ISSN 2997-1036
International Journal of Hematology | Vol. 13, No. 4, April 2022 | pp. 25–32
DOI: 10.46882/2022/IJH/000146
Original Article
Title: Evaluation of baseline plasma antithrombin III functional activity as an independent predictor of thromboembolic risk in lupus nephritis
Names of Authors: E. F. Chinedu¹, G. H. Haruna², I. J. Balogun³
Authors’ Affiliations: ¹Department of Haematology, University of Nigeria Teaching Hospital, Enugu, Nigeria; ²Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Nigeria; ³Department of Chemical Pathology, University of Ilorin, Ilorin, Nigeria
Abstract: Nephrotic-range proteinuria in lupus nephritis induces a severe hypercoagulable state due to the heavy urinary loss of natural regulatory elements, but the clinical utility of functional antithrombin III monitoring remains under-studied. This prospective study evaluated baseline plasma antithrombin III functional activity in 54 adult patients with active Class IV lupus nephritis to track its correlation with serum albumin depletion and 1-year thromboembolic complications. Antithrombin III activity was quantified via chromogenic substrate assays prior to starting high-dose immunosuppressive therapy. Severe antithrombin III activity depletion (< 60.0%) was identified in 29.6% (16 of 54) of the patients. Multivariable Cox proportional hazards regression revealed that baseline antithrombin III activity below 60.0% was an independent predictor of acute deep vein thrombosis or pulmonary embolism within a 12-month follow-up window (hazard ratio = 4.12, P < 0.01). Antithrombin III depression correlated strongly with low serum albumin levels (r = -0.68, P < 0.001) and elevated D-dimer values. Screening for functional antithrombin III profiles provides clear prognostic utility, helping identify high-risk autoimmune renal cohorts requiring early prophylactic anticoagulation.
Keywords: Lupus nephritis, antithrombin III, hypercoagulability, albuminuria, thromboembolism
Manuscript Timeline: Received: January 12, 2022; Revised: February 20, 2022; Accepted: March 08, 2022; Published: April 14, 2022
International Journal of Hematology | Vol. 13, No. 6, June 2022 | pp. 41–48
DOI: 10.46882/2022/IJH/000148
Original Article
Title: Evaluation of automated immature reticulocyte fraction and red blood cell fragmentation flags in separating iron deficiency from atypical hemolytic uremic syndrome
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 atypical hemolytic uremic syndrome 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. Atypical hemolytic uremic syndrome was confirmed in 50 cases, while 75 presented with severe iron deficiency anemia. The mean immature reticulocyte fraction was significantly higher in the hemolytic uremic syndrome 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: March 20, 2022; Revised: April 28, 2022; Accepted: May 15, 2022; Published: June 18, 2022
International Journal of Hematology | Vol. 13, No. 1, January 2022 | pp. 1–8
DOI: 10.46882/2022/IJH/000143
Review Article
Title: Structural architecture and target chemical inhibition of the TP53 pathways in therapy-related acute myeloid leukemia
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: Mutations within the tumor suppressor TP53 gene occur frequently in therapy-related acute myeloid leukemia, correlating with complex karyotypes and severe resistance to standard DNA-damaging cytotoxic chemotherapies. This comprehensive review synthesizes the molecular structural architecture of TP53 disruptions, contrasting missense alterations within the DNA-binding domain with complete multi-allelic deletions. These structural modifications impair p53-mediated transcriptional activation of pro-apoptotic elements, allowing highly abnormal myeloid clones to survive and multiply. Traditional anthracycline and cytarabine induction regimens fail to achieve durable remission in over 80% of TP53-mutated cases. Evolving treatment frameworks emphasize small-molecule targeted therapies, including eprenetapopt (APR-246), which acts by restoring standard wild-type confirmation to mutated p53 proteins, and selective MDM2 inhibitors for TP53 wild-type overexpressing variants. Combining these confirmation restoration agents with low-intensity hypomethylating backbones represents a promising frontier for bypassing standard chemoresistance. This review outlines a clear molecular risk assessment checklist, variant allele fraction tracking systems, and clinical management pathways designed to optimize clonal clearance in therapy-related leukemias.
