bone marrow examination
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2022 ◽  
Vol 12 ◽  
Author(s):  
Ramon Diez-Feijóo ◽  
Juan Jose Rodríguez-Sevilla ◽  
Concepcion Fernández-Rodríguez ◽  
Solange Flores ◽  
Carmen Raya ◽  
...  

Late onset neutropenia (LON) related to rituximab or rituximab plus chemotherapy is defined as an unexplained absolute neutrophil count of ≤1.5 × 109/L starting at least four weeks after the last rituximab administration. LON is infrequent and its pathophysiology remains unknown. There are no guidelines or consensus strategies for the optimal management of patients developing LON. The majority of the patients recover promptly with no specific treatment and only some cases need to be managed with granulocytic colony stimulating factor (G-CSF), usually with a rapid response. Here, we describe a 69-year-old patient with Waldenström’s macroglobulinemia who presented a septic event in the context of severe LON after rituximab plus bendamustine. The diagnosed of agranulocytosis was established by bone marrow examination. Interestingly, anti-neutrophil antibodies bound to the patient’s granulocytes were found suggesting an autoimmune mechanism. The patient did not respond to G-CSF but achieved a rapid response after high doses of intravenous immunoglobulins with full white blood cell recovery.


Author(s):  
Upendra Mahat ◽  
Bhavuk Garg ◽  
Chao-Yie Yang ◽  
Hrishikesh Mehta ◽  
Rabi Hanna ◽  
...  

Neutrophils migrate into inflamed tissue, engage in phagocytosis, and clear pathogens or apoptotic cells. These processes require well-coordinated events involving the actin cytoskeleton. We describe a child with severe neutropenia and episodes of soft tissue infections and pneumonia. Bone marrow examination showed granulocytic hypoplasia with dysplasia. Whole exome sequencing revealed a de novo heterozygous missense mutation in LCP1, which encodes the F-actin binding protein Lymphocyte Cytosolic Protein 1. To determine its pathophysiologic significance, we stably transduced cells with a doxycycline-inducible wild type LCP1 and LCP1 I232F lentiviral constructs. We observed dysplastic granulocytic 32D cells expressing LCP1 I232F cells. These cells showed decreased proliferation without a block in differentiation. Additionally, expression of LCP1 I232F resulted in a cell cycle arrest at G2/M phase, but it did not lead to increased levels of genes involved in apoptosis or the unfolded protein response. Both 32D and HeLa cells expressing mutant LCP1 showed impaired cell motility and invasiveness. Flow cytometry showed increased F-actin. However, mutant LCP1-expressing 32D cells demonstrated normal oxidative burst upon stimulation. Confocal imaging and subcellular fractionation revealed diffuse intracellular localization of LCP1, but only the mutant form was found in the nucleus. We conclude that LCP1 is a new gene involved in granulopoiesis, and the missense variant LCP1 I232F leads to neutropenia and granulocytic dysplasia with aberrant actin dynamics. Our work supports a model of neutropenia due to aberrant actin regulation.


2021 ◽  
Vol 71 (6) ◽  
pp. 1920-24
Author(s):  
Tayyaba Ashiq ◽  
Ammara Hafeez ◽  
Abdus Sattar ◽  
Nasiruddin . ◽  
Naureen Saeed ◽  
...  

Objective: To determine the diagnostic accuracy of serum ferritin and soluble serum transferrin receptor (sTfR), taking bone marrow iron stain as a gold standard for iron deficiency anaemia in heterogeneous group of patients. Study Design: Cross-sectional diagnostic accuracy study. Place and Duration of Study: Department of Diagnostic, Combined Military Hospital Lahore, from Mar to Aug 2020. Methodology: A total of 55 adult patients, of both genders, undergoing bone marrow examination for any reason were enrolled. Patients with known hemolytic condition (sickle cell anemia, megaloblastic anemia), taking erythropoietin/iron supplements, transfused red cell concentrate (RCC) recently or undergoing chemotherapy were excluded. Age, gender, clinical history and results of bone marrow examination, complete blood count (CBC), serum Ferritin and C-reactive protein (CRP) were recorded. Results: Serum ferritin was found to be less sensitive (28%) but more specific (100%) for reflecting reduced bone marrow iron stores as compared to sTfR (sensitivity: 60%, specificity: 96.6%). sTfR had highest likelihood ratio (15) and diagnostic accuracy (80%). On Receiver Operator Characteristic (ROC) graph Transferrin index (AUC=0.908) showed maximum accuracy, followed by Ferritin (AUC=0.884) and sTfR (AUC=0.879). Conclusion: Serum soluble transferring receptor (sTfR) and transferrin index has advantage over serum ferritin alone in predicting the bone marrow iron stores and differentiating iron deficiency anemia from anemia of chronic disease.


