scholarly journals Acute leukemia in sickle cell disease patients in a tertiary health facility in Nigeria: a case series

2020 ◽  
Vol 20 (3) ◽  
pp. 1304-1312 ◽  
Author(s):  
Oladapo W Aworanti ◽  
Foluke A Fasola ◽  
Taiwo R Kotila ◽  
John A Olaniyi ◽  
Biobele J Brown
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Acute Leukaemia ◽  
Film Review ◽  
Case Series ◽  
Blood Film ◽  
Cell Disease ◽  
Peripheral Blood Film

Background and objectives: Sickle cell disease(SCD) is a disorder of red cells resulting from the co-inheritance of hae- moglobin S (HbS) with another abnormal haemoglobin. The diagnosis of acute leukaemia is uncommon in our patients with sickle cell disease more so the patients have high morbidity and mortality due to the sickling process.Acute leukemia is a malignant clonal disorder of haemopoietic precursor cells resulting in accumulation of immature blood cells in the bone marrow and blood.The objective of the case series was to highlight the challenges of diagnosis and management of SCD patients with acute leukaemia, the importance of peripheral blood film review and propound a possible risk factor. Methods: Records of 58 patients diagnosed and managed for acute leukaemia over a 7 year period at the University College Hospital, Ibadan were reviewed. The diagnosis of acute leukaemia was based on clinical features in addition to peripheral and bone marrow smears findings. Microsoft excel version 2013 was used for statistical analysis. Results: Five (8.6%) of the patients with acute leukaemia also had sickle cell disease: 3 males and 2 females were described. Recurrent fever and anaemia were the most consistent presenting features in the patients. All the patients were not on any routine medications meant for SCD patients and had poor history of clinic attendance prior to the diagnosis of acute leu- kaemia. The diagnosis of acute leukaemia was not made until the patients were seen by a haematologist. The principal tool of diagnosis in all the patients was peripheral blood film review. Two patients were discharged against medical advice.The treatment period ranged between one month and one year in the remaining three patients. Conclusion: SCD patients are not exempted from developing acute leukaemias and the diagnoses of the two conditions overwhelms the social and economic support of patients and care givers.The study also underscores the relevance of high level of suspicion and prompt review of peripheral blood film of SCD patients particularly when patients present with un- remitting symptoms associated with anaemia and fever. Keywords: Acute leukaemia; sickle cell disease; anaemia.

scholarly journals Correlation of HbF, HbA2, and HbS in sickle cell disease and its prevalence in Nigerian patients: A case series of 2 patients

2021 ◽  
pp. 324-326
Author(s):  
Garima Agarwal ◽  
Shefali Goyal ◽  
Natasha Singh ◽  
Gaurav Garg ◽  
Jyoti Mishra
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Case Series ◽  
Blood Film ◽  
West African ◽  
Cell Disease ◽  
African Countries ◽  
Red Cell Indices ◽  
Nigerian Population ◽  
Red Blood Cell Indices

Sickle cell disease (SCD) is the most common inherited disorder of hemoglobin worldwide. In Nigeria, the prevalence of SCD is 20–30/1000 live births. The burden of the disease has reached a level where it contributes 9–16% of the under-five mortality in many West African countries. This case series evaluated the chromatographic patterns and red blood cell indices of sickle cell homozygous patients. Red cell indices, blood film, sickle solubility test, and chromatographic patterns using Bio-Rad HPLC D10 were evaluated for both patients. Both the patients were Nigerian and HPLC showed HbS window 81.7 and 81.6% and increased HbF, that is, 7.5 and 8.8%. HbA2 was normal in both the cases, that is, 2.2 and 2.6%. Our data suggest that homozygous sickle cell disease is very common among the Nigerian population with an increase in HbF along with HbS and HbA2 is normal.

