Vol. 15, No. 12, December 2024 | pp. 89–96
DOI: 10.46882/2024/IJH/000178

Original Article

Title: Evaluation of automated immature reticulocyte fraction and red blood cell fragmentation flags in separating iron deficiency from microangiopathic hemolytic anemia variants

Names of Authors: Q. S. Abubakar¹, U. T. Maina²

Authors’ Affiliations: ¹Department of Haematology, National Hospital, Abuja, Nigeria; ²Department of Pathology, Bayero University, Kano, Nigeria

Abstract: Severe microcytic anemia fragments can mimic schistocytes on automated counters, requiring robust laboratory separation parameters to prevent inappropriate therapeutic decisions. This prospective diagnostic study evaluated the performance of automated immature reticulocyte fractions (IRF) and fragmented red blood cell (FRC) flags for separating absolute iron deficiency anemia from microangiopathic hemolytic anemia variants. Evaluations were conducted on 125 adult patients presenting with thrombocytopenia and microcytosis, and diagnoses were validated via serum ferritin, complement functional assays, and manual visual blood film schistocyte counts. Microangiopathic hemolytic anemia was confirmed in 50 cases, while 75 presented with severe iron deficiency anemia. The mean immature reticulocyte fraction was significantly higher in the microangiopathic cohort compared to the iron-deficient group (0.34 ± 0.08 versus 0.12 ± 0.03, P < 0.001), reflecting an intense bone marrow response. Conversely, automated fragmentation flags were elevated in both groups. Receiver operating characteristic analysis established a combined IRF and FRC model that achieved a diagnostic sensitivity of 91.2% and a specificity of 88.4% for identifying true microangiopathic processes. Utilizing automated reticulocyte maturity indices provides an efficient, low-cost asset for screening destructive hemolytic conditions.

Keywords: Immature reticulocyte fraction, fragmented red cells, iron deficiency anemia, schistocytes, cell counter indices

Manuscript Timeline: Received: September 15, 2024; Revised: October 22, 2024; Accepted: November 10, 2024; Published: December 14, 2024

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. 14, No. 6, June 2023 | pp. 41–48
DOI: 10.46882/2023/IJH/000160

Short Communication

Title: Evaluation of automated microcytic cell mathematical indices in predicting latent iron deficiency in volunteer multiparous adolescent blood donors

Names of Authors: B. C. Akpan¹, D. E. Usman²

Authors’ Affiliations: ¹Department of Haematology, University of Calabar, Calabar, Nigeria; ²Department of Clinical Pharmacology, Ahmadu Bello University, Zaria, Nigeria

Abstract: Frequent blood donations in multiparous adolescent cohorts deplete biological iron pools, often inducing latent iron deficiency before total hemoglobin screening tests fall below acceptable thresholds. This diagnostic study evaluated the predictive performance of the Mentzer index and the Green and King mathematical cell counter formulas for identifying latent iron depletion in 120 regular adolescent blood donors presenting with normal total hemoglobin levels (≥ 12.5 g/dl). Calculated indices were cross-validated against biochemical serum ferritin reference parameters. Latent iron deficiency, defined by a serum ferritin below 20 ng/ml, was confirmed in 24.1% (29 of 120) of the donor cohort. The Green and King formula achieved an isolated sensitivity of 89.6% and a positive predictive value of 76.1% for predicting depleted iron reserves, significantly outperforming the Mentzer index model (P < 0.05). Utilizing automated cell counter mathematical formulas offers an efficient, low-cost screening protocol to detect latent iron-restricted erythropoiesis and preserve donor safety.

Keywords: Blood donors, latent iron deficiency, Mentzer index, Green and King formula, donor selection

Manuscript Timeline: Received: March 20, 2023; Revised: April 26, 2023; Accepted: May 15, 2023; Published: June 18, 2023

International Journal of Hematology | Vol. 14, No. 8, August 2023 | pp. 57–64
DOI: 10.46882/2023/IJH/000162

Original Article

Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related clonal hematopoiesis 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 peripheral blood leucocytes, 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. 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 cytopenia, next-generation sequencing

Manuscript Timeline: Received: May 10, 2023; Revised: June 15, 2023; Accepted: July 09, 2023; Published: August 16, 2023