International Journal of Hematology

International Journal of Hematology | Vol. 10, No. 8, August 2019 | pp. 57–64
DOI: 10.46882/2019/IJH/000116

Original Article

Title: Evaluation of baseline plasma protein C functional activity variations as an independent predictor of recurrent macrovascular thrombosis 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: Excessive renal loss of anticoagulant regulatory elements establishes a profound hypercoagulable state in nephrotic disease, but the predictive utility of functional protein C monitoring remains under-analyzed. This prospective study evaluated baseline plasma free protein C functional activity in 54 adult patients with active nephrotic syndrome to track correlations with serum albumin depletion and 1-year thrombotic recurrence outcomes. Protein C activity was quantified via chromogenic substrate assays prior to initiating standard 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 observation 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: May 12, 2019; Revised: June 20, 2019; Accepted: July 10, 2019; Published: August 17, 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. 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. 11, No. 9, September 2020 | pp. 65–72
DOI: 10.46882/2020/IJH/000129

Original Article

Title: Immunophenotypic profile and clinical stage stratification of B-cell chronic lymphoproliferative disorders utilizing CD200 and CD148 expression markers

Names of Authors: W. A. Adebayo¹, X. Y. Emeka², Z. Z. Salami³

Authors’ Affiliations: ¹Department of Haematology, University of Ibadan, Ibadan, Nigeria; ²Department of Haematology, University of Calabar Teaching Hospital, Calabar, Nigeria; ³Department of Pathology, Lagos University Teaching Hospital, Lagos, Nigeria

Abstract: Multiparameter flow cytometry immunophenotyping plays an important role in separating overlapping mature B-cell malignancies. This prospective study evaluated the diagnostic performance of combining CD200 and CD148 markers to differentiate chronic lymphocytic leukemia from mantle cell lymphoma and marginal zone lymphoma in 55 adult patients presenting with persistent absolute lymphocytosis. Lineage markers and monoclonal light chain restriction were established using flow cytometry. Chronic lymphocytic leukemia was confirmed in 38 cases, while 17 were diagnosed with non-CLL mature B-cell variants. Strong, uniform surface expression of CD200 paired with dim CD148 was detected in 94.7% (36 of 38) of the chronic lymphocytic leukemia cases. In contrast, mantle cell lymphoma cohorts demonstrated a complete absence of CD200 alongside bright CD148 and bright CD20 expression (P < 0.001). Marginal zone lymphoma variants exhibited positive CD148 paired with negative or dim CD200 parameters. High expression density for CD200 correlated with early clinical presentation (Binet Stage A). Incorporating CD200 and CD148 into standard screening protocols provides excellent diagnostic specificity, reducing borderline scores and helping classify mature B-cell expansions.

Keywords: Chronic lymphocytic leukemia, CD200, CD148, flow cytometry, lymphoproliferative disorders, immunophenotyping

Manuscript Timeline: Received: June 15, 2020; Revised: July 24, 2020; Accepted: August 12, 2020; Published: September 15, 2020

International Journal of Hematology | Vol. 10, No. 1, January 2019 | pp. 1–8
DOI: 10.46882/2019/IJH/000109

Original Article

Title: Immunophenotypic profile and clinical stage classification of mature B-cell malignancies utilizing CD200 and CD160 expression variations

Names of Authors: W. A. Adebayo¹, X. Y. Emeka², Z. Z. Salami³

Authors’ Affiliations: ¹Department of Haematology, University of Ibadan, Ibadan, Nigeria; ²Department of Haematology, University of Calabar Teaching Hospital, Calabar, Nigeria; ³Department of Pathology, Lagos University Teaching Hospital, Lagos, Nigeria

Abstract: Multi-color flow cytometry panels play an important role in separating overlapping mature B-cell lymphoproliferative disorders. This prospective study evaluated the diagnostic performance of combining CD200 and CD160 markers to differentiate chronic lymphocytic leukemia from splenic marginal zone lymphoma and hairy cell leukemia in 55 adult patients presenting with persistent absolute lymphocytosis. Lineage markers and monoclonal light chain restriction were established using flow cytometry. Chronic lymphocytic leukemia was confirmed in 38 cases, while 17 were diagnosed with non-CLL mature B-cell variants. Strong, uniform surface co-expression of CD200 and CD160 was detected in 94.7% (36 of 38) of the chronic lymphocytic leukemia cases. In contrast, splenic marginal zone lymphoma cohorts demonstrated a complete absence of CD160 expression alongside dim or negative CD200 profiles (P < 0.001). Hairy cell leukemia variants exhibited bright CD200 paired with negative CD160 parameters. High expression density for both markers correlated with early clinical presentation (Binet Stage A). Incorporating CD200 and CD160 into standard immunophenotyping protocols provides excellent diagnostic specificity, reducing borderline scores and helping classify mature B-cell expansions.

Keywords: Chronic lymphocytic leukemia, CD200, CD160, flow cytometry, lymphoproliferative disorders, immunophenotyping

Manuscript Timeline: Received: October 14, 2018; Revised: November 25, 2018; Accepted: December 10, 2018; Published: January 16, 2019

International Journal of Hematology | Vol. 10, No. 7, July 2019 | pp. 49–56
DOI: 10.46882/2019/IJH/000115

Original Article

Title: Screening for lupus anticoagulant utilizing an integrated dRVVT and dilute Russell's venom confirmation index loop in patients with unprovoked venous thromboembolism

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 multiloop screening parameters to avoid false-positive diagnoses caused by circulating coagulation factor variations. This prospective diagnostic study evaluated the performance of an integrated dilute Russell’s viper venom time (dRVVT) screening, mixing, and high-phospholipid confirmation index protocol in 76 adult patients presenting with unprovoked lower limb deep vein thrombosis. Patient matrices underwent sequential 1:1 mixing steps paired with high-density bilayer phospholipid corrections to yield normalized target ratios. Lupus anticoagulant presence was confirmed in 21.0% (16 of 76) of the thromboembolic cohort. The integrated triple-loop confirmation protocol achieved a diagnostic sensitivity of 93.7% and a specificity of 91.6% when validated against international reference reference standard guidelines. Calculated confirmation ratios correlated positively with a clinical history of recurrent pulmonary embolism (r = 0.48, P < 0.05). Utilizing this multi-step electronic index loop minimizes the impact of baseline clotting factor deficiencies, providing a highly reliable and reproducible thrombophilia risk-profiling asset for specialized clinical pathology laboratories.

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

Manuscript Timeline: Received: April 14, 2019; Revised: May 20, 2019; Accepted: June 08, 2019; Published: July 16, 2019