Author(s):  
Sneha Roy ◽  
Sourav Nath ◽  
Rashmi Rekha Goswami ◽  
S. A. Sheikh

Background: Leukemia, the malignant proliferation of hematopoietic cells, accounts for a major portion of cancer globally. Types of leukemia are necessary for effective therapy as prognosis, and survival rates are different for each type of leukemia. The objective of the study was to know the relative incidence of leukemia in Silchar Medical College and Hospital, Assam. This study also aims to know the clinical manifestations of leukemia and their hematological correlation.Methods: It was a retrospective study of 60 patients carried out in the Department of Pathology in SMCH, Assam, over a period of 2 years from April 2019 to March 2021. Diagnosis was based on peripheral blood count, peripheral blood smear and bone marrow examination for morphology, along with cytochemistry study whenever required.Results: In this study, acute leukemia was more prevalent than chronic leukemia. The most common form was CML followed by AML, ALL and then CLL. Male predominance was observed in this study with male: female ratio = 1.7:1. Conclusions: In our study, Acute leukemia was more prevalent than chronic leukemia. Leukemia affected male more than female. In this study, the frequency of AML is more than that of ALL but number of cases of CML exceeds that of AML.


Author(s):  
Ponvijaya Yadav ◽  
Vijayashree S. Gokhale ◽  
Rupesh Parati ◽  
Keyuri Mehta

Immune thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without any apparent cause. Some patients may be diagnosed during routine blood investigations or may present with bleeding diathesis. Treatment required for moderate to severe thrombocytopenia or those with bleeding manifestations. We present a case of 43 year old male, sputum positive pulmonary tuberculosis on isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) with persistent thrombocytopenia. He developed hepatitis hence isoniazid (INH) and rifampicin were stopped. He had fever, rash, purpura, hematuria and blood tinged sputum with platelet count of 10,000. 4 random donor platelets (RDPs) given. He suffered from mild COVID-19 infection and recovered in 2 weeks but platelets remained low. Bone marrow examination was suggestive of ITP. Inspite of steroid therapy no improvement was seen. Later was treated with injection romiplostim, and started on systemic lupus erythematosus (SLE) regimen for tuberculosis and discharged with regular follow up. Last platelet count being 1,20000/dl, liver function tests normal and now restarted on HRZE.


2021 ◽  
pp. 1-6
Author(s):  
Eveline Vancraeynest ◽  
Marleen Renard ◽  
Thomas Tousseyn ◽  
Christophe M. Deroose ◽  
Anne Uyttebroeck ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1017-1017
Author(s):  
Karthika K V ◽  
Mobin Paul ◽  
Anjana K V ◽  
Ullas Mony ◽  
Ganeshprasad Arunkumar ◽  
...  

