International Journal of Hematology

International Journal of Hematology | Vol. 10, No. 5, May 2019 | pp. 33–40
DOI: 10.46882/2019/IJH/000113

Review Article

Title: Structural biology and targeted biochemical inhibition of IDH1 and IDH2 mutations in acute myeloid leukemia 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: Somatic mutations within the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes create neomorphic enzymatic activities that alter cellular differentiation pathways in acute myeloid leukemia. This comprehensive review synthesizes current insights into the structural structural biology of these variants, highlighting how point mutations at key arginine residues (IDH1 R132, IDH2 R140/R172) drive the abnormal reduction of alpha-ketoglutarate into the oncometabolite 2-hydroxyglutarate (2-HG). The accumulation of 2-hydroxyglutarate competitively inhibits alpha-ketoglutarate-dependent dioxygenases, driving widespread DNA hypermethylation and blocking myeloid progenitor maturation. Evolving management models highlight small-molecule targeted inhibitors, including ivosidenib (AG-120) for IDH1 and enasidenib (AG-221) for IDH2. These agents bind to the allosteric pockets of mutant dimers, suppressing oncometabolite production and releasing the differentiation block without inducing cytotoxic marrow aplasia. However, treatment can precipitate differentiation syndrome, requiring swift corticosteroid protocols. This review outlines clear biomarker tracking systems, 2-hydroxyglutarate clearance monitoring, and combination schedules designed to bypass resistance and optimize outcomes in IDH-mutated myeloid leukemias.

Keywords: Acute myeloid leukemia, IDH1 mutation, IDH2 mutation, 2-hydroxyglutarate, differentiation therapy

Manuscript Timeline: Received: February 12, 2019; Revised: March 22, 2019; Accepted: April 10, 2019; Published: May 18, 2019

International Journal of Hematology | Vol. 10, No. 9, September 2019 | pp. 65–72
DOI: 10.46882/2019/IJH/000117

Case Report

Title: Acquired Factor V inhibitor development presenting with spontaneous massive retroperitoneal hemorrhage in an elderly patient: Successful resolution with plasma exchange and cyclophosphamide

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 V is an exceptionally rare 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 concurrent 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 common pathway inhibitor. Functional assays confirmed severely depressed Factor V activity (< 1.0%), and a Bethesda assay quantified a Factor V inhibitor titer of 24.5 Bethesda Units. Hemostasis was achieved using therapeutic plasma exchange to reduce inhibitor concentrations, combined with prothrombin complex concentrates. Subsequent immunosuppressive therapy with oral prednisone paired with cyclophosphamide (2 mg/kg/day) cleared the inhibitor (0 BU) by week 8. This case demonstrates that acquired Factor V autoantibodies can cause life-threatening retroperitoneal bleeding, requiring immediate diagnostic differentiation and multi-modal therapeutic strategies.

Keywords: Acquired factor V inhibitor, retroperitoneal hemorrhage, common pathway, plasma exchange, cyclophosphamide

Manuscript Timeline: Received: June 18, 2019; Revised: July 28, 2019; Accepted: August 14, 2019; Published: September 15, 2019

International Journal of Hematology | Vol. 9, No. 10, October 2018 | pp. 73–80
DOI: 10.46882/2018/IJH/000106

Original Article

Title: Evaluation of baseline plasma protein S functional activity variations as a predictor of thromboembolic recurrence in 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 urinary loss of low-molecular-weight regulatory proteins creates a severe hypercoagulable state in nephrotic disease, yet the clinical utility of functional protein S monitoring remains under-analyzed. This prospective study evaluated baseline plasma free protein S 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 S activity was quantified using a clotting assay based on factor Xa inhibition prior to initiating corticosteroid regimens. Severe protein S activity reduction (< 50.0%) was identified in 31.4% (17 of 54) of the nephrotic 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 = 3.84, P < 0.01). Furthermore, protein S depression correlated inversely with serum albumin levels (r = -0.65, P < 0.001) and positively with D-dimer concentrations. Screening for functional protein S activity provides clear prognostic utility, helping identify high-risk nephrotic patients who may benefit from early prophylactic anticoagulation.

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

Manuscript Timeline: Received: July 20, 2018; Revised: August 25, 2018; Accepted: September 12, 2018; Published: October 14, 2018

International Journal of Hematology | Vol. 9, No. 9, September 2018 | pp. 65–72
DOI: 10.46882/2018/IJH/000105

