Peripheral Blood Smear Atypical Lymphocytes Association With Covid-19 Mortality

@#Introduction: COVID-19 disease is currently pandemic, and its prevalence in Saudi Arabia is concerning. The SARSCoV-2 virus primarily affects the lungs, but it also affects the haematopoietic system. The atypical lymphocytes on peripheral blood film that have a distinct morphological appearance were of particular interest in this study. Our goal was to see a link between atypical lymphocytes and COVID-19 patient mortality. Methods: This four-month single-centered prospective descriptive study was conducted in Makkah, Saudi Arabia. COVID-19 patients of both genders were randomly selected based on inclusion criteria. The data from the patient’s electronic medical record was extracted. All patients’ peripheral blood film parameters were recorded on days 3, 7, and 14 after admission. The statistical data was analysed using SPSS version 23. The Fisher’s exact test was used to determine the relationship with mortality. A p value of 0.05 was considered significant. Results: The total number of cases enrolled in the study was 226. The patients’ average age was 58 years (SD 0.5289). On the third day of admission, 88.2 % of patients with COVID-19 had atypical lymphocytes, with a mean of 2.35 ± 0.927. A significant correlation (p < 0.001) exists between atypical lymphocytes decreasing percentage number on the 3rd, 7th, and 14th days of admission and death. Conclusion: The decrease in the number of atypical lymphocytes on peripheral blood film has a significant association with the patients’ mortality. This fact can be used to develop a tailored management strategy based on the observation of peripheral blood film.

Linfocitose extrema associada à leucemia linfoblástica aguda (LLA) de células T em um cão jovem: relato de caso / Extreme lymphocytosis associated with acute T-cell lymphoblastic leukemia(ALL) in a young dog: case report

A leucemia linfoblástica aguda (LLA) é uma enfermidade de origem linfóide e consiste na proliferação de células neoplásicas na medula óssea. O objetivo desse trabalho é relatar o caso de um cão macho, sem raça definida, de apenas um ano de idade, atendido no Hospital Universitário de Medicina Veterinária Prof. Firmino Mársico Filho (HUVET) da Universidade Federal Fluminense (UFF) com queixa principal de inapetência e diarreia há três dias e que foi diagnosticado com essa neoplasia por meio da sintomatologia clínica, resultados do hemograma e do mielograma. O paciente apresentava valores exacerbados de linfócitos (553.094 células/µL), além de anemia, trombocitopenia, hipoalbuminemia e elevação da atividade das enzimas fosfatase alcalina e ALT. Foram observadas manchas de Gümprecht, linfócitos atípicos apresentando anisocitose, anisocariose, intensa basofilia citoplasmática e monócitos ativados. O mielograma apresentou também um aumento de linfócitos e contagem de linfoblastos superior a 30% na medula, confirmando o diagnóstico de leucemia linfoblástica aguda. Ademais, posteriormente, foi realizado exame de Reação em Cadeia de Polimerase (PCR) para rearranjos de receptores de antígenos e foi detectado clonalidade para linfócitos T. O animal foi submetido à quimioterapia (protocolo com ciclofosfamida, vincristina e prednisona), mas não resistiu à gravidade do quadro, vindo a óbito após a primeira sessão, pouco tempo após o diagnóstico.

Acute lymphoblastic leukemia (LLA) is a disease with a lymphoid origin and consists of the proliferation of neoplastic cells in the bone marrow. The aim of this study was to report the case of only one year old mixed breed male dog, attended at the University Hospital of Veterinary Medicine Prof. Firmino Mársico Filho (HUVET) from Universidade Federal Fluminense (UFF), with major complaint of inappetence and diarrhea three days ago and which was diagnosed with this neoplasm through clinical symptoms, complete blood count and myelogram results. The patient had increased values of lymphocytes (553,094 cells/μL), in addition to anemia, thrombocytopenia, hypoalbuminemia and elevated alkaline phosphatase and ALT activities. Gümprecht shadows, atypical lymphocytes presenting anisocytosis, anisocariosis, and severe cytoplasmic basophilia and activated monocytes were observed. Myelogram also showed an increase in lymphocytes and a lymphoblastic count greater than 30% in the marrow, confirming the diagnosis of LLA. In addition, polymerase chain reaction (PCR) for antigen receptor rearrangements was performed and clonality for T lymphocytes was detected. The animal underwent chemotherapy (protocol with cyclophosphamide, vincristine and prednisone), but did not withstand the severity of the disease, coming to death after the first session, shortly after diagnosis.

