International Journal of Hematology

International Journal of Hematology | Vol. 12, No. 6, June 2021 | pp. 41–48
DOI: 10.46882/2021/IJH/000136

Original Article

Title: Evaluation of baseline plasma protein S functional activity as an independent predictor of thromboembolic recurrence in active 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: Massive renal wasting of natural anticoagulant factors establishes a profound hypercoagulable state in nephrotic-range lupus nephritis, yet the clinical utility of functional protein S monitoring remains under-studied. This prospective study evaluated baseline plasma free protein S functional activity in 54 adult patients with active lupus nephritis to track its correlation with serum albumin depletion and 1-year thromboembolic recurrence outcomes. Protein S activity was quantified via chromogenic substrate assays prior to initiating immunosuppressive therapy. Severe protein S activity reduction (< 50.0%) was identified in 31.4% (17 of 54) of the patients. Multivariable Cox proportional hazards analysis revealed that baseline protein S functional activity below 50.0% was an independent predictor of acute deep vein thrombosis or pulmonary embolism within a 12-month follow-up window (hazard ratio = 3.64, P < 0.01). Protein S depression correlated inversely with serum albumin levels (r = -0.62, P < 0.001) and positively with D-dimer concentrations. Screening for functional protein S profiles provides clear prognostic utility, helping identify high-risk autoimmune nephropathy populations requiring early prophylactic anticoagulation.

Keywords: Lupus nephritis, protein S activity, hypercoagulability, albuminuria, thromboembolism

Manuscript Timeline: Received: March 14, 2021; Revised: April 25, 2021; Accepted: May 12, 2021; Published: June 19, 2021

International Journal of Hematology | Vol. 12, No. 8, August 2021 | pp. 57–64
DOI: 10.46882/2021/IJH/000138

Original Article

Title: Evaluation of automated immature reticulocyte fraction and red blood cell fragmentation flags in separating iron deficiency from thrombotic thrombocytopenic purpura

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 thrombotic thrombocytopenic purpura variants. Evaluations were conducted on 125 adult patients presenting with thrombocytopenia and microcytosis, and diagnoses were validated via serum ferritin, ADAMTS13 activity, and manual visual blood film schistocyte counts. Thrombotic thrombocytopenic purpura was confirmed in 50 cases (ADAMTS13 < 10%), while 75 presented with severe iron deficiency. The mean immature reticulocyte fraction was significantly higher in the thrombotic thrombocytopenic purpura cohort compared to the iron-deficient group (0.36 ± 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 92.8% and a specificity of 89.1% 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: May 12, 2021; Revised: June 20, 2021; Accepted: July 09, 2021; Published: August 14, 2021

International Journal of Hematology | Vol. 12, No. 1, January 2021 | pp. 1–8
DOI: 10.46882/2021/IJH/000131

Original Article

Title: Clinical relevance of serum soluble CD163 and ferritin kinetics as early markers of macrophage activation syndrome in adult-onset Still's disease

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

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

Abstract: Macrophage activation syndrome is a severe hyperinflammatory condition characterized by cytopenias, multi-organ dysfunction, and extreme hyperferritinemia. This prospective cohort study evaluated the diagnostic accuracy of monitoring serum soluble CD163 (sCD163) relative to hyperferritinemia kinetics in 36 adult patients with active adult-onset Still's disease suspected of developing macrophage activation syndrome. Serum soluble CD163 levels were quantified using an enzyme-linked immunosorbent assay. Mean serum ferritin concentrations were significantly elevated in patients with confirmed macrophage activation syndrome (16,450 ± 3,400 ng/ml). Soluble CD163 concentrations were also markedly elevated, with a mean value of 16.4 ± 3.8 μg/ml compared to 1.8 ± 0.5 μg/ml in active disease controls without macrophage activation (P < 0.001). Soluble CD163 levels correlated strongly with falling platelet counts and elevated serum triglycerides (r = 0.62, P < 0.01). Receiver operating characteristic curve analysis established that a soluble CD163 threshold above 7.2 μg/ml yielded a diagnostic sensitivity of 91.6% and a specificity of 88.8%. Measuring soluble CD163 serves as a highly specific biomarker for active macrophage activation, helping differentiate this hyperinflammatory storm from typical underlying disease flare-ups.

