RESUMO
Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature. To that end, a multi-vessel microfluidic device recapitulating the size-scale and geometry of the microvasculature was designed to investigate how Hct/Hgb interacts with acute leukemia to induce "in vitro" leukostasis. Using patient samples and cell lines, the degree of leukostasis was different among leukemia immunophenotypes with respect to white blood cell (WBC) count and Hct/Hgb. Among lymphoid immunophenotypes, severe anemia is protective against in vitro leukostasis and Hct/Hgb thresholds became apparent above which in vitro leukostasis significantly increased, to a greater extent with B-cell acute lymphoblastic leukemia (ALL) versus T-cell ALL. In vitro leukostasis in acute myeloid leukemia was primarily driven by WBC with little interaction with Hct/Hgb. This sets the stage for prospective clinical studies assessing how red cell transfusion may affect leukostasis risk in immunophenotypically different acute leukemia patients.
Assuntos
Viscosidade Sanguínea , Transfusão de Eritrócitos , Humanos , Microvasos , Leucostasia/etiologia , Hematócrito , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/sangue , Feminino , Masculino , Hemoglobinas/análiseRESUMO
Hyperleukocytosis in leukemic patients may cause tumour lysis syndrome, disseminated intravascular coagulopathy, and leukostasis, resulting in decreased tissue perfusion and increasing the risk of mortality. Since the myeloid blasts are larger than lymphoid blasts and are less deformable, complications of leukostasis are seen more frequently in myeloid leukemia. Priapism is a less common complication associated with leukostasis in leukaemia patients that should be treated as soon as possible to avoid ischemic injuries. Although chemotherapeutic drugs such as hydroxyurea and imatinib are used to treat hyperleukocytosis in CML patients, leukocytapheresis (LCP) can achieve rapid cytoreduction. Prophylactic LCP could not offer any advantage over aggressive chemotherapy, but therapeutic leukocyte depletion has a proven role in patients having symptomatic leukostasis due to high tumour burden. Three patients with ischaemic priapism were reported at our institute's emergency department, where detumescence could not be achieved by distal shunting or aspiration with phenylephrine instillation. The procedure of therapeutic LCP was performed in all three patients on an emergency basis, which resolved painful priapism by rapid cytoreduction.
Assuntos
Leucemia Mieloide , Leucostasia , Priapismo , Masculino , Humanos , Priapismo/terapia , Priapismo/complicações , Leucaférese/métodos , Leucostasia/terapia , Leucostasia/complicações , Centros de Atenção TerciáriaRESUMO
ABSTRACT: We show that red cell exchange (RCE) treats hyperleukocytosis in acute leukemia. RCE provided similar leukoreduction to standard therapeutic leukoreduction and could be superior in patients with severe anemia or monocytic leukemias or when requiring rapid treatment.
Assuntos
Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Leucostasia , Adulto , Humanos , Leucostasia/terapia , Leucemia Mieloide Aguda/terapia , Leucemia Monocítica Aguda/terapia , Doença Aguda , Leucaférese , Leucocitose/terapiaRESUMO
Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.
Assuntos
Encefalomielite Autoimune Experimental , Leucostasia , Esclerose Múltipla , Neurite Óptica , Camundongos , Animais , Tomografia de Coerência Óptica/métodos , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/patologia , Encefalomielite Autoimune Experimental/diagnóstico por imagem , Encefalomielite Autoimune Experimental/patologia , Inflamação/patologia , Modelos Animais de Doenças , AngiografiaRESUMO
Hyperleukocytosis, a white blood cell count greater than 100,000/mcl, can be associated with the following three primary oncologic emergencies: leukostasis, disseminated intravascular coagulation, and tumor lysis syndrome. Th.