Linfocitose extrema associada à leucemia linfoblástica aguda (LLA) de células T em um cão jovem: relato de caso / Extreme lymphocytosis associated with acute T-cell lymphoblastic leukemia (ALL) in a young dog: case report

A leucemia linfoblástica aguda (LLA) é uma enfermidade de origem linfóide e consiste na proliferação de células neoplásicas na medula óssea. O objetivo desse trabalho é relatar o caso de um cão macho, sem raça definida, de apenas um ano de idade, atendido no Hospital Universitário de Medicina Veterinária Prof. Firmino Mársico Filho (HUVET) da Universidade Federal Fluminense (UFF) com queixa principal de inapetência e diarreia há três dias e que foi diagnosticado com essa neoplasia por meio da sintomatologia clínica, resultados do hemograma e do mielograma. O paciente apresentava valores exacerbados de linfócitos (553.094 células/µL), além de anemia, trombocitopenia, hipoalbuminemia e elevação da atividade das enzimas fosfatase alcalina e ALT. Foram observadas manchas de Gümprecht, linfócitos atípicos apresentando anisocitose, anisocariose, intensa basofilia citoplasmática e monócitos ativados. O mielograma apresentou também um aumento de linfócitos e contagem de linfoblastos superior a 30% na medula, confirmando o diagnóstico de leucemia linfoblástica aguda. Ademais, posteriormente, foi realizado exame de Reação em Cadeia de Polimerase (PCR) para rearranjos de receptores de antígenos e foi detectado clonalidade para linfócitos T. O animal foi submetido à quimioterapia (protocolo com ciclofosfamida, vincristina e prednisona) mas não resistiu à gravidade do quadro, vindo a óbito após a primeira sessão, pouco tempo após o diagnóstico.

Acute lymphoblastic leukemia (LLA) is a disease with a lymphoid origin and consists of the proliferation of neoplastic cells in the bone marrow. The aim of this study was to report the case of only one year old mixed breed male dog, attended at the University Hospital of Veterinary Medicine Prof. Firmino Mársico Filho (HUVET) from Universidade Federal Fluminense (UFF), with major complaint of inappetence and diarrhea three days ago and which was diagnosed with this neoplasm through clinical symptoms, complete blood count and myelogram results. The patient had increased values of lymphocytes (553,094 cells/µL), in addition to anemia, thrombocytopenia, hypoalbuminemia and elevated alkaline phosphatase and ALT activities. Gümprecht shadows, atypical lymphocytes presenting anisocytosis, anisocariosis, and severe cytoplasmic basophilia and activated monocytes were observed. Myelogram also showed an increase in lymphocytes and a lymphoblastic count greater than 30% in the marrow, confirming the diagnosis of LLA. In addition, polymerase chain reaction (PCR) for antigen receptor rearrangements was performed and clonality for T lymphocytes was detected. The animal underwent chemotherapy (protocol with cyclophosphamide, vincristine and prednisone), but did not withstand the severity of the disease, coming to death after the first session, shorly after diagnosis.

Significance of lymphocyte structure parameters of Sysmex XN-9000 hematology analyzer in screening peripheral atypical lymphocytes / 第二军医大学学报

[Abstract] Objective To investigate the significance of lymphocyte structure parameters of Sysmex XN-9000 hematology analyzer in screening peripheral blood atypical lymphocytes when positive alarm of atypical lymphocytes occurs. Methods From Dec. 2017 to Dec. 2018, 370 blood samples with positive alarm of atypical lymphocytes, which were detected by XN-9000 hematology analyzer in outpatient and emergency department of Changhai Hospital, Naval Medical University (Second Military Medical University), were collected in this study. Six lymphocyte structure parameters were recorded, including lymphocyte complexity (L-X), lymphocyte fluorescence intensity (L-Y), lymphocyte size (L-Z), dispersion width of lymphocyte complexity (L-WX), dispersion width of lymphocyte fluorescence intensity (L-WY) and dispersion width of lymphocyte size (L-WZ). According to the atypical lymphocyte proportion detected manually under microscope, the 370 samples were divided into 2 groups: atypical lymphocyte positive group (100 samples with an atypical lymphocyte proportion5%) and atypical lymphocyte negative group (270 samples with an atypical lymphocyte proportion≤5%), and the significance of each lymphocyte structure parameter was evaluated by receiver operating characteristic (ROC) curve. Then the parameters with high accuracy for screening atypical lymphocytes were analyzed by logistic regression model to study the significance of their combination. Results The lymphocyte structure parameters L-WY, L-X and L-Z had high accuracies in screening atypical lymphocytes, with the ROC area under curve (AUC) being 0.927, 0.939 and 0.931, respectively. The combined predictor was generated using L-WY, L-X and L-Z by logistic regression analysis model, and the ROC AUC of combined predictor was 0.979. When 0.058 1 was selected as the cut-off value, the sensitivity was 100.0% and the specificity was 77.8%. Conclusion Lymphocyte structure parameters L-WY, L-X and L-Z detected by Sysmex XN-9000 hematology analyzer can effectively screen peripheral blood atypical lymphocytes when positive alarm of atypical lymphocytes occurs.

