International Journal of Hematology

International Journal of Hematology | Vol. 14, No. 10, October 2023 | pp. 73–80
DOI: 10.46882/2023/IJH/000164

Original Article

Title: Impact of systemic hydroxyurea on plasma soluble thrombomodulin levels and microvascular velocity tracking in adult 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: Continuous endothelial cell desquamation and low nitric oxide states fuel widespread microvascular shearing and high pulmonary pressures in sickle cell anemia. This prospective cohort study evaluated the long-term impact of optimized hydroxyurea therapy on plasma soluble thrombomodulin (sTM) levels, an index of direct endothelial injury, and tricuspid regurgitant jet velocity (TRJV) shifts in 50 adult patients presenting with steady-state sickle cell anemia (HbSS). Hydroxyurea was administered at maximum tolerated doses (15 to 25 mg/kg/day) and monitored over 12 months. Plasma markers were quantified via an enzyme-linked immunosorbent assay, and velocities were tracked using Doppler echocardiography. Baseline mean soluble thrombomodulin levels fell significantly from 14.2 ± 3.8 ng/ml to 6.2 ± 1.1 ng/ml at month 12 (P < 0.001). Concurrently, the proportion of patients presenting with high-risk velocity metrics (TRJV ≥ 2.5 m/s) fell from 36.0% to 14.0%. Thrombomodulin suppression correlated strongly with an increase in fetal hemoglobin from 5.2% to 15.6% and a drop in serum lactate dehydrogenase. These findings confirm that hydroxyurea successfully preserves endothelial integrity, limiting vascular damage and progressive cardiopulmonary remodeling in adult sickle cell variants.

Keywords: Sickle cell anemia, hydroxyurea, thrombomodulin, endothelial injury, tricuspid regurgitant jet velocity

Manuscript Timeline: Received: July 12, 2023; Revised: August 20, 2023; Accepted: September 10, 2023; Published: October 14, 2023

International Journal of Hematology | Vol. 14, No. 4, April 2023 | pp. 25–32
DOI: 10.46882/2023/IJH/000158

Original Article

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

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 classic hemolytic uremic syndrome variants. Evaluations were conducted on 125 adult patients presenting with thrombocytopenia and microcytosis, and diagnoses were validated via serum ferritin, Shiga-toxin screening, and manual visual blood film schistocyte counts. Classic hemolytic uremic syndrome was confirmed in 50 cases, while 75 presented with severe iron deficiency anemia. The mean immature reticulocyte fraction was significantly higher in the hemolytic uremic syndrome 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: January 15, 2023; Revised: February 22, 2023; Accepted: March 14, 2023; Published: April 19, 2023

International Journal of Hematology | Vol. 14, No. 1, January 2023 | pp. 1–8
DOI: 10.46882/2023/IJH/000155

Original Article

Title: Screening for lupus anticoagulant using a simplified textrin time and thromboplastin time mixing protocol in 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: Diagnosing antiphospholipid syndrome requires robust laboratory testing parameters that can successfully isolate circulating inhibitors from baseline clotting factor variations. This prospective diagnostic study evaluated the performance of a combined screening protocol using the textrin time (TT) and the standard activated partial thromboplastin time (aPTT) mix loop to detect lupus anticoagulant in 70 adult patients presenting with unprovoked lower limb venous thrombosis. Patient matrices underwent sequential 1:1 mixing steps with normal pooled plasma, 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 textrin-aPTT mixing protocol achieved a diagnostic sensitivity of 92.8% and a specificity of 90.1% when cross-validated against international guidelines. Mixing indexes correlated positively with a history of recurrent thrombotic episodes (r = 0.48, P < 0.05). Notably, the textrin step resisted interference from low-molecular-weight heparin due to its specific prothrombin-activating mechanism, providing a highly reliable and cost-effective screening asset for regional laboratories handling patients on active anticoagulation.

