International Journal of Hematology

International Journal of Hematology | Vol. 7, No. 2, February 2016 | pp. 9–16
DOI: 10.46882/2016/IJH/000074

Original Article

Title: Impact of hydroxyurea optimization on transcranial Doppler velocity variations in children with 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: Elevated time-averaged maximum mean velocities on transcranial Doppler (TCD) ultrasonography identify children with sickle cell anemia who carry an exceptionally high risk of primary stroke. This prospective cohort study evaluated the efficacy of optimized hydroxyurea therapy for reducing elevated transcranial Doppler velocities in 54 pediatric patients (aged 2 to 12 years) presenting with conditional (170 to 199 cm/s) or abnormal (≥ 200 cm/s) baseline velocities. Hydroxyurea was initiated at 15 mg/kg/day and titrated to the maximum tolerated dose over 12 months. Repeat transcranial Doppler evaluations were performed at 6 and 12 months. The mean baseline velocity fell significantly from 186.4 ± 12.5 cm/s to 154.2 ± 10.4 cm/s at month 12 (P < 0.001). Concurrently, fetal hemoglobin concentrations rose from a baseline mean of 6.2 ± 1.8% to 16.5 ± 3.2%. None of the children in the conditional or abnormal cohorts progressed to a primary stroke during the study window. Optimizing hydroxyurea to maximum tolerated doses effectively reduces high cerebrovascular blood flow velocities, providing an accessible and non-invasive pharmacological pathway for primary stroke prevention in pediatric sickle cell populations.

Keywords: Sickle cell anemia, hydroxyurea, transcranial Doppler, fetal hemoglobin, pediatric stroke

Manuscript Timeline: Received: November 05, 2015; Revised: December 14, 2015; Accepted: January 08, 2016; Published: February 18, 2016

International Journal of Hematology | Vol. 6, No. 6, June 2015 | pp. 41–48
DOI: 10.46882/2015/IJH/000066

Original Article

Title: Evaluation of baseline plasma fibrinogen levels as a prognostic indicator in acute myeloid leukemia patients

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: Coagulation abnormalities frequently complicate the clinical course of acute myeloid leukemia, yet the prognostic value of baseline fibrinogen remains under-studied. This prospective study evaluated plasma fibrinogen levels in 55 newly diagnosed adult patients with acute myeloid leukemia (excluding acute promyelocytic leukemia) to assess its correlation with induction remission success and 1-year survival outcomes. Fibrinogen was quantified using the Clauss clotting assay before starting standard cytarabine-daunorubicin chemotherapy. Hypofibrinogenemia (< 1.50 g/L) was detected in 14.5% of the patients, while hyperfibrinogenemia (> 4.50 g/L) was present in 21.8%. Multivariate analysis identified baseline hypofibrinogenemia as an independent predictor of early hemorrhagic mortality during induction therapy (odds ratio = 4.12, P < 0.01). Conversely, hyperfibrinogenemia correlated with high white blood cell counts and increased risk of tumor lysis syndrome. Patients with normal baseline fibrinogen levels (1.50 to 4.50 g/L) demonstrated significantly higher 1-year overall survival compared to abnormal cohorts (P < 0.05). Pre-treatment fibrinogen screening provides valuable prognostic utility, helping identify patients at high risk for fatal bleeding or hyperinflammatory reactions during induction regimens.

Keywords: Acute myeloid leukemia, fibrinogen, hypofibrinogenemia, early mortality, prognosis

Manuscript Timeline: Received: March 14, 2015; Revised: April 25, 2015; Accepted: May 12, 2015; Published: June 19, 2015

International Journal of Hematology | Vol. 6, No. 5, May 2015 | pp. 33–40
DOI: 10.46882/2015/IJH/000065

Original Article

Title: Screening for lupus anticoagulant using a simplified kaolin clotting time mixing assay in patients with unexplained arterial 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: Lupus anticoagulant is an important acquired thrombophilic marker linked to arterial strokes and peripheral vascular occlusions. This study evaluated the diagnostic accuracy of a simplified kaolin clotting time (KCT) mixing assay for identifying lupus anticoagulant in 64 adult patients presenting with unexplained, unprovoked arterial thrombosis. Standardized 1:1 and 4:1 mixtures of patient plasma with normal pooled plasma were performed without automated phospholipid reagents, and results were compared with reference diluted Russell’s viper venom time guidelines. Lupus anticoagulant was confirmed in 21.8% (14 of 64) of the patients using reference indexes. The simplified kaolin clotting time mixing protocol demonstrated a sensitivity of 85.7% and a specificity of 88.0% for identifying lupus anticoagulant presence. Kaolin clotting time prolongation indices correlated with the severity of thrombotic recurrence rates (r = 0.42, P < 0.05). While less sensitive than Russell's venom test for heparin-containing matrices, the simplified kaolin clotting method provides an inexpensive, reproducible diagnostic alternative for baseline thrombophilia screening in resource-limited settings.