Clinicopathological profile of peripheral blood lymphocytosis

Background: Reactive lymphocytes can be presented with a different number of morphologies. The significance of evaluation of lymphocytes on peripheral smear tests and its clinical correlation are still neglected. Materials and methods: Clinical details along with other clinical investigations like cell counter results of patients presented with lymphocytosis and other hematological parameters including hemoglobin, total WBC count and platelet count, were collected from Department of Pathology, Dhanalakshmi Srinvasan Medical College and Hospital, India. Results: A total number of 120 cases were studied, out of which 82 patients showed absolute lymphocyte count more than 4000/ul. Out of the 120 patients, a total of 31 patients had history of smoking/tobacco chewing. 18(58%) of them showed reactive/ atypical lymphocyte morphology and 13(41%) of them showed mature lymphocytes. Of the 10 patients with alcoholism history, only 4 of them showed a normal morphology of lymphocytes, other 6 patients showed reactive lymphocyte morphology. Only one patient in the study population showed atypical lymphocytes and in peripheral smear and subjected to lymph node biopsy and rest of the patient failed to follow up after advised biopsy. Conclusions: Current study also reports that, lymphocytosis with reactive lymphocytes have a correlation with acute stress, smoking, and other ailments.

Dynamics of differential count in dengue

Background: Dengue can occur as epidemics in India. Early diagnosis reduces mortality. Differential white cell count can aid in diagnosing and prognosticating Dengue in resource limited areas. Aim and objectives of this study were to assess patterns and utility of Differential counts in Dengue.Methods: A total of 132 serologically positive Dengue cases were analysed over the month of November 2016. Hematology data obtained from analysers and Leishman smears were tabulated and analysed.Results: The study showed lymphocytosis as the predominant pattern (65%) followed by neutropenia (30%), neutrophilia (11%), eosinophilia (5%), monocytosis (5%) and basophilia (4%). Atypical lymphocytosis ? 15% were noted in 65% of the cases with 83% showing Plasmacytoid lymphocytes, 8% apoptotic lymphocytes and 43% showed other atypical lymphocytes. Also, 52% of lymphocytosis and 33% of neutrophilia cases showed severe thrombocytopenia (? 0.5 lakhs per cu mm). Lymphocytosis was noted to be an early event but was established in later stages as seen with serology pattern association, 28% associated with NS1 antigen test (non-structural protein 1) and 42% with antibody pattern. However, neutrophilia with 60% of cases seen in antibody pattern was a late event. Plasmacytoid lymphocytosis was noted uniformly through all serology patterns in contrast with other atypical lymphocytosis which was seen mostly (48%) in antibody pattern. Apoptotic lymphocytosis was also a late event associated mainly with antibody pattern (55%).Conclusions: The Differential white cell count can be a useful supplementary test along with serology in resource limited peripheral areas. It additionally serves to drastically reduce morbidity and mortality.

Sulfasalazine Induced DRESS Syndrome: A Review of Case Reports.

Introduction: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is designated as a lethal adverse drug effect with characteristic sign and symptoms such as skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytes, lymph node enlargement, and liver or renal dysfunction. Incidences of the DRESS range from 1/1000-1/10,000 drug exposures and are associated with a mortality rate of 10%. Pathogenesis of DRESS relates to an abnormal immune response in a genetically vulnerable individual, i.e. presence of human leukocyte antigen (HLA)*5801 and HLA-B* 5701 genotype and slow acetylation metabolic pathways. Methods: 48 cases were associated with the “Sulfasalazine-induced DRESS syndrome” reported between January 1990- March 2015 in PubMed-MEDLINE and HighWire Press. The “RegiSCAR” scoring system was used to analyze the case reports. Using this system, cases were classified into 4 categories as “no”, “possible, “probable” and “definite”. Results: The vast majority of cases were classified as “probable/definite” DRESS cases (83%). Hypereosinophilia, atypical lymphocytes and fever were significantly associated with “probable/ definite” DRESS cases. Liver involvement and skin rash was described in almost all of the cases, including “possible cases”. DRESS was found fatal in two cases. Conclusion: Awareness of DRESS is essential for diagnosis with the presence of skin rash, liver involvement, fever, hyper eosinophilia and lymphadenopathy. Early identification, followed by a prompt withdrawal of the culprit drug is the most essential measure to avoid disease evolution and to restore wellness.