Keywords: Macrophage activation syndrome, ferritin, soluble CD163, hemophagocytosis, adult-onset Still's disease

Manuscript Timeline: Received: October 12, 2020; Revised: November 18, 2020; Accepted: December 05, 2020; Published: January 14, 2021

International Journal of Hematology | Vol. 12, No. 2, February 2021 | pp. 9–16
DOI: 10.46882/2021/IJH/000132

Original Article

Title: Prevalence and molecular profiles of DNMT3A and IDH2 somatic mutations in adult acute myeloid leukemia 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: Epigenetic dysregulation driven by specific somatic mutations plays a major role in blocking differentiation in acute myeloid leukemia cells. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase 2 (IDH2) gene variations in 64 adult patients with newly diagnosed acute myeloid leukemia. Genomic DNA was isolated from peripheral blood leucocytes, followed by target-enrichment polymerase chain reaction and Sanger sequencing. DNMT3A mutations (predominantly R882) were detected in 25.0% (16 of 64) of the patients, while IDH2 mutations (R140 and R172 variants) occurred in 15.6% (10 of 64). Co-existing mutations in both genes were documented in 6.2% of the cases. Clinical correlation models revealed that patients harboring DNMT3A mutations displayed significantly higher baseline white blood cell counts and an increased prevalence of monocytic differentiation (FAB M4/M5 subtypes) compared to wild-type cohorts (P < 0.05). Conversely, isolated IDH2 mutations correlated with intermediate-risk cytogenetics and normal karyotypes. Screening for these somatic variants provides vital prognostic refinement, helping separate molecularly distinct myeloid sub-clones before initiating targeted differentiation therapies.

Keywords: Acute myeloid leukemia, DNMT3A mutation, IDH2 mutation, DNA methylation, molecular staging

Manuscript Timeline: Received: November 05, 2020; Revised: December 14, 2020; Accepted: January 10, 2020; Published: February 18, 2021

International Journal of Hematology | Vol. 12, No. 3, March 2021 | pp. 17–24
DOI: 10.46882/2021/IJH/000133

Review Article

Title: Targeting the Wnt/beta-catenin Signaling Pathway in Acute Myeloid Leukemia Stem Cells: Mechanisms and Inhibition

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: Quiescent leukemia stem cells escape standard cytotoxic chemotherapy, driving disease relapse and resistance in acute myeloid leukemia. This comprehensive review examines the cellular mechanisms of the evolutionary conserved Wnt/beta-catenin signaling pathway in sustaining leukemia stem cell self-renewal and marrow niche interactions. Accumulation of beta-catenin in the nucleus complexes with TCF/LEF transcription factors, upregulating critical cell-survival and proliferative genes. Traditional intensive chemotherapy regimens fail to eliminate these slow-cycling progenitors. Evolving management models emphasize the therapeutic deployment of small-molecule Wnt/beta-catenin inhibitors. Combining targeted catenin path inhibitors with low-dose cytarabine or hypomethylating backbones has shown clinical efficacy in expanding overall survival in elderly or frail acute myeloid leukemia populations unsuited for standard induction. However, secondary drug resistance can emerge via alternative microenvironmental niche overrides or signaling crosstalk. This review outlines clear biomarker tracking networks, beta-catenin expression monitoring, and combination protocols designed to bypass intrinsic resistance pathways and optimize clonal eradication in myeloid leukemias.

Keywords: Acute myeloid leukemia, leukemia stem cells, Wnt/beta-catenin pathway, molecular inhibitors, clonal resistance

Manuscript Timeline: Received: December 01, 2020; Revised: January 12, 2021; Accepted: February 04, 2021; Published: March 15, 2021

International Journal of Hematology | Vol. 12, No. 11, November 2021 | pp. 81–88
DOI: 10.46882/2021/IJH/000141

Original Article

Title: Clinical features and response kinetics of low-dose azacitidine combined with low-dose cytarabine in elderly patients with myelodysplastic syndromes

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

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

Abstract: High-risk myelodysplastic syndromes in frail elderly patients carry poor prognoses and limited therapeutic options due to intensive treatment toxicities. This prospective study evaluated the safety and clinical response kinetics of a low-dose combination protocol comprising subcutaneous azacitidine (50 mg/m² daily for 5 days) and low-dose cytarabine (10 mg daily for 10 days) in 24 elderly individuals (aged ≥ 70 years) categorized with advanced myelodysplastic variants. Full blood counts, bone marrow cytopenias, and blast percentages were assessed at baseline and every two treatment cycles. Hematological improvement or partial marrow remission was documented in 62.5% (15 of 24) of the patients within a median of three cycles. The mean hemoglobin level rose from 6.8 ± 1.1 g/dl to 10.4 ± 1.2 g/dl by month 6 (P < 0.01), eliminating red blood cell transfusion dependency in 53.3% of responsive individuals. Grade 3 neutropenia occurred in 20.8% of cases but was successfully managed with transient growth factor support without dropping therapy. This low-dose epigenetic combination provides satisfactory disease control, low myelosuppressive profiles, and structural cost-effectiveness, offering an excellent alternative for vulnerable elderly cohorts.

Keywords: Myelodysplastic syndromes, azacitidine, cytarabine, elderly patients, hematological improvement

Manuscript Timeline: Received: August 14, 2021; Revised: September 20, 2021; Accepted: October 12, 2021; Published: November 15, 2021