Keywords: Acute myeloid leukemia, TP53 mutation, eprenetapopt, chemoresistance, tumor suppressor pathways
Manuscript Timeline: Received: October 12, 2021; Revised: November 22, 2021; Accepted: December 10, 2021; Published: January 16, 2022
International Journal of Hematology | Vol. 13, No. 5, May 2022 | pp. 33–40
DOI: 10.46882/2022/IJH/000147
Case Report
Title: Spontaneous massive retroperitoneal hemorrhage secondary to acquired Factor X inhibitor development in an elderly patient: Successful resolution with azathioprine
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 coagulation Factor X 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 severe prolongation of both prothrombin time (52.4 seconds) and activated partial thromboplastin time (88.4 seconds). A 1:1 mixing study with normal pooled plasma failed to correct either parameter, indicating a specific common pathway inhibitor. Functional assays confirmed severely depressed Factor X activity (< 1.5%), and a Bethesda assay quantified a Factor X inhibitor titer of 22.0 Bethesda Units. Hemostasis was achieved using prothrombin complex concentrates alongside supportive measures. Subsequent immunosuppressive therapy with oral prednisone paired with azathioprine (100 mg daily) cleared the inhibitor (0 BU) and normalized Factor X activity by week 8. This case demonstrates that acquired common pathway autoantibodies require immediate diagnostic differentiation and multi-modal therapeutic strategies.
Keywords: Acquired factor X inhibitor, retroperitoneal hemorrhage, common pathway, prothrombin complex concentrate, azathioprine
Manuscript Timeline: Received: February 15, 2022; Revised: March 24, 2022; Accepted: April 11, 2022; Published: May 19, 2022
International Journal of Hematology | Vol. 13, No. 9, September 2022 | pp. 65–72
DOI: 10.46882/2022/IJH/000151
Original Article
Title: Serum hepcidin-25 kinetics and iron profiling updates in pregnant women presenting with severe microcytic anemia
Names of Authors: A. I. Ibrahim¹, C. D. Balogun², E. O. Ojo³
Authors’ Affiliations: ¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria; ²Department of Obstetrics and Gynaecology, University of Ilorin, Ilorin, Nigeria; ³Department of Chemical Pathology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
Abstract: Managing microcytic anemia during gestation requires distinct differentiation between absolute nutritional iron depletion and functional iron blockades driven by subclinical inflammatory states. This prospective study evaluated serum hepcidin-25 kinetics, soluble transferrin receptor (sTfR) levels, and total hemoglobin variations in 85 pregnant women in their third trimester presenting with severe microcytosis (MCV < 70 fl). Bioactive serum hepcidin-25 concentrations were quantified via a competitive enzyme-linked immunosorbent assay. Pregnant individuals with true iron deficiency anemia exhibited complete suppression of serum hepcidin-25 levels (< 1.5 ng/ml) paired with marked elevation of soluble transferrin receptor levels. Conversely, a sub-population presenting with concurrent chronic infections demonstrated paradoxically elevated hepcidin-25 concentrations (mean 24.5 ± 4.2 ng/ml) despite low serum iron parameters, reflecting an inflammatory iron trap. Hepcidin levels correlated positively with serum ferritin metrics (r = 0.62, P < 0.001). Integrating quantitative hepcidin-25 evaluations into gestational screening algorithms provides superior diagnostic security, allowing clinicians to bypass ineffective oral iron replenishment steps and identify functional anemia variants requiring targeted anti-inflammatory or intravenous management.
Keywords: Hepcidin-25, pregnancy, iron deficiency anemia, anemia of chronic disease, soluble transferrin receptor
Manuscript Timeline: Received: June 15, 2022; Revised: July 24, 2022; Accepted: August 12, 2022; Published: September 15, 2022
International Journal of Hematology | Vol. 13, No. 8, August 2022 | pp. 57–64
DOI: 10.46882/2022/IJH/000150
Short Communication
Title: Evaluation of automated microcytic cell mathematical indices in predicting latent iron deficiency in volunteer 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 adolescent cohorts deplete growth-associated 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: May 15, 2022; Revised: June 22, 2022; Accepted: July 11, 2022; Published: August 19, 2022