Análise da integração viral e clonalidade de linfócitos T na dermatite infecciosa associada ao HTLV-1 / Analysis of viral integration and T lymphocyte clonality in infective dermatitis associated with HTLV-1

A dermatite infecciosa associada ao vírus linfotrópico de células T humanas tipo 1 (HTLV-1), DIH, é uma forma de eczema grave e recidivante que incide principalmente em crianças que em geral foram verticalmente infectadas pelo HTLV-1, ocorrendo lesões eritematosas, escamativas e crostosas, sendo geralmente localizadas nas regiões do couro cabeludo e retroauriculares, assim como pescoço, virilha, região paranasal, axilas, ouvido externo e narinas. Inicia-se após os 18 meses de vida e raramente persiste até a vida adulta. No Brasil, muitos casos têm sido diagnosticados na Bahia, estado brasileiro que atualmente conta com a maior casuística da literatura depois da Jamaica. Acompanhando uma coorte de 31 pacientes da faixa etária infanto-juvenil com DIH em Salvador, observou-se em esfregaço do sangue periférico, em 11 dos indivíduos, o aparecimento de linfócitos atípicos (LA) e/ou células em flor (CF), que não são comumente observados em pacientes com DIH, mas ocorrem com frequência em pacientes com leucemia/linfoma de células T do adulto (ATL). Submetemos amostras dos 31 pacientes a reações em cadeia da polimerase (PCR)...

Infective dermatitis associated with human T lymphotropic cells virus type 1 (HTLV-1), IDH, is a form of severe and recurrent dermatitis that occurs mostly in children who were mainly vertically infected with HTLV-1, occurring erythematous, desquamative and crusty, being generally located in regions of the scalp and retroauricular, neck, groin, paranasal region, armpits, outer ear and nostrils. It begins after 18 months of life and rarely persists into adulthood. In Brazil, several cases have been diagnosed in Bahia, the Brazilian state that currently has the highest incidence after Jamaica. Tracking a cohort of 31 patients in the juvenile age group with IDH in Salvador, we observed the appearance of atypical lymphocytes (AL) and/or flower cells (FC), which are not commonly observed in patients with IDH, but occur frequently in patients with adult T cell leukemia/lymphoma (ATL), in peripheral blood smear in 11 of the subjects. Samples of 31 patients underwent tests of PCR...

Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil / Linfócitos atípicos na leptospirose: coorte de pacientes hospitalizados entre 1996 e 2009, Estado do Rio de Janeiro

INTRODUCTION: Leptospirosis is a zoonotic disease found in tropical and temperate countries, and its clinical diagnostic confusion with arboviruses (dengue fever, oropouche fever and yellow fever), Brazilian spotted fever, viral hepatitis and hantaviruses has been an ongoing public health concern. The aim of this observational study was to demonstrate an association between findings of atypical lymphocytosis and the progression of endemic leptospirosis. METHODS: A retrospective analysis was performed on the demographic, epidemiological, clinical and laboratory aspects of 27 human leptospirosis cases that occurred over a period of 13 years (1996-2009) with no reported epidemic outbreaks in Rio de Janeiro, Brazil. RESULTS: The overall mortality rate was 11.1 percent in our cohort of hospitalized cases. However, there was no mortality among patients with atypical lymphocytosis (OR = 11.1; 95 percent CI = 1.12-110.9; p = 0.04). Two patients who were in the septicemic phase showed signs of expansion of γδ T cell responses in peripheral blood. CONCLUSIONS: Atypical lymphocytosis may be observed in patients with leptospirosis. Our observations suggest that these atypical leukocyte subsets are associated with partial protection during the disease course of leptospirosis.

INTRODUÇÃO: Leptospirose é uma zoonose que permanece endêmica em regiões tropicais e temperadas. A dificuldade no diagnóstico clínico diferencial entre os quadros de leptospirose humana e as várias arboviroses (dengue, febre amarela, febre de oropouche), febre maculosa brasileira, hepatite viral e hantavirose permanece um problema na Saúde Pública. MÉTODOS: No presente estudo, foi realizada análise retrospectiva de características demográficas, epidemiológicas, clínicas e laboratoriais de 27 casos de leptospirose humana que ocorrerem durante um período de 13 anos sem ocorrência de notificação de surtos epidêmicos no Rio de Janeiro, Brasil (1996-2009). RESULTADOS: A mortalidade da coorte de pacientes com leptospirose correspondeu a 11,1 por cento, sem embargo, o grupo de pacientes com atipia linfocitária não evoluiu para o óbito (OR = 11,1; 95 por cento CI = 1,12-110,9; p = 0.04). Em duas oportunidades, foi observada uma expansão dos linfócitos T gama-delta no sangue periférico de pacientes na fase septicêmica da leptospirose. CONCLUSÕES: Atipia linfocitária pode ocorrer em pacientes com leptospirose. Nossos dados também sugerem que os linfócitos atípicos podem estar envolvidos na patogênese da leptospirose.