Keywords: Lupus anticoagulant, textrin time, activated partial thromboplastin time, mixing studies, venous thromboembolism

Manuscript Timeline: Received: October 14, 2022; Revised: November 20, 2022; Accepted: December 08, 2022; Published: January 14, 2023

International Journal of Hematology | Vol. 14, No. 3, March 2023 | pp. 17–24
DOI: 10.46882/2023/IJH/000157

Case Report

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

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 VIII 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 isolated, severe prolongation of activated partial thromboplastin time (88.4 seconds) with a normal prothrombin time. A 1:1 mixing study with normal pooled plasma failed to correct the activated partial thromboplastin time, indicating a specific intrinsic pathway inhibitor. Functional assays confirmed severely depressed Factor VIII activity (< 1.0%), and a Bethesda assay quantified a Factor VIII 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 high-dose corticosteroids was unsuccessful. However, a targeted rituximab protocol (375 mg/m² weekly for 4 weeks) successfully cleared the inhibitor (0 BU) and normalized Factor VIII activity by week 8. This case demonstrates that acquired Factor VIII autoantibodies require immediate diagnostic differentiation and multi-modal therapeutic strategies.

Keywords: Acquired factor VIII inhibitor, retroperitoneal hemorrhage, intrinsic pathway, bypassing agents, rituximab

Manuscript Timeline: Received: December 14, 2022; Revised: January 20, 2023; Accepted: February 12, 2023; Published: March 18, 2023

International Journal of Hematology | Vol. 13, No. 1, January 2022 | pp. 1–8
DOI: 10.46882/2022/IJH/000143

Review Article

Title: Structural architecture and target chemical inhibition of the TP53 pathways in therapy-related acute myeloid leukemia

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: Mutations within the tumor suppressor TP53 gene occur frequently in therapy-related acute myeloid leukemia, correlating with complex karyotypes and severe resistance to standard DNA-damaging cytotoxic chemotherapies. This comprehensive review synthesizes the molecular structural architecture of TP53 disruptions, contrasting missense alterations within the DNA-binding domain with complete multi-allelic deletions. These structural modifications impair p53-mediated transcriptional activation of pro-apoptotic elements, allowing highly abnormal myeloid clones to survive and multiply. Traditional anthracycline and cytarabine induction regimens fail to achieve durable remission in over 80% of TP53-mutated cases. Evolving treatment frameworks emphasize small-molecule targeted therapies, including eprenetapopt (APR-246), which acts by restoring standard wild-type confirmation to mutated p53 proteins, and selective MDM2 inhibitors for TP53 wild-type overexpressing variants. Combining these confirmation restoration agents with low-intensity hypomethylating backbones represents a promising frontier for bypassing standard chemoresistance. This review outlines a clear molecular risk assessment checklist, variant allele fraction tracking systems, and clinical management pathways designed to optimize clonal clearance in therapy-related leukemias.

Keywords: Acute myeloid leukemia, TP53 mutation, eprenetapopt, chemoresistance, tumor suppressor pathways

Manuscript Timeline: Received: October 12, 2021; Revised: November 22, 2021; Accepted: December 10, 2021; Published: January 16, 2022

International Journal of Hematology | Vol. 13, No. 5, May 2022 | pp. 33–40
DOI: 10.46882/2022/IJH/000147

Case Report

Title: Spontaneous massive retroperitoneal hemorrhage secondary to acquired Factor X inhibitor development in an elderly patient: Successful resolution with azathioprine

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 X 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 severe 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 specific common pathway inhibitor. Functional assays confirmed severely depressed Factor X activity (< 1.5%), and a Bethesda assay quantified a Factor X inhibitor titer of 22.0 Bethesda Units. Hemostasis was achieved using prothrombin complex concentrates alongside supportive measures. Subsequent immunosuppressive therapy with oral prednisone paired with azathioprine (100 mg daily) cleared the inhibitor (0 BU) and normalized Factor X activity by week 8. This case demonstrates that acquired common pathway autoantibodies require immediate diagnostic differentiation and multi-modal therapeutic strategies.

Keywords: Acquired factor X inhibitor, retroperitoneal hemorrhage, common pathway, prothrombin complex concentrate, azathioprine

Manuscript Timeline: Received: February 15, 2022; Revised: March 24, 2022; Accepted: April 11, 2022; Published: May 19, 2022