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1.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
2.
Blood Adv ; 4(13): 2967-2978, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32609845

RESUMO

Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications.


Assuntos
Plaquetas/virologia , Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Trombocitopenia/etiologia , Animais , Plaquetas/metabolismo , Plaquetas/patologia , Modelos Animais de Doenças , Furões , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza A Subtipo H3N2/fisiologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Influenza Humana/patologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Trombocitopenia/metabolismo , Trombocitopenia/patologia , Trombocitopenia/virologia , Internalização do Vírus
3.
Mem Inst Oswaldo Cruz ; 115: e200080, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32696915

RESUMO

BACKGROUND: Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE: To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS: Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS: Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1ß and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS: Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.


Assuntos
Subpopulações de Linfócitos/imunologia , Malária Vivax/imunologia , Malária Vivax/patologia , Plasmodium vivax/imunologia , Trombocitopenia/sangue , Trombocitopenia/patologia , Humanos , Interleucina-12/sangue , Interleucina-2/sangue , Malária Vivax/sangue , Malária Vivax/parasitologia , Trombocitopenia/parasitologia
4.
Anticancer Res ; 40(6): 3361-3370, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487632

RESUMO

BACKGROUND/AIM: We evaluated whether splenic volume (SV) predicts sinusoidal obstruction syndrome (SOS) in colorectal cancer (CRC) patients receiving capecitabine plus oxaliplatin (CapeOX) therapy. PATIENTS AND METHODS: In this retrospective study, we measured SV in 41 patients receiving adjuvant CapeOX for CRC at five different time points. We compared the clinical data of the 18 patients who experienced ≥30% increases in SV immediately after vs. before CapeOX (group A) with data for the remaining 23 patients (group B). RESULTS: Platelet numbers decreased and the levels of hepatobiliary enzymes increased significantly 1 year after CapeOX compared with before CapeOX in group A. However, in group B, significantly decreased platelet numbers and significantly increased aspartate transaminase levels were confirmed only immediately after CapeOX, with no significant subsequent changes. CONCLUSION: SV was significantly associated with thrombocytopenia and liver dysfunction in CRC patients, and predicted SOS.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Hepatopatias/etiologia , Oxaliplatina/efeitos adversos , Baço/patologia , Trombocitopenia/induzido quimicamente , Antineoplásicos/farmacologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
6.
Ann Hematol ; 99(7): 1421-1428, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32495027

RESUMO

Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Progressão da Doença , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , China , Infecções por Coronavirus/patologia , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/patologia , Linfopenia/virologia , Masculino , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Trombocitopenia/virologia
7.
Ann Hematol ; 99(8): 1755-1762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32564195

RESUMO

The risk of lumbar puncture (LP) hemorrhagic complications is believed to be exacerbated by thrombocytopenia, yet evaluations in clinical practice are lacking. We conducted a retrospective cohort study to examine the risk of traumatic tap (TT) and significant hemorrhagic complications in thrombocytopenic patients undergoing bedside LP. Two hundred sixty-two adult patients undergoing initial bedside LP were analyzed. Overall, we observed 37 TTs (14.1%, 95% CI 10.0 to 18.3%). TTs occurred in 11 of 78 LPs performed on patients with thrombocytopenia, compared with 26 of 184 LPs among patients with a normal platelet count (14.1% vs 14.1%; p > 0.99) and 6 of 19 LPs among patients with severe thrombocytopenia compared with 31 of 243 among those without (31.6% vs 12.8%; p = 0.04). For patients with severe thrombocytopenia, the relative risk of TT was 2.5 (95% CI 1.2 to 5.2; p = 0.02). Stratifying this group by operator experience, a higher incidence of TTs was observed in LPs performed by trainees (57.1% vs 15.8%; p = 0.02), an effect which did not reach significance in LPs performed by dedicated procedural operators (16.7% vs 10.8%; p = 0.63). The presence of other bleeding risk factors was not found to be statistically associated with the incidence of TT. There were no significant hemorrhagic complications. TTs occurred significantly more frequently among patients with severe thrombocytopenia, an effect modulated by operator experience. For patients in this higher risk group, LPs should be performed by the most skilled operators available.


Assuntos
Perda Sanguínea Cirúrgica , Punção Espinal/efeitos adversos , Trombocitopenia/epidemiologia , Adulto , Idoso , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32366611

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 is a worldwide pandemic. The severe morbidity and mortality associated with coronavirus disease 2019 has mostly affected the elderly or those with underlying medical conditions. We present a case of a 12-year-old girl with no past medical history who presented with fever, cough, and vomiting. Laboratory evaluation revealed severe thrombocytopenia and elevated markers of inflammation. The patient progressed to respiratory failure, and testing results for the severe acute respiratory syndrome coronavirus 2 returned positive. Because of the severity of her thrombocytopenia, she was treated with intravenous immunoglobulin and steroids with prompt improvement in platelets. The patient's severe acute respiratory distress syndrome was managed with mechanical ventilation, inhaled nitric oxide, and then airway pressure release ventilation. After azithromycin and hydroxychloroquine were given without improvement, our patient received tocilizumab, an anti-interleukin-6 receptor antibody, and remdesivir, a broad antiviral agent, with significant clinical benefit soon afterward. Given that severe pediatric coronavirus disease 2019 is rare, we hope to inform pediatric providers on the clinical course and management considerations as this pandemic continues to spread.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/diagnóstico , Índice de Gravidade de Doença , Trombocitopenia/diagnóstico , Criança , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombocitopenia/etiologia , Trombocitopenia/terapia
10.
Crit Care ; 24(1): 205, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384917

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Oxigenação por Membrana Extracorpórea , Pneumonia Viral/terapia , Coagulação Sanguínea , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/terapia , Trombocitopenia
11.
Crit Care ; 24(1): 188, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32354360

RESUMO

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7-13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Lesão Renal Aguda/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China , Tosse/virologia , Feminino , Febre/virologia , Coração/virologia , Humanos , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , Prognóstico , Síndrome do Desconforto Respiratório do Adulto/virologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Trombocitopenia/virologia , Adulto Jovem
12.
BMC Infect Dis ; 20(1): 363, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448216

RESUMO

BACKGROUND: Plasmodium vivax rarely develops severe complications when compared to severe falciparum malaria. However, severe vivax malaria also needs urgent, intensive care and treatment as severe falciparum malaria. This systematic review aimed to explore pooled prevalence of severe vivax malaria and to identify factors related to poor outcome of patients who developed severe manifestation. METHODS: The systematic review conducted by two reviewers independently through searching of research publications related to severe P. vivax malaria in three databases including MEDLINE, Web of Science (ISI), and Scopus until October, 22 2019. The pooled prevalence of severe vivax malaria was achieved using STATA and RevMan 5 Software. Factors related to poor outcome of patients with severe vivax malaria were analyzed using SPSS 11.5 Software. RESULTS: Among 