Keywords: Lupus anticoagulant, kaolin clotting time, mixing studies, arterial thrombosis, antiphospholipid antibodies

Manuscript Timeline: Received: February 12, 2015; Revised: March 20, 2015; Accepted: April 05, 2015; Published: May 15, 2015

International Journal of Hematology | Vol. 6, No. 10, October 2015 | pp. 73–80
DOI: 10.46882/2015/IJH/000070

Short Communication

Title: Screening for alpha-thalassemia trait using red blood cell distribution width ratios in microcytic 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: Differentiating benign inherited microcytosis from iron deficiency in blood donors is essential to prevent inappropriate donor deferrals or unnecessary iron treatments. This diagnostic study evaluated the screening performance of the red blood cell distribution width (RDW) index and the Mentzer formula for identifying alpha-thalassemia trait in 110 healthy blood donors presenting with isolated microcytosis (MCV < 75 fl) and normal iron panels. Molecular multiplex PCR served as the confirmatory standard for identifying alpha-gene deletions (-alpha³.⁷). Alpha-thalassemia trait was confirmed in 22.7% (25 of 110) of the microcytic donors. Confirmed thalassemia carriers exhibited a significantly narrower red blood cell distribution width range (12.8 ± 0.9%) compared to donors with latent iron depletion (16.4 ± 1.5%, P < 0.001). An RDW value below 14.0% combined with a Mentzer index below 13 achieved a sensitivity of 88.0% and a specificity of 84.7% for predicting alpha-thalassemia deletions. Utilizing automated cell counter RDW ratios offers an accessible, low-cost screening protocol to detect hemoglobin gene traits during routine blood donor assessments.

Keywords: Alpha-thalassemia trait, blood donors, microcytosis, red blood cell distribution width, Mentzer index

Manuscript Timeline: Received: July 20, 2015; Revised: August 25, 2015; Accepted: September 14, 2015; Published: October 18, 2015

International Journal of Hematology | Vol. 6, No. 3, March 2015 | pp. 17–24
DOI: 10.46882/2015/IJH/000063

Review Article

Title: Evolving mechanisms of drug resistance to hypomethylating agents in myelodysplastic syndromes management

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: Hypomethylating agents like azacitidine and decitabine have changed the therapeutic management of high-risk myelodysplastic syndromes, yet primary or secondary drug resistance eventually develops in most patients. This review synthesizes current insights into the cellular and molecular mechanisms driving this resistance, focusing on altered drug transport kinetics, down-regulated cytidine deaminase activation pathways, and mutations in DNA methyltransferase enzymes (DNMT3A). Clonal evolution studies demonstrate that under therapeutic selection, myelodysplastic subclones harboring mutations in TP53, ASXL1, or RUNX1 expand rapidly, promoting resistance and accelerated transformation to acute myeloid leukemia. Additionally, the bone marrow microenvironment protects malignant cells via cytokine signaling cascades and immune checkpoint upregulation (PD-L1). Managing hypomethylating agent failure is a major clinical challenge due to limited second-line choices. Evolving combination regimens that pair hypomethylating backbones with histone deacetylase inhibitors, BCL-2 inhibitors (venetoclax), or targeted immunotherapies offer a promising way to overcome epigenetic resistance mechanisms and improve clinical survival.

Keywords: Myelodysplastic syndromes, hypomethylating agents, azacitidine, drug resistance, clonal evolution

Manuscript Timeline: Received: December 11, 2014; Revised: January 20, 2015; Accepted: February 12, 2015; Published: March 19, 2015.

International Journal of Hematology | Vol. 6, No. 2, February 2015 | pp. 9–16
DOI: 10.46882/2015/IJH/000062

Original Article

Title: Prevalence and molecular categorization of BCR-ABL1 transcript types in adult chronic myeloid leukemia patients

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: Characterizing the baseline BCR-ABL1 fusion transcript type in chronic myeloid leukemia is essential for selecting appropriate primers for quantitative molecular monitoring. This cross-sectional study investigated the prevalence and distribution of specific BCR-ABL1 transcript variations in 84 adult patients with newly diagnosed, Philadelphia chromosome-positive chronic myeloid leukemia. Total RNA was extracted from peripheral blood leucocytes, followed by qualitative multiplex reverse transcription polymerase chain reaction. The major BCR-ABL1 transcript (p210) was detected in 95.2% (80 of 84) of the patients. Among the p210 positive cohort, the b3a2 (e14a2) splice variant was the most common, occurring in 56.2% of cases, followed by the b2a2 (e13a2) variant in 38.8%, while 5.0% of patients co-expressed both variants. Rare transcript types, including the p190 (e1a2) micro-transcript, were identified in 4.8% of cases, primarily correlating with a more monomyelocytic phenotype. Patients with the b3a2 transcript variation demonstrated a higher mean baseline platelet count compared to b2a2 cohorts (642 × 10⁹/L versus 412 × 10⁹/L, P < 0.05). Multiplex reverse transcription PCR remains a vital initial diagnostic tool to establish transcript architecture before transitioning to quantitative real-time monitoring pathways.

Keywords: Chronic myeloid leukemia, BCR-ABL1 transcript, splice variants, polymerase chain reaction, molecular epidemiology

Manuscript Timeline: Received: November 05, 2014; Revised: December 14, 2014; Accepted: January 08, 2015; Published: February 17, 2015