RESUMO
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global healthcare crisis. While SARS-CoV-2-associated COVID-19 affects primarily the respiratory system, patients with COVID-19 frequently develop extrapulmonary manifestations. Notably, changes in the hematological system, including lymphocytopenia, neutrophilia and significant abnormalities of hemostatic markers, were observed early in the pandemic. Hematological manifestations have since been recognized as important parameters in the pathophysiology of SARS-CoV-2 and in the management of patients with COVID-19. In this narrative review, we summarize the state-of-the-art regarding the hematological and hemostatic abnormalities observed in patients with SARS-CoV-2-associated COVID-19, as well as the current understanding of the hematological system in the pathophysiology of acute and chronic SARS-CoV-2-associated COVID-19.
Assuntos
COVID-19 , Hemostáticos , Humanos , SARS-CoV-2 , PandemiasRESUMO
BACKGROUND: Multiple Myeloma (MM) is a haematological malignancy with increasing global incidence. Diagnosis of MM should be initiated at the primary care level to achieve the best patient outcome. However, this can be delayed due to nonspecific presenting symptoms, such as back pain and fatigue. OBJECTIVES: The aim of this study was to investigate if commonly requested blood tests could indicate MM in primary care and potentially lead to earlier diagnosis. DESIGN AND METHODS: This retrospective observational study involved an audit of clinical and laboratory data from 109 MM patients, including patients with Active MM (N = 53), Smouldering MM (N = 33), and Free light chain MM (N = 23). RESULTS: Of the 16 potential biomarkers investigated, the most promising indicator for early detection of active MM and Smouldering MM was an increased Calculated Globulin (CG). The median CG for patients with active MM (50 g/L) was 78.6% higher than the healthy control group (28 g/L). Smouldering MM patients had a median CG value (38 g/L), which was 35.7% higher than the control group. Of interest, the median CG result was only 16.7% higher in the control group than in the free light chain MM group, suggesting CG would not be as effective at detecting this subtype. CONCLUSIONS: CG is derived from Total Protein and Albumin data, which are commonly measured in routine liver function profiles, thus there is no additional test or cost requirement. Based on these data, CG has potential as a clinical biomarker to support early detection of MM at the primary care level and allow for appropriate targeted investigations.
Assuntos
Globulinas , Mieloma Múltiplo , Paraproteinemias , Mieloma Múltiplo Latente , Humanos , Mieloma Múltiplo/diagnóstico , Paraproteinemias/diagnóstico , Estudos Retrospectivos , Diagnóstico PrecoceRESUMO
In recent years, the life expectancy of Multiple Myeloma (MM) patients has substantially improved, but this cancer remains incurable with increasing incidence in the developed world. Most MM patients will eventually relapse due to residual drug-resistant cancerous cells that survive treatment, commonly referred to as minimal residual disease (MRD). Methods to improve MRD detection in MM patients are generating considerable interest as a means of monitoring patients' response to treatment. In clinical laboratories, these methods currently require bone marrow aspirates which are invasive and frequently miss detection of localised disease due to the spatial heterogeneity of disease infiltration. By simplifying serial sampling and allowing for the detection of extramedullary disease, a blood-based method could significantly impact treatment duration and intensity and minimise chemotherapy-induced toxicity. This review will describe the current blood-based techniques available to detect MRD in MM and compare their potential to evaluate patient prognosis and drive therapeutic decisions.