Altered Hematopoiesis in Murine Sickle Cell Disease

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1451-1459 ◽  
Author(s):  
Marie-José Blouin ◽  
Monique E. De Paepe ◽  
Marie Trudel
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Compensatory Mechanism ◽  
Allogeneic Bone ◽  
Cell Disease ◽  
Multipotent Cells ◽  
Colony Forming Units

Abstract We investigated the mechanisms of sickle cell disease (SCD) hematopoietic/erythropoietic defects using bone marrow, spleen, and/or peripheral blood from the transgenic SAD mouse model, which closely reproduces the biochemical and physiological disorders observed in human SCD. First, the erythropoietic lineage late precursors (polychromatophilic normoblasts to the intramedullary reticulocytes) of SAD mouse bone marrow were significantly altered morphologically. These anomalies resulted from high levels of hemoglobin polymers and were associated with increased cell fragmentation occurring during medullary endothelial migration of reticulocytes. Secondly, analysis of bone marrow erythropoiesis in earlier stages showed a marked depletion in SAD erythroid burst-forming units (BFU-E; of ∼42%) and erythroid colony-forming units (CFU-E; of ∼23%) progenitors, despite a significant increase in their proliferation, suggesting a compensatory mechanism. In contrast to the bone marrow progenitor depletion, we observed (1) a high mobilization/relocation of BFU-E early progenitors (∼4-fold increase) in peripheral blood of SAD mice as well as of colony-forming units–granulocyte-macrophage (CFU-GM) and (2) a 7-fold increase of SAD CFU-E in the spleen. Third, and most importantly, SAD bone marrow multipotent cells (spleen colony-forming units [CFU-S], granulocyte-erythroid-macrophage-megakaryocyte colony-forming units [CFU-GEMM], and Sca+Lin−) were highly mobilized to the peripheral blood (∼4-fold increase), suggesting that peripheral multipotent cells could serve as proliferative and autologous vehicles for gene therapy. Therefore, we conclude the following. (1) The abnormal differentiation and morphology of late nucleated erythroid precursors result in an ineffective sickle erythropoiesis and likely contribute to the pathophysiology of sickle cell disorders; this suggests that transfer of normal or modified SCD bone marrow cells may have a selective advantage in vivo. (2) A hematopoietic compensatory mechanism exists in SAD/SCD pathology and consists of mobilization of multipotent cells from the bone marrow to the peripheral blood and their subsequent uptake into the spleen, an extramedullary hematopoietic site for immediate differentiation. Altogether, these results corroborate the strong potential effectiveness of both autologous and allogeneic bone marrow transplantation for SCD hematopoietic therapy.

Altered Hematopoiesis in Murine Sickle Cell Disease

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1451-1459
Author(s):  
Marie-José Blouin ◽  
Monique E. De Paepe ◽  
Marie Trudel
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Compensatory Mechanism ◽  
Allogeneic Bone ◽  
Cell Disease ◽  
Multipotent Cells ◽  
Colony Forming Units

We investigated the mechanisms of sickle cell disease (SCD) hematopoietic/erythropoietic defects using bone marrow, spleen, and/or peripheral blood from the transgenic SAD mouse model, which closely reproduces the biochemical and physiological disorders observed in human SCD. First, the erythropoietic lineage late precursors (polychromatophilic normoblasts to the intramedullary reticulocytes) of SAD mouse bone marrow were significantly altered morphologically. These anomalies resulted from high levels of hemoglobin polymers and were associated with increased cell fragmentation occurring during medullary endothelial migration of reticulocytes. Secondly, analysis of bone marrow erythropoiesis in earlier stages showed a marked depletion in SAD erythroid burst-forming units (BFU-E; of ∼42%) and erythroid colony-forming units (CFU-E; of ∼23%) progenitors, despite a significant increase in their proliferation, suggesting a compensatory mechanism. In contrast to the bone marrow progenitor depletion, we observed (1) a high mobilization/relocation of BFU-E early progenitors (∼4-fold increase) in peripheral blood of SAD mice as well as of colony-forming units–granulocyte-macrophage (CFU-GM) and (2) a 7-fold increase of SAD CFU-E in the spleen. Third, and most importantly, SAD bone marrow multipotent cells (spleen colony-forming units [CFU-S], granulocyte-erythroid-macrophage-megakaryocyte colony-forming units [CFU-GEMM], and Sca+Lin−) were highly mobilized to the peripheral blood (∼4-fold increase), suggesting that peripheral multipotent cells could serve as proliferative and autologous vehicles for gene therapy. Therefore, we conclude the following. (1) The abnormal differentiation and morphology of late nucleated erythroid precursors result in an ineffective sickle erythropoiesis and likely contribute to the pathophysiology of sickle cell disorders; this suggests that transfer of normal or modified SCD bone marrow cells may have a selective advantage in vivo. (2) A hematopoietic compensatory mechanism exists in SAD/SCD pathology and consists of mobilization of multipotent cells from the bone marrow to the peripheral blood and their subsequent uptake into the spleen, an extramedullary hematopoietic site for immediate differentiation. Altogether, these results corroborate the strong potential effectiveness of both autologous and allogeneic bone marrow transplantation for SCD hematopoietic therapy.

Sickled Erythrocyte Morphology in the Bone Marrow of Patients with Sickle Cell Disease: Previously Unrecognized Forms of Sickled Erythrocytes May Have a Pathogenetic Role in Bone Pain of Painful Crises.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3802-3802
Author(s):  
George T. Roberts
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Morphological Characteristics ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Erythrocyte Morphology ◽  
Pathogenetic Role ◽  
Hbf Level

Abstract Background: The painful crises of sickle cell disease (SCD) are characteristically localized to the skeleton. Various lines of evidence suggest that bone and bone marrow (BM) infarction contribute to the pathophysiology of such pain in which sickled red blood cells (SRBC) are believed to play a part. However, there is little information about the morphological characteristics and role of SRBC in BM during the crises or indeed, in the “steady state”. Occasional light microscopic observations in the BM of SCD patients show numerous markedly distorted cells, presumed to be SRBC, types of which have not been previously reported from this site or the peripheral blood (PB). We therefore studied a series of BM biopsies from SCD patients to determine whether such changes are consistently present. Methods: We microscopically reviewed archival BM biopsies from SCD patients for abnormally shaped RBC and compared the findings with SRBC on Wright-stained smears of PB collected simultaneously with the biopsies. The material consisted of Wright-Giemsa stained smears of aspirated BM and hematoxylin-eosin stained histological sections of clotted aspirate and / or trephine biopsies. We also examined fresh BM RBC by scanning and transmission electron microscopy (EM). We determined the relationship between the percentage of SRBC in BM and PB on the one hand, and fetal hemoglobin (HbF) levels on the other. Results: We studied the BM of 43 SCD patients. By LM, we observed markedly distorted RBC in the BM of the majority of patients who also had BM SRBC that were more typical forms. The distorted forms included vastly elongated erythrocytes, measuring up to 40 microns in length and less than 1 micron in width, some fixed into rod like structures, but others as sinuous, snake-like forms that have not been previously described. Scanning EM appearances also confirmed the features observed by LM. By contrast, none of PB samples showed similarly distorted SRBC. Although the percentage of typical SRBC in BM was concordant with that in the PB (p<0.001) SRBC numbers in both PB and BM were inversely proportional to the level of HbF.(Table 1) Conclusion: We conclude that the proportions of markedly distorted SRBC present in the BM of SCD patients are inversely proportional to HbF level and may thus play a pathogenetic role in the localization of severe pain to the skeleton during painful crises. Table 1. Correlations between sickled RBC estimates and blood fetal hemoglobin levels MSRBC MARROW MBMSRBC MSRBCLOT+TREPHINE MSRBC PB MSRBC= Mean SRBC marrow and peripheral blood together. MBMSRBC = Mean SRBC in bone marrow aspirates only. MSRBCLOT+TREPHINE = Mean SRBC, clotted marrow aspirate and trephine together. MSRBCPB = Mean SRBC in peripheral blood. MHbF = Mean HbF level in blood. r = correlation coefficient. NS = Not significant. MHbF MHbF MHbF MHbF r −0.3806 −0.3293 −0.2685 −0.384 p < 0.05 < 0.05 NS < 0.05

Chimerism and cure: hematologic and pathologic correction of murine sickle cell disease

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4582-4593 ◽  
Author(s):  
Leslie S. Kean ◽  
Elizabeth A. Manci ◽  
Jennifer Perry ◽  
Can Balkan ◽  
Shana Coley ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Mixed Chimerism ◽  
Cell Disease ◽  
Complete Replacement ◽  
Curative Therapy ◽  
Number Of Patients

AbstractBone marrow transplantation (BMT) is the only curative therapy for sickle cell disease (SCD). However, the morbidity and mortality related to pretransplantation myeloablative chemotherapy often outweighs the morbidity of SCD itself, thus severely limiting the number of patients eligible for transplantation. Although nonmyeloablative transplantation is expected to reduce the risk of BMT, it will likely result in mixed-chimerism rather than complete replacement with donor stem cells. Clinical application of nonmyeloablative transplantation thus requires knowledge of the effect of mixed chimerism on SCD pathophysiology. We have, therefore, created a panel of transplanted SCD mice that received transplants displaying an array of red blood cell (RBC) and white blood cell (WBC) chimerism. A significant enrichment of RBC over WBC chimerism occurred in these mice, because of the dramatic survival advantage of donor over sickle RBCs in the peripheral blood. Increasing levels of RBC chimerism provided progressive correction of hematologic and pathologic abnormalities. However, sickle bone marrow and splenic hematopoiesis was not corrected until peripheral blood sickle RBCs were fully replaced with donor RBCs. These results have important and unexpected implications for nonmyeloablative BMT for SCD. As the critical hematopoietic organs were not corrected without full RBC replacement, 100% peripheral blood RBC chimerism becomes the most important benchmark for cure after nonmyeloablative BMT. (Blood. 2003;102:4582-4593)

scholarly journals The Effect of Sodium Cyanate on Globin Synthesis

Blood ◽  
1973 ◽  
Vol 41 (5) ◽  
pp. 635-639 ◽  
Author(s):  
Michael Habib ◽  
Veronica Watson ◽  
Elias Schwartz
Keyword(s):  
Bone Marrow ◽  
Protein Synthesis ◽  
Sickle Cell Disease ◽  
Total Synthesis ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Cell Disease ◽  
Hemoglobin Synthesis ◽  
Globin Synthesis ◽  
Sodium Cyanate

Abstract The incubation of peripheral blood with sodium cyanate produced dose-related suppression of hemoglobin synthesis. Addition of 5 mM sodium cyanate reduced globin synthesis in the peripheral blood of a patient with sickle cell disease by 34%, while 25 mM cyanate reduced synthesis by 92%. The relative synthesis of α- and β-chains remained constant despite the reduction of total synthesis. The effects were also found in peripheral blood and bone marrow of patients without hemoglobinopathies. The results suggest that further studies of the effect of cyanate on protein synthesis are necessary before widespread use of the drug in sickle cell disease.

scholarly journals Evidence for complement-mediated bone marrow necrosis in a young adult with sickle cell disease

2021 ◽  
Vol 86 ◽  
pp. 102508
Author(s):  
Melissa Azul ◽  
Surbhi Shah ◽  
Sarah Williams ◽  
Gregory M. Vercellotti ◽  
Alexander A. Boucher
Keyword(s):  
Bone Marrow ◽  
Young Adult ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Bone Marrow Necrosis
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