Assuntos
Leucemia Mieloide Aguda , Leucostasia , Síndrome de Lise Tumoral , Humanos , Leucocitose/diagnóstico , Leucocitose/complicações , Pacientes Internados , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/terapia , LeucaféreseRESUMO
Acute myeloid leukemia is the most common acute leukemia in adults and up to 20% of patients present with hyperleukocytosis at the onset of the disease. The therapeutic approach involves medical support, cytoreductive treatment, and/or leukapheresis. Despite WBC count greater than 100.000/µL, not all patients develop symptoms. To clarify the role of leukapheresis in the setting of hyperleukocytotic AML, we aimed to find associations between AML morphologic subtypes and molecular alterations on presence or absence of leukostasis symptoms (and hence therapeutic vs prophylactic leukapheresis) and clinical outcomes in the cohort of 41 patients at our single center who underwent leukapheresis for hyperleukocytotic AML. There was a trend for increased WBC count, 30-day mortality, M4-M5 AML subtypes, and number of leukapheresis procedures performed in symptomatic hyperleukocytotic pts. No molecular marker was significantly associated with presence or absence of leukostasis symptoms due to small sample size, though there was a trend for increased NPM1-mutated and NPM1 + FLT3-mutated AML in asymptomatic patients and a greater proportion of symptomatic patients who were negative for all assessed molecular alterations. In conclusion, leukapheresis combined with cytoreductive treatment represents a synergic and efficient approach in the management of hyperleukocytosis especially in symptomatic patients considering the higher mortality independently from the presence of specific clonal markers whose distribution among the two groups may result more considerable with a higher number of patients.
Assuntos
Leucemia Mieloide Aguda , Leucostasia , Adulto , Humanos , Leucaférese , Leucostasia/terapia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Proteínas NuclearesRESUMO
Chronic lymphocytic leukemia (CLL) is a clonal mature B-cell neoplasm with a typically indolent clinical course. Though most clinicians follow these neoplasms through observation alone, an aggressive transformation to prolymphocytic leukemia, diffuse large-B-cell lymphoma (Richter transformation) or classical Hodgkin lymphoma requires immediate attention. We present a case of extreme leukocytosis (>1 million/µL) in a previously diagnosed CLL patient. Due to symptomatic leukostasis, she was started on cytoreductive therapies including leukocytapheresis. After three rounds of leukocytapheresis (LCP) and concurrent chemotherapy, her white blood cell count decreased from a maximum 1262 × 103 /µL to 574 × 103 /µL. To our knowledge, CLL with symptomatic leukostasis that required therapeutic LCP is rarely reported in literature. We propose that therapeutic LCP is of value in such rare, yet dangerous settings like our case.
Assuntos
Leucemia Linfocítica Crônica de Células B , Leucostasia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucaférese , Leucostasia/terapia , Contagem de Leucócitos , Leucocitose/terapiaRESUMO
Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1ß, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.
Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Leucostasia , Camundongos , Humanos , Animais , Retinopatia Diabética/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fator VIII/metabolismo , Fator VIII/farmacologia , Fator VIII/uso terapêutico , Células Endoteliais/metabolismo , Leucostasia/metabolismo , Retina/metabolismo , Proteínas Reguladoras de Apoptose/metabolismoRESUMO
BACKGROUND: In children with acute myeloid leukemia, the incidence of hyperleukocytosis is 5-33%. Patients with AML and hyperleukocytosis have a higher early mortality rate than patients with nonhyperleukocytic AML because of the increased risk of severe pulmonary and neurologic complications. Leukapheresis provides rapid cytoreduction and reduces early mortality rates. CASE PRESENTATION: In this report, we present a case with microcirculatory failure of upper extremities as a rare symptom of hyperleukocytic AML M4 at initial presentation. CONCLUSIONS: Early diagnosis and treatment of patients with AML admitted to emergency services with these symptoms is too important to prevent from loss of extremities. Most of the complications of hyperleukocytosis can be reversible with early treatment.
Assuntos
Leucemia Mieloide Aguda , Leucostasia , Criança , Humanos , Leucostasia/etiologia , Leucostasia/prevenção & controle , Microcirculação , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucaférese , Extremidade Superior , Leucocitose/terapiaRESUMO
BACKGROUND: For the past 30 years, white blood cell depletion (WBCD) or leukocytapheresis has been conducted to rapidly reduce excessive circulating white blood cell (WBC) concentrations in patients at risk for or with symptoms of leukostasis due to hyperleukocytosis. The goal of leukocytapheresis is to prevent or treat acute complications from leukostasis, thereby enabling patients to receive potentially curative chemotherapy. METHODS: This report details the results from a retrospective and a prospective clinical study conducted in the European Union and the People's Republic of China, which assessed the use of the Spectra Optia Apheresis System for leukocytapheresis in patients with hyperleukocytosis. The primary objective of both studies was to the assess the safety and performance of the WBCD procedure in patients with elevated WBC counts. RESULTS: Data were collected from 72 participants completing 87 WBCD procedures. The mean percent change in participant WBC counts post-procedure was 50.3 ± 21.2% and the collection efficiency (CE1) of the WBCD procedures was 53.7 ± 19.8%. Sixty-one participants (95.3%) experienced a total of 279 adverse events (AEs) with the majority of the AEs related to post-procedure changes in laboratory values, which is an anticipated AE in this patient population. CONCLUSION: The data collected within these studies indicate that the WBCD procedure is safe and well tolerated in patients with hyperleukocytosis as evaluated by percent decrease in WBC count, CE1, and AE incidence.