Assuntos
Citometria de Fluxo/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Espectrometria de Massas/métodos , Mieloma Múltiplo/complicações , Neoplasia Residual/etiologia , Humanos , Mieloma Múltiplo/patologia , Neoplasia Residual/fisiopatologiaAssuntos
COVID-19 , Diabetes Mellitus , Animais , Humanos , Lisina , Metabolômica , Monócitos , Neutrófilos , Ratos , Estudos Retrospectivos , SARS-CoV-2Assuntos
Proteínas de Fusão bcr-abl/análise , Hematopoese Extramedular , Células-Tronco Hematopoéticas/patologia , Leucemia Mieloide de Fase Crônica/diagnóstico , Células-Tronco Neoplásicas/patologia , Derrame Pericárdico/patologia , Líquido Pericárdico/fisiologia , Pericardite/patologia , Idoso , Biomarcadores Tumorais , Linhagem da Célula , Feminino , Células-Tronco Hematopoéticas/química , Humanos , Leucemia Mieloide de Fase Crônica/complicações , Leucemia Mieloide de Fase Crônica/patologia , Leucocitose/etiologia , Células-Tronco Neoplásicas/química , Derrame Pericárdico/complicações , Líquido Pericárdico/química , Líquido Pericárdico/citologia , Pericardite/complicaçõesRESUMO
Here we describe a rare case of renal myeloid sarcoma, first discovered incidentally on routine urine analysis, which is one of the first of it's kind to be reported. We describe the vanishingly rare phenomenon of renal myeloid sarcoma presenting without haematological manifestation while also highlighting the often inevitable transformative nature of the disease. We also describe the unusual immunohistochemistry findings, in particular the cytokeratin expression, that is not usually typical of such cases. We briefly discuss use of PET-CT for the disease response monitoring. We summarize treatment that has included palbociclib, use of which was previously reported only in small series of patients with AML with KMT2A mutation.
Assuntos
Leucemia Mieloide Aguda , Sarcoma Mieloide , Humanos , Queratinas , Neoplasias Renais , Leucemia Mieloide Aguda/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/tratamento farmacológico , Neoplasias de Tecidos MolesRESUMO
Thrombotic events are common in patients with multiple myeloma (MM), smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS). Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC-1 antibody (specific for activated integrin αIIbß3) binding were significantly elevated in patients with MGUS versus the HCs. These markers were also elevated in SM/MM, but not significantly. In all, 74% of MGUS and 38% of SM/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker-specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor-activating peptide 6] stimulation in vitro was observed, with significantly reduced surface levels of P-selectin in response to ADP in patients with MGUS. Platelet-leucocyte aggregates were not altered in patients, while platelet-associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada/complicações , Mieloma Múltiplo/complicações , Ativação Plaquetária , Trombose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Feminino , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Trombose/sangue , Trombose/patologiaAssuntos
Janus Quinase 2/genética , Transtornos Mieloproliferativos/diagnóstico , Trombocitemia Essencial/diagnóstico , Substituição de Aminoácidos , Humanos , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologiaAssuntos
Medula Óssea , Neoplasias Hematológicas , Hidroxiureia/administração & dosagem , Leucostasia , Doenças Mieloproliferativas-Mielodisplásicas , Pirazóis/administração & dosagem , Idoso , Medula Óssea/metabolismo , Medula Óssea/patologia , Evolução Fatal , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Leucostasia/tratamento farmacológico , Leucostasia/metabolismo , Leucostasia/patologia , Masculino , Doenças Mieloproliferativas-Mielodisplásicas/tratamento farmacológico , Doenças Mieloproliferativas-Mielodisplásicas/metabolismo , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Nitrilas , PirimidinasAssuntos
Síndromes Mielodisplásicas/diagnóstico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Resultado do TratamentoRESUMO
The standard diagnosis of multiple myeloma by flow cytometry is based on selection of population of CD38+/CD138+ positives cells. As the result treatment with proteasome inhibitors, CD138 may be underexpressed on atypical plasma cells. Thus, in order to improve this strategy, recently new CD138-independent method, based on CD38 positivity of plasma cells was developed. We present an unusual case of CD138- negative multiple myeloma which had become double CD138-/CD38- negative after treatment with daratumumab by which we would like to illustrate potential pitfalls of both strategies.
Assuntos
ADP-Ribosil Ciclase 1 , Anticorpos Monoclonais/administração & dosagem , Glicoproteínas de Membrana , Mieloma Múltiplo , Proteínas de Neoplasias , Inibidores de Proteassoma/administração & dosagem , Sindecana-1 , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Plasmócitos/metabolismo , Plasmócitos/patologiaRESUMO
We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft.