Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

Muhury, Manas; Mathai, Alka Mary; Rai, Sharada; Naik, Ramadas; Pai, Muktha R; Sinha, Ruchi

doi:10.4103/0377-4929.56132

Cited by 23 publications

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“…This may be explained by the fact that WT mice had a small increase in ROS production post-TBI, which potentially hindered thrombopoiesis, though at yet compensated and undetectable levels. Additionally, in our previous study a significant increase in the number of megakaryocytes within BM compartment in IEX-1 KO mice post-TBI was shown [4], presumably as a compensatory mechanism for thrombocytopenia frequently seen in MDS and other diseases [22]. This increase in the number of megakaryocytes was almost completely normalized by MitoQ treatment, as suggested by a similar number of CD41 + megakaryocytes in both irradiated WT and KO mice post-MitoQ, in sharp contrast to significant differences in the mice prior to MitoQ treatment (Figure 3B).…”

Section: Resultsmentioning

confidence: 99%

Mitoquinone restores platelet production in irradiation-induced thrombocytopenia

Ramsey

Zhang

2014

Platelets

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Myelodysplastic syndromes (MDS) are hallmarked by cytopenia and dysplasia of hematopoietic cells, often accompanied by mitochondrial dysfunction and increases of reactive oxygen species (ROS) within affected cells. However, it is not known whether the increase in ROS production is an instigator or a byproduct of the disease. The present investigation shows that mice lacking immediate early responsive gene X-1 (IEX-1) exhibit lineage specific increases in ROS production and abnormal cytology upon radiation in blood cell types commonly identified in MDS. These affected cell lineages chiefly have the bone marrow as a primary site of differentiation and maturation, while cells with extramedullary differentiation and maturation like B- and T-cells remain unaffected. Increased ROS production is likely to contribute significantly to irradiation-induced thrombocytopenia in the absence of IEX-1 as demonstrated by effective reversal of the disorder after mitoquinone (MitoQ) treatment, a mitochondria-specific antioxidant. MitoQ reduced intracellular ROS production within megakaryocytes and platelets. It also normalized mitochondrial membrane potential and superoxide production in platelets in irradiated, IEX-1 deficient mice. The lineage-specific effects of mitochondrial ROS may help us understand the etiology of thrombocytopenia in association with MDS in a subgroup of the patients.

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Section: Resultsmentioning

confidence: 99%

Mitoquinone restores platelet production in irradiation-induced thrombocytopenia

Ramsey

Zhang

2014

Platelets

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“…[7–912] The mechanism behind this phenomenon is not completely understood. Some studies have shown that interactions between megakaryocytes and their environment, mediated by various cytokines and growth factors, are pivotal for the formation of dysplastic megakaryocytes.…”

Section: Discussionmentioning

confidence: 99%

Dysmegakaryocytopoiesis and maintaining platelet count in patients with plasma cell neoplasm

2013

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Background:Dysmegakaryocytopoiesis in patients with the plasma cell neoplasm (PCN) is rarely discussed in the literature. The puzzling phenomenon, which PCN patients maintaining normal platelet count even when the marrow is mostly replaced by plasma cells, is hardly explored.Aim:This study was aimed to determine the frequency of dysmegakaryocytopoiesis in PCN and the relationships between bone marrow (BM) plasma cell percentage, plasma cell immunomarkers, the severity of dysmegakaryocytopoiesis, and peripheral blood platelet count in PCN.Materials and Methods:We randomly selected 16 cases of PCN, among which 4 were with monoclonal gammopathy of undetermined significance and 12 were with plasma cell myeloma.Results:Our study showed that: (1) Dysmegakaryocytopoiesis was present in all the selected cases of PCN and its severity was not correlated with the percentage of the plasma cells in BM; (2) almost all patients maintained normal platelet count even when BM was mostly replaced by plasma cells; (3) immunomarkers of the neoplastic plasma cells were not associated with dysmegakaryocytopoiesis or maintaining of platelet count. The possible mechanisms behind dysmegakaryocytopoiesis and maintaining of platelet count were also discussed.Conclusion:Despite the universal presence of dysmegakaryocytopoiesis in PCN, the platelet count is maintained at normal range.

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“…A defect in any of the stages of megakaryocytopoiesis can lead to dysmegakaryocytopoiesis and thrombocytopenia. 2 Thrombocytopenia is defined as platelet count less than 1,50,000/mm 3 . It is the most common cause of abnormal bleeding.…”

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confidence: 99%

“…However, they are also observed in megakaryocytes in non-myelodysplastic hematological conditions like immune thrombocytopenic purpura (ITP), infection associated thrombocytopenia (IAT), hypersplenism, aplastic anaemia (AA), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), leukemia lymphoma syndrome (LLS), bone marrow metastasis, blast crisis of chronic myeloid leukemia; but scant data exist on the prevalence of dysplastic changes in megakaryocytes in non-myelodysplastic hematological conditions. 2 A study done in 1995 showed that MDS is characterized by the presence of atypical micromegakaryocytes. 4 Increase in number of megakaryocytes with immature forms were seen in Idiopathic Thrombocytopenic Purpura ( ITP) in 2009.…”

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confidence: 99%

“…4 Increase in number of megakaryocytes with immature forms were seen in Idiopathic Thrombocytopenic Purpura ( ITP) in 2009. 2 In 2010, a study showed megakaryocytes to be hyperlobated with fine stippled chromatin in megaloblastic anaemia. 5 Similarly, a study done in 2012 concluded that immunemediated thrombocytopenic purpura (ITP) is characterized by significant morphologic alterations in megakaryocytes in the bone marrow.…”

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confidence: 99%

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Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

Pokharel

Upadhyaya²,

Karki³

et al. 2016

J Pathol Nep

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Background: Megakaryocyte morphology plays an important role in thrombopoiesis. A defect in any stage of megakaryocytopoiesis can lead to dysmegakaryocytopoiesis and thrombocytopenia. This study was conducted to understand megakaryocytic alterations and their contribution in the diagnosis of cases of thrombocytopenia.Materials and Methods: This was a cross-sectional study was conducted on all consecutive cases of bone marrow aspirates of thrombocytopenia over a duration of one year in BPKIHS. Megakaryocyte morphology was studied with a 100X objective. Data were entered into Microsoft excel 10 and analysed with SPSS version 11.5. Descriptive statistics charted and Chi-square tests were done for inferential statistics to find any association at 95% Confidence Interval.Results: Among the 38 subjects, megakaryocytic thrombocytopenia (44.7%) was the most common cause of thrombocytopenia. Hypolobated megakaryocytes (63.2%), bare megakaryocytic nuclei (57.9%) were the common morphological changes in megakaryocytes. Odds of increased megakaryocyte count in megakaryocytic thrombocytopenia was found to be 12.5 times than for other causes of thrombocytopenia and the presence of bare megakaryocytic nuclei in MTP was statistically significant. (p –value<0.05)Conclusion: Many similarities were observed in megakaryocytic morphology among different hematological diseases. However, increased megakaryocyte count and presence of bare megakaryocytic nuclei, hypolobated forms were significant in megakaryocytic thrombocytopenia.

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Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

Abstract: Careful understanding of the morphological changes of megakaryocytes in bone marrow aspirates can improve the diagnostic accuracy for a wide range of hematological disorders thereby enabling proper therapeutic interventions.

Cited by 23 publications

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Mitoquinone restores platelet production in irradiation-induced thrombocytopenia

Mitoquinone restores platelet production in irradiation-induced thrombocytopenia

Dysmegakaryocytopoiesis and maintaining platelet count in patients with plasma cell neoplasm

Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

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