Postchemotherapy Changes in Cytokine Levels and Their Correlation with Hematological Parameters in Patients with Vivax Malaria / 임상검사와정도관리

BACKGROUND: Inflammatory cytokines play an important role in human immune responses to malaria, although the role of these mediators in pathogenesis is unclear. In this study, we evaluated changes in cytokine levels following chemotherapy, and determined whether cytokine levels in serum correlated with the hematological parameters in the Korean vivax malarial patients. METHODS: The study population was composed of 31 patients in Inje University Ilsan Paik Hospital who were diagnosed with Plasmodium vivax infection. Cytokine profiles, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels, were assessed in serum samples obtained from the malaria patients three times, at the time of diagnosis (stage I) and after treatment with hydroxychloroquine (stage II) and primaquine (stage III). The level of each cytokine was measured using commercially available serum-based ELISA kits. Hematological parameters were simultaneously measured using a hematology autoanalyzer. RESULTS: At thetime of diagnosis, the TNF-alpha (mean, 62.9 pg/mL), IL-6 (mean, 45.5 pg/mL), and IL-10 (mean, 237.7 pg/mL) levels in the malaria patients were higher than the reference values. After treatment with hydroxychloroquine, these levels (TNF-alpha, P<0.01; IL-6, P<0.05; IL-10, P<0.01) significantly decreased to near-normal levels. Significant positive correlations were observed among the cytokine levels, but not between the cytokine levels and other hematological parameters. CONCLUSIONS: In this study, TNF-alpha, IL-6, and IL-10 levels increased at the time of diagnosis and rapidly decreased to normal levels after treatment the levels of these cytokines did not correlate with other hematological parameters.

Acute Retroviral Syndrome Presenting as Infectious Mononucleosis / General Medicine

ABSTRACT: A case of infectious mononucleosis (IM) in a previously healthy 43-year-old male is presented. The patient complained of fever and a sore throat of 3 weeks' duration. Although blood tests showed a marked increase in atypical lymphocytes, tests for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative. Human immunodeficiency virus type 1 (HIV-1) antibody was positive on enzymelinked immunosorbent assay (ELISA), and the HIV-1 viral load was 6.4×10<SUP>4</SUP>copies/mL. Western blot (WB) analysis did not initially confirm HIV-1 infection ; however, HIV-1 infection was confirmed one month after presentation. Although several pathogens can cause infections presenting as IM, in Japan there have been few reports of acute retroviral syndrome presenting as IM. This case is being reported to stress the importance of the early diagnosis of acute retroviral syndrome.

Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase / 华中科技大学学报（医学）（英德文版）

In order to explore the value of combined detection of atypical lymphocytes (ATL) and transaminase (alanine aminotransferase, ALT; asparate aminotransferase, AST) in the diagnosis of infectious mononucleosis (IM), The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis (AH) patients, 44 upper respiratory infection (URI) patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously (ALT＞40 IU/L,AST＞45 IU/L) in 57.4% (31/54) IM patients. There was significant difference (P＜0.01) between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

A Case of Lupus Erythematosus Panniculitis with Infiltration of Atypical Lymphocytes / 대한피부과학회지

Lupus erythematosus panniculitis is a rare variant of lupus erythematosus primarily involving a panniculus with or without discoid lupus erythematosus in the overlying skin. A 34-year-old woman showed multiple, variable-sized, indurated subcutaneous nodules on both her upper arms and axillae. A Histopathological examination revealed lobular panniculitis with infiltration of several hyperchromatic atypical large lymphocytes. The infiltrated cells were positively stained with LCA, UCHL-1, CD4, CD8, but not with CD20 and CD68. A T cell receptor -chain gene and immunoglobulin heavy chain gene rearrangement study showed no monoclonality. The result of an ANA test was positive at 1: 40 in a homogeneous pattern. Skin lesions were improved by combined therapy with daily hydroxychloroquine 400mg and prednisolone 10mg in a week and after 6weeks, resolved with atrophic depressed scars. After 4 months, she complained of symptoms of the Raynaud phenomenon and was managed by nifedipine. There has been no recurrence during follow-up for 7 months.