Original Article

Title: Screening for lupus anticoagulant using an integrated dRVVT and dilute Russell's viper venom clotting time mix protocol in patients with unprovoked lower limb venous 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: Phospholipid-dependent autoantibodies require precise laboratory confirmation parameters to differentiate circulating anticoagulants from coagulation factor deficiencies. This prospective diagnostic study evaluated the performance of an integrated dilute Russell’s viper venom time (dRVVT) screening and confirmation mix protocol in 70 adult patients presenting with acute, unprovoked lower limb deep vein thrombosis. Patient plasma underwent initial 1:1 mixing steps with normal pooled plasma to exclude simple factor deficiencies, followed by high-phospholipid corrections to calculate confirmatory ratios. Lupus anticoagulant presence was confirmed in 22.8% (16 of 70) of the thromboembolic cohort. The integrated mix-confirmation protocol achieved a diagnostic sensitivity of 93.7% and a specificity of 90.7% when cross-validated against standard international guidelines. Mixing indexes correlated positively with a history of recurrent thrombotic episodes (r = 0.48, P < 0.05). Utilizing this integrated mix loop reduces false-positive results caused by baseline variations in clotting factors, providing a cost-effective and accurate thrombophilia risk-profiling asset for specialized clinical pathology laboratories.

Keywords: Lupus anticoagulant, diluted Russell’s viper venom time, mixing studies, venous thrombosis, thrombophilia screening

Manuscript Timeline: Received: June 14, 2018; Revised: July 22, 2018; Accepted: August 11, 2018; Published: September 15, 2018

International Journal of Hematology | Vol. 9, No. 1, January 2018 | pp. 1–8
DOI: 10.46882/2018/IJH/000097

Case Report

Title: Acquired pure white cell aplasia associated with chronic large granular lymphocytic leukemia: Successful resolution with low-dose methotrexate

Names of Authors: K. L. Musa¹, M. N. Lawal², O. P. Dikko³

Authors’ Affiliations: ¹Department of Haematology, Federal Medical Centre, Katsina, Nigeria; ²Department of Medicine, Bayero University, Kano, Nigeria; ³Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Abstract: Acquired pure white cell aplasia is an exceptionally rare bone marrow failure syndrome characterized by an absolute absence of granulocytic precursors with preserved erythropoiesis and megakaryopoiesis. We report a 58-year-old female presenting with recurrent, severe soft tissue infections, a total white blood cell count of 0.8 × 10⁹/L, and an absolute neutrophil count of 0.0 × 10⁹/L lasting 4 weeks. Bone marrow aspirate and trephine biopsy examinations confirmed a complete lack of myeloid maturation past the myeloblast stage. Flow cytometric analysis of peripheral blood lymphocytes identified a clonal expansion of T-cell large granular lymphocytes co-expressing CD3, CD8, and CD57, confirming an underlying large granular lymphocytic leukemia. Immunomodulatory therapy utilizing low-dose oral methotrexate (10 mg weekly) was initiated. Granulopoietic recovery commenced by week 4, achieving sustained normalization of the absolute neutrophil count (2.4 × 10⁹/L) by month 3 of therapy. The patient remained infection-free and in complete hematological remission at a 12-month follow-up. This case demonstrates that low-dose methotrexate effectively suppresses the auto-reactive cytotoxic clones driving myeloid arrest.

Keywords: Pure white cell aplasia, large granular lymphocytic leukemia, agranulocytosis, methotrexate, marrow failure

Manuscript Timeline: Received: October 18, 2017; Revised: November 25, 2017; Accepted: December 14, 2017; Published: January 18, 2018

International Journal of Hematology | Vol. 9, No. 6, June 2018 | pp. 41–48
DOI: 10.46882/2018/IJH/000102

Original Article

Title: Prevalence and molecular profiles of ASXL1 and TET2 somatic mutations in chronic myelomonocytic 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: Chronic myelomonocytic leukemia combines myelodysplastic and myeloproliferative features, driven by distinct genetic alterations that influence its progression risk. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of additional sex combs-like 1 (ASXL1) and ten-eleven translocation 2 (TET2) alterations in 42 adult patients with confirmed chronic myelomonocytic leukemia. Genomic DNA was isolated from peripheral blood leucocytes, followed by target-enrichment polymerase chain reaction and Sanger sequencing. TET2 mutations were detected in 45.2% (19 of 42) of the patients, while ASXL1 mutations occurred in 38.1% (16 of 42). Co-existing mutations in both genes were documented in 14.2% of the cases. Clinical correlation models revealed that patients harboring ASXL1 mutations displayed significantly higher baseline white blood cell counts (mean 28.4 × 10⁹/L versus 8.6 × 10⁹/L, P < 0.01) and an increased prevalence of severe splenomegaly, consistent with a dominant myeloproliferative variant (CMML-2). Conversely, isolated TET2 mutations correlated with a lower rate of acute transformation over a 12-month observation window. Screening for these somatic variants provides vital prognostic refinement, helping separate aggressive proliferative subtypes from indolent myelodysplastic chronic monocytosis.

Keywords: Chronic myelomonocytic leukemia, ASXL1 mutation, TET2 mutation, clonal hematopoiesis, molecular staging

Manuscript Timeline: Received: March 12, 2018; Revised: April 20, 2018; Accepted: May 10, 2018; Published: June 19, 2018