Assuntos
Leucostasia , Humanos , Leucostasia/terapia , Estudos Retrospectivos , Estudos Prospectivos , Leucócitos , Leucaférese/métodos , Contagem de LeucócitosRESUMO
Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.
Assuntos
Neoplasias Hematológicas , Leucostasia , Pneumopatias , Síndrome do Desconforto Respiratório , Neoplasias Hematológicas/complicações , Humanos , Infiltração Leucêmica/complicações , Infiltração Leucêmica/patologia , Leucostasia/complicações , Leucostasia/patologia , Pulmão/patologia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapiaRESUMO
Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-ß (Tgfß) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfß signaling in activated microglia during retinal NV. Using a tamoxifen-inducible, microglia-specific Tgfß receptor type 2 (Tgfßr2) knockout mouse [Tgfßr2 KO (ΔMG)] we show that Tgfß signaling in microglia actively represses leukostasis in retinal vessels. Furthermore, we show that Tgfß signaling represses expression of the pro-angiogenic factor, Insulin-like growth factor 1 (Igf1), independent of Vegf regulation. Using the mouse model of oxygen-induced retinopathy (OIR) we show that Tgfß signaling in activated microglia plays a role in hypoxia-induced NV where a loss in Tgfß signaling microglia exacerbates and prolongs retinal NV in OIR. Using human iPSC-derived microglia cells in an in vitro assay, we validate the role of Transforming Growth Factor-ß1 (Tgfß1) in regulating Igf1 expression in hypoxic conditions. Finally, we show that Tgfß signaling in microglia is essential for microglial homeostasis and that the disruption of Tgfß signaling in microglia exacerbates retinal NV in OIR by promoting leukostasis and Igf1 expression.
Assuntos
Leucostasia , Doenças Retinianas , Neovascularização Retiniana , Animais , Modelos Animais de Doenças , Hipóxia/complicações , Hipóxia/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Leucostasia/complicações , Leucostasia/metabolismo , Leucostasia/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Neovascularização Patológica/metabolismo , Oxigênio/metabolismo , Doenças Retinianas/metabolismo , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
Leukostasis is a life-threatening complication of high concentrations of circulating leukemic cells, most often myeloblasts. Effective care of patients with leukostasis involves early recognition and treatment, and aggressive management of concurrent complications of the underlying leukemia. The relatively poor prognosis in patients with leukostasis underscores the importance of the timely and effective care of this hematologic emergency. While cytoreductive measures such as hydroxyurea, corticosteroids, intravenous chemotherapy, and leukapheresis are available to urgently reduce high cell counts, characterization of the leukemia and initiation of tailored, definitive treatment is a parallel priority. However, data supporting any specific cytoreductive approach are limited, making clinical practice guided primarily by expert opinion. In this review, we discuss the pathophysiology, clinical manifestations, diagnosis, and management of leukemic hyperleukocytosis and leukostasis, with an emphasis on how to acutely manage this oncologic emergency in patients with acute myeloid leukemia, which is the most common cause of symptomatic leukostasis.
Assuntos
Leucemia Mieloide Aguda , Leucostasia , Doença Crônica , Humanos , Hidroxiureia/uso terapêutico , Leucaférese , Leucemia Mieloide Aguda/tratamento farmacológico , Leucocitose/diagnóstico , Leucocitose/etiologia , Leucocitose/terapia , Leucostasia/diagnóstico , Leucostasia/etiologia , Leucostasia/terapiaRESUMO
Leukapheresis (LA) in pediatric leukemia is performed for leukostasis, a life-threatening emergency in the setting of extremely increased blast cell counts. The authors aimed to assess the epidemiology of pediatric leukemia who received LA. The authors reviewed US nationally representative admission records of patients less than 20 years of age in the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, 2012, and 2016. Incidence of new leukemia cases who underwent LA were calculated for the years 2009, 2012, and 2016. Cox and logistic regression analyses were performed to ascertain the risk factors for adverse outcomes. There were 526 admissions for pediatric patients with acute lymphoblastic leukemia (ALL) (n=328), acute myeloid leukemia (AML) (n=124), or chronic myeloid leukemia (CML) (n=74) who underwent LA over the study period. The incidence of leukemia cases that required LA was lower in 2016 than in 2009 or 2012 (1.4%, 2.2%, and 2.7%, respectively; P=0.001). In-hospital mortality was higher in AML than ALL (hzard ratio, 3.2; 95% confidence interval, 1.1-9.1). None with CML died during admission. This first population-based study of LA in pediatric leukemia showed a decreased utilization of LA over recent years. The higher inpatient mortality in AML, as compared with ALL or CML, warrant further investigations.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda , Leucostasia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucaférese , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos RetrospectivosRESUMO
Purpose: CD40 is an upstream inducer of inflammation in the diabetic retina. CD40 is upregulated in retinal endothelial cells in diabetes. The purpose of this study was to determine whether expression of CD40 in endothelial cells is sufficient to promote inflammatory responses in the retina of diabetic mice. Methods: Transgenic mice with CD40 expression restricted to endothelial cells (Trg-CD40 EC), transgenic control mice (Trg-Ctr), B6, and CD40-/- mice were made diabetic using streptozotocin. Leukostasis was assessed using FITC-conjugated ConA. Pro-inflammatory molecule expression was examined by real-time PCR, immunohistochemistry, ELISA, or flow cytometry. Release of ATP was assessed by ATP bioluminescence. Results: Diabetic B6 and Trg-CD40 EC mice exhibited increased retinal mRNA levels of ICAM-1, higher ICAM-1 expression in endothelial cells, and increased leukostasis. These responses were not detected in diabetic mice that lacked CD40 (CD40-/- and Trg-Ctr). Diabetic B6 but not Trg-CD40 EC mice upregulated TNF-α, IL-1ß, and NOS2 mRNA levels. CD40 stimulation in retinal endothelial cells upregulated ICAM-1 but not TNF-α, IL-1ß, or NOS2. CD40 ligation did not trigger ATP release by retinal endothelial cells or pro-inflammatory cytokine production in bystander myeloid cells. In contrast to diabetic B6 mice, diabetic Trg-CD40 EC mice did not upregulate P2X7 mRNA levels in the retina. Conclusions: Endothelial cell CD40 promotes ICAM-1 upregulation and leukostasis. In contrast, endothelial cell CD40 does not lead to pro-inflammatory cytokine and NOS2 upregulation likely because it does not activate purinergic-mediated pro-inflammatory molecule expression by myeloid cells or induce expression of these pro-inflammatory molecules in endothelial cells.
Assuntos
Antígenos CD40/genética , Citocinas/genética , Retinopatia Diabética/genética , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular/genética , Óxido Nítrico Sintase Tipo II/genética , Receptores Purinérgicos P2X7/genética , Animais , Diabetes Mellitus Experimental/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Regulação da Expressão Gênica/fisiologia , Humanos , Leucostasia , Medições Luminescentes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Vasos Retinianos/citologia , Regulação para CimaRESUMO
Sudden death due to leukostasis and lymphocyte thrombi in patients with chronic hematologic malignancies is rare. Leukostasis is characterized by highly elevated leukemic cell count and decreased tissue perfusion symptoms, leading to severe complications and even death. Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder that shows a highly heterogeneous clinical course, ranging from indolent form to very aggressive disease. Due to its low metabolic and mitotic rate, there is a lower incidence of clinically significant leukostasis in patients with CLL. Two main theories have been proposed in the development of leukostasis: (1) increased blood viscosity due to large leukemic cell populations; (2) high metabolic activity and cytokine production by leukemic cells. Both mechanisms lead to local hypoxic damage.We present a case of a 70-year-old man who died suddenly in the absence of symptoms. Autopsy and histology examinations revealed findings consistent with CLL and diffuse leukostasis involving the major organs' vessels.In the presence of gross and/or microscopic findings suggesting a potential hematologic malignancy, undiagnosed or relapsing hematologic malignancies should be considered in the differential diagnosis of sudden deaths.
Assuntos
Leucemia Linfocítica Crônica de Células B , Leucostasia , Idoso , Morte Súbita/etiologia , Humanos , MasculinoRESUMO
Brown recluse spiders, also known as Loxosceles reclusa, are endemic to the Southwest and Central Midwestern United States. A bite from this spider can cause a range of clinical manifestations, anywhere from a painless papular lesion to life-threatening reactions. We report a possible spider bite presenting as leukostasis initially suspected to be acute leukemia. A 22-year-old female patient presented to the emergency department with confusion and right upper arm pain, redness, and swelling after a suspected spider bite. Initial labs showed WBC count of 103.5x10e3/µL, hemoglobin of 3.3 g/dL, positive Direct Coombs' test, creatinine of 1.8 mg/dL, transaminitis, and lactic acid of 20 mmol/L. Acute leukemia with leukostasis was suspected. She was started emergently on hydroxyurea in conjunction with prophylaxis for tumor lysis syndrome. However, peripheral smear showed left-shifted granulocytosis with lymphocytosis, monocytosis, and no blast cells or evidence of myelodysplasia. Bone marrow aspirate showed mildly hypercellular marrow with myeloid hyperplasia and no myelodysplasia. Flow cytometry analysis confirmed a left-shifted myeloid maturation pattern with 0.3% myeloblasts. BCR-ABL1 and JAK2 testing was negative. Hence, she had no evidence of leukemia but rather had leukostasis from a spider bite. Hydroxyurea was stopped and follow-up labs normalized. Sphingomyelinase D in the brown recluse spider venom is unique to Loxosceles and Sicarius and may be responsible for the unique clinical presentation of loxoscelism. The presentation of hyperleukocytosis complicated by shock with an unclear history poses a diagnostic challenge. In diagnostic uncertainty, consider delaying chemotherapy until a diagnosis can be confirmed to avoid potential harm.
Assuntos
Leucostasia , Picada de Aranha , Adulto , Animais , Aranha Marrom Reclusa , Feminino , Humanos , Picada de Aranha/complicações , Picada de Aranha/diagnóstico , Adulto JovemRESUMO
Diabetic retinopathy is one of the leading causes of vision loss and blindness. Extensive preclinical and clinical evidence exists for both vascular and neuronal pathology. However, the relationship of these changes in the neurovascular unit and impact on vision remains to be determined. Here, we investigate the role of tight junction protein occludin phosphorylation at S490 in modulating barrier properties and its impact on visual function. Conditional vascular expression of the phosphorylation-resistant Ser490 to Ala (S490A) form of occludin preserved tight junction organization and reduced vascular endothelial growth factor (VEGF)-induced permeability and edema formation after intraocular injection. In the retinas of streptozotocin-induced diabetic mice, endothelial-specific expression of the S490A form of occludin completely prevented diabetes-induced permeability to labeled dextran and inhibited leukostasis. Importantly, vascular-specific expression of the occludin mutant completely blocked the diabetes-induced decrease in visual acuity and contrast sensitivity. Together, these results reveal that occludin acts to regulate barrier properties downstream of VEGF in a phosphorylation-dependent manner and that loss of inner blood-retinal barrier integrity induced by diabetes contributes to vision loss.
Assuntos
Barreira Hematorretiniana/fisiologia , Diabetes Mellitus Experimental/fisiopatologia , Retinopatia Diabética/fisiopatologia , Ocludina/fisiologia , Acuidade Visual , Animais , Leucostasia/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Fosforilação , Estreptozocina , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
Hyperleukocytosis has been associated with early mortality owing to the presence of complications including leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC). Leukapheresis is a fast and effective cytoreductive procedure that removes leukocytes from the peripheral circulation. This single-center, retrospective, and observational study included 32 patients diagnosed with acute leukemia who underwent leukapheresis due to hyperleukocytosis between 2014 and 2020. This study primarily aimed to investigate the effect of prophylactic leukapheresis on early mortality and overall survival (OS). In the symptomatic group, seven and two patients died in the first and second weeks, respectively. In the prophylactic leukapheresis group, two and one patients died in the first and second weeks (p = 0.792), respectively. OS was significantly longer in the prophylactic leukapheresis group (p = 0.004). The leukapheresis procedure appears to be effective on early mortality and OS. Initiation of prophylactic leukapheresis before the appearance of leukostasis symptoms is effective on OS and possibly early mortality.