International Journal of Hematology

International Journal of Hematology | Vol. 11, No. 6, June 2020 | pp. 41–48
DOI: 10.46882/2020/IJH/000126

Original Article

Title: Evaluation of baseline plasma protein C functional activity as an independent predictor of thromboembolic recurrence in active nephrotic syndrome

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 disease, yet the clinical utility of functional protein C monitoring remains under-studied. This prospective study evaluated baseline plasma free protein C functional activity in 54 adult patients with active nephrotic syndrome to track its correlation with serum albumin depletion and 1-year thromboembolic recurrence outcomes. Protein C activity was quantified via chromogenic substrate assays prior to initiating immunosuppressive therapy. Severe protein C activity reduction (< 55.0%) was identified in 29.6% (16 of 54) of the nephrotic patients. Multivariable Cox proportional hazards analysis revealed that baseline protein C functional activity below 55.0% was an independent predictor of acute deep vein thrombosis or pulmonary embolism within a 12-month follow-up window (hazard ratio = 3.84, P < 0.01). Protein C depression correlated inversely with serum albumin levels (r = -0.65, P < 0.001) and positively with D-dimer concentrations. Screening for functional protein C profiles provides clear prognostic utility, helping identify high-risk nephrotic populations requiring early prophylactic anticoagulation.

Keywords: Nephrotic syndrome, protein C activity, hypercoagulability, albuminuria, thromboembolism

Manuscript Timeline: Received: March 14, 2020; Revised: April 25, 2020; Accepted: May 12, 2020; Published: June 19, 2020

International Journal of Hematology | Vol. 11, No. 7, July 2020 | pp. 49–56
DOI: 10.46882/2020/IJH/000127

Case Report

Title: Spontaneous massive retroperitoneal hemorrhage secondary to acquired Factor VII inhibitor development in an elderly patient: Eradication with cyclosporine

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 VII 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 prothrombin time (52.4 seconds) with a normal activated partial thromboplastin time. A 1:1 mixing study with normal pooled plasma failed to correct the prothrombin time, indicating a specific extrinsic pathway inhibitor. Functional assays confirmed severely depressed Factor VII activity (< 1.0%), and a Bethesda assay quantified a Factor VII inhibitor titer of 24.5 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 prednisone paired with cyclosporine-A (3 mg/kg/day) cleared the inhibitor (0 BU) by week 8. This case demonstrates that acquired Factor VII autoantibodies can cause life-threatening retroperitoneal bleeding, requiring immediate diagnostic differentiation and multi-modal therapeutic strategies.

Keywords: Acquired factor VII inhibitor, retroperitoneal hemorrhage, extrinsic pathway, bypassing agents, cyclosporine

Manuscript Timeline: Received: April 18, 2020; Revised: May 22, 2020; Accepted: June 10, 2020; Published: July 16, 2020

International Journal of Hematology | Vol. 11, No. 8, August 2020 | pp. 57–64
DOI: 10.46882/2020/IJH/000128

Original Article

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

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 and manual visual blood film schistocyte counts. Microangiopathic hemolysis (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome) was confirmed in 50 cases, while 75 presented with severe iron deficiency. The mean immature reticulocyte fraction was significantly higher in the microangiopathic anemia 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: May 12, 2020; Revised: June 20, 2020; Accepted: July 09, 2020; Published: August 14, 2020

International Journal of Hematology | Vol. 11, No. 1, January 2020 | pp. 1–8
DOI: 10.46882/2020/IJH/000121

Original Article

Title: Clinical relevance of serum soluble CD14 and ferritin kinetics as early markers of macrophage activation syndrome in systemic juvenile idiopathic arthritis

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: Macrophage activation syndrome is a hyperinflammatory, life-threatening complication of systemic autoimmune conditions characterized by cytopenias, multi-organ failure, and extreme hyperferritinemia. This prospective cohort study evaluated the diagnostic accuracy of monitoring serum soluble CD14 (sCD14) relative to hyperferritinemia kinetics in 36 pediatric patients with active systemic juvenile idiopathic arthritis suspected of developing macrophage activation syndrome. Serum soluble CD14 levels were quantified using a standardized enzyme-linked immunosorbent assay. Mean serum ferritin concentrations were significantly elevated in patients with confirmed macrophage activation syndrome (18,450 ± 4,200 ng/ml). Soluble CD14 concentrations were also markedly elevated, with a mean value of 14.6 ± 3.2 μg/ml compared to 2.1 ± 0.5 μg/ml in active disease controls without macrophage activation (P < 0.001). Soluble CD14 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 CD14 threshold above 6.8 μg/ml yielded a diagnostic sensitivity of 91.6% and a specificity of 88.8%. Measuring soluble CD14 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 CD14, hemophagocytosis, juvenile idiopathic arthritis

Manuscript Timeline: Received: October 14, 2019; Revised: November 20, 2019; Accepted: December 08, 2019; Published: January 14, 2020

International Journal of Hematology | Vol. 11, No. 2, February 2020 | pp. 9–16
DOI: 10.46882/2020/IJH/000122

Original Article

Title: Prevalence and molecular profiles of DNMT3A and IDH1 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 1 (IDH1) 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 23.4% (15 of 64) of the patients, while IDH1 mutations (R132 variants) occurred in 14.1% (9 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 IDH1 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, IDH1 mutation, DNA methylation, molecular staging

Manuscript Timeline: Received: November 05, 2019; Revised: December 14, 2019; Accepted: January 10, 2020; Published: February 18, 2020

International Journal of Hematology | Vol. 11, No. 3, March 2020 | pp. 17–24
DOI: 10.46882/2020/IJH/000123

Review Article

Title: Cellular mechanisms and targeted molecular inhibition of the hedgehog signaling pathway in acute myeloid leukemia stem cells

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 Hedgehog signaling pathway in sustaining leukemia stem cell self-renewal and marrow niche interactions. Binding of Hedgehog ligands to Patched receptors relieves inhibition on Smoothened (SMO), triggering downstream activation of GLI transcription factors and upregulating cell-survival pathways. Traditional intensive chemotherapy regimens fail to eliminate these slow-cycling progenitors. Evolving management models emphasize the therapeutic deployment of small-molecule Smoothened inhibitors, such as glasdegib. Combining glasdegib 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 novel Smoothened mutations or crosstalk with the bone marrow microenvironment. This review outlines clear biomarker tracking networks, GLI 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, hedgehog pathway, glasdegib, smoothened inhibitor

Manuscript Timeline: Received: December 01, 2019; Revised: January 12, 2020; Accepted: February 04, 2020; Published: March 15, 2020