Abstract BACKGROUND Next Generation Sequencing (NGS) has been enormously rewarding in the field of diagnostic hematology. In particular, the diagnosis of inherited disorders has progressed in leaps and bounds. These patients tend to remain undiagnosed for a long period of time not only because of unavailability of molecular diagnostics but also due to lack of cognizance and atypical presentations. Thrombocytopenia (TCP) is a common hematological presentation and can lead to chronic hospital visits to life-threatening bleeds. Most of these patients have acquired disorders such as immune TCP, malignancies, liver disease etc. However, some of them are likely to have unidentified inherited causes. We thus intended to study the utility of NGS in the definitive diagnosis of unexplained TCPs with or without other cytopenias to understand the clinicopathologic characteristics of these patients. METHODOLOGY This was a retrospective descriptive study done at two centres over three years from May 2018 to May 2021. Patients with TCP with one of the following: (a) positive family history (b) clinical/ laboratory clues to an inherited cause (c) chronic TCP with no response to conventional therapies and sent for clinical exome sequencing done by NGS were included in the study. Patients who were negative for germline mutations were excluded. Sequencing of targeted genes was performed on the Illumina platform with a mean coverage of >80-100X. Mutations annotated as pathogenic, likely pathogenic and variant of uncertain significance (VUS) were considered clinically significant. VUS are mutations that are difficult to classify as pathogenic and require clinical validation and family testing. RESULTS Our cohort included 18 patients and were divided into two groups- cases of isolated TCP and cases of TCP with anemia and/or neutropenia. Patients presenting with isolated thrombocytopenia We had nine cases of isolated TCP out of which there were three cases of X-linked macrothrombocytopenia with MYH9 mutation, two cases of Wiskott Aldrich syndrome (WAS) and one case each of congenital thrombotic thrombocytopenic purpura (TTP), atypical Hemolytic Uremic Syndrome (HUS), Fanconi anemia (FA) and grey platelet syndrome. The demographic and mutational characteristics are described in Table 1. Clinical and laboratory clues were present in 7 cases, such as chronic kidney disease, micro/ macrothrombocytopenia, neutrophil inclusions etc. Bone marrow examination was carried out in 4 cases- the significant dyspoiesis in FA and myelofibrosis in grey platelet syndrome mislead to a diagnosis of MDS and myelofibrosis respectively. Seven patients had received treatment with steroids, immunosuppressants, splenectomy, danazol and TPO mimetics before the NGS diagnosis. Patients presenting with thrombocytopenia and other cytopenias This group consisted of nine cases with two cases each of Dyskeratosis Congenita (DKC) and WAS and one case each of TTP, Ghosal hematodiaphyseal dysplasia, Congenital Amegakaryocytic Thrombocytopenia (CAMT), B-cell immunodeficiency with hypogammaglobulinemia type-25 and double homozygous for FA and DKC. The majority of patients in this group were young and had lower platelet counts (Table 2). The most common associated cytopenia was anemia. Phenotypic clues to diagnosis were present in cases of DKC and WAS. The common differentials considered in this group were inherited bone marrow failure syndromes (IBMFS), congenital immunodeficiency syndromes etc. Bone marrow examination was done more frequently in these patients and showed hypocellular marrow in IBMFS and absent megakaryocytes in CAMT. These patients have also been treated with steroids, IVIg, danazol and TPO mimetics. CONCLUSION Patients with inherited isolated TCPs have a chronic course and heterogenous causes therefore tend to be diagnosed later in life. However, patients with TCPs and other cytopenias tend to present at a younger age with infrequent family history. IBMFS was the most common disorder identified in this latter group of patients. Positive family history, clinical and laboratory clues and absence of response to conventional therapies should prompt workup of inherited causes by NGS to avoid long term ineffectual treatment. Further, NGS mutations, in particular VUS have to be interpreted with caution with the help of parental study, clinical presentation, in-silico analysis and inputs from molecular and genetic experts. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4623-4623
Author(s):  
Mohamed A Yassin ◽  
Sadek A Nehmeh ◽  
Abdulqadir Jeprel Nashwan ◽  
Samah Kohla ◽  
Shehab Fareed Mohamed ◽  
...  

Abstract Background Among several groups of clinicians and hematopathologists a conflict of opinion has been repeatedly expressed concerning the validity of bone marrow (BM) features characterizing myeloproliferative neoplasms (MPNs). In this regard, controversy is mainly focused on the distinction between essential thrombocythemia (ET) and pre-fibrotic/early primary myelofibrosis (pre-PMF) Although other groups confirmed the characteristic BM features and emphasized the clinical impact to discriminate both MPN subtypes the existence of pre-PMF has been questioned, including clinical usefulness and particularly reproducibility of the corresponding diagnostic guidelines. In this context, it has been criticized that the MPN classification proposed by the World Health Organization (WHO), updated in 2008 and revised in 2016,was focused on BM morphology as the gold standard of diagnosis. The current standard for follow-up of these patients is based on pathological markers (peripheral blood counts and/ bone marrow histomorphology) and molecular markers. Bone marrow examination is the gold standard method to assess the disease's extent; it offers detailed information about cellularity, the morphology of each lineage, the degree of fibrosis, and the transformation and dysplastic features. However, many patients are reluctant to go for this invasive technique which precludes precise disease activity assessment at the desirable frequencies. A non-invasive technique that can offer reliable prognostic and predictive information about the disease is lacking. The objective of this study is to explore the diagnostic value of FLT-PET in malignant hematopoiesis of Pre-PMF and ET. The potential to use FLT-PET metrics to differentiate between Pre-PMF and ET is assessed Methods A total of 13 patients (mean age of 43.23 ± 14.42 years, 7 males and 6 females) with Essential Thrombocythemia (ET) and/or Prefibrotic myelofibrosis were included in this study. One male subject was excluded due to an inconclusive diagnosis. The study was approved by the institutional review board. Written informed consents were obtained from all subjects. Each subject underwent FLT PET imaging as well as bone marrow examination (gold standard) and all were tested for JAK2v617F , CALR and MPL . Semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen and Lumbar spine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <0.05 is considered to be statistically significant. Discussion: Pre-PMF and ET exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. And in another scenario, bone marrow which is mandated for diagnosis, cannot be obtained due to technical issues or patient-related factors. In the 2016 revised classification,pre-PMF was recognized as a separate entity, distinct from ET. Thrombosis and hemorrhage represent two of the main causes of morbidity and mortality in patients with ET. Incidence of arterial and venous thrombosis prior to diagnosis revealed no significant differences (23% /20 and 9/8%) in WHO-defined ET compared with pre-PMF; thrombotic complications were also similar during the follow-thrombosis is not significantly different, whereas bleeding is more frequent in pre-PMF.From clinical prespective it is important to differentiate between the two categories. Results The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P>0.05). In contrast, TLG measurements in the LSpine were statistically different (P=0.013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion TLG of the Lumbar Spine in FLT PET images is a potential quantitative parameter to discriminate between ET and PRE-PMF patients Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Saniya Sharma ◽  
Ravinder Kaur Sachdeva ◽  
Man Updesh Singh Sachdeva ◽  
Sreejesh Sreedharanunni ◽  
Shano Naseem ◽  
...  

2021 ◽  
Vol 10 (40) ◽  
pp. 3533-3537
Author(s):  
Arvind Chouhan ◽  
Fuzail Ahmad ◽  
Manisha Jain

BACKGROUND This is a clinic-haematological study, conducted in Sidhanta Hospital, Bhopal, to identify the causes of pancytopenia. Out of total 1200 cases of complete hemograms, 56 cases were categorized as pancytopenias, and out of these, 24 cases were subjected to bone marrow examination. The remaining 32 cases of pancytopenia, were put on periodic follow up with peripheral blood smear examination, based on clinical data. Pancytopenia is the simultaneous presence of anaemia, leucopenia and thrombocytopenia that may result from various disease processes, involving the bone marrow primarily or secondarily. Pancytopenia is reduction in all the three cellular components of the blood, namely red blood cells (RBCs), leucocytes (WBCs) and platelets. It is a common entity which is encountered by practitioners. The presentation is in the form of cytopenias leading to infections, anaemia, or bleeding manifestations. All the cases of pancytopenia need a through approach to reach to the cause of the same so that it can be managed in the best possible manner. Cytopenias are reduction in any of the three cellular components of the blood i.e. RBCs, WBCs or platelets. It can be reduction in two cellular components (bicytopenia) or a reduction in all the three cellular components (pancytopenia). In bicytopenia, the most common combination to be seen is anaemia and thrombocytopenia, whereas the least common is leucopenia with thrombocytopenia. (1) For practical purposes, it should have haemoglobin < 10 g%, absolute neutrophil count < 1,500/cumm and platelets < 1,00,000/cumm. It is labelled as severe when the three values are < 7 g%, < 500/cumm and < 20,000/cumm respectively. The purpose of this study was to find out different causes of pancytopenia and the use of bone marrow examination in evaluation of pancytopenia. METHODS This is a cross sectional study, conducted exclusively in the Department of Medicine, at a tertiary care hospital, in Bhopal from August 2019 to December 2019. A total of 56 cases of pancytopenia were analysed with clinico-haematological features. Criteria for diagnosis of pancytopenia were: Haemoglobin less than 10 gm/dl, TLC less than 4000/mm3 and platelet count less than 1,00,000/mm3. We have correlated the complete hemogram findings with bone marrow examination (if required) and peripheral smear examination in order to analyse the root cause of every case of pancytopenia. Pancytopenia is a haematological entity, we have to analyse the cause of it in order to find out the correct diagnosis and treat the patient accordingly. Bone marrow examination is useful in the investigation of PUO (pyrexia of unknown origin), as it leads to an etiological diagnosis in many of the cases. RESULTS In these 56 cases, only 24 cases (42.85 %) were subjected for bone marrow examination. Commonest cause of pancytopenia was episode of viral fever constituting 28 cases (50 %). CONCLUSIONS In cases of PUO, bone marrow examination is a very useful investigation. In cases diagnosed as idiopathic thrombocytopenic purpura (ITP), when the patient does not show improvement in counts, a repeat bone marrow examination should be done, as very rarely; acquired amegakaryocytic thrombocytopenia may be the cause. Though bone marrow examination is an absolute indication in cases of pancytopenia, it is important to wait for at least 2 – 3 weeks, and do a repeat hemogram, especially in cases of viral fever where the counts usually improve after fever subsides. KEY WORDS Pancytopenia, Bone Marrow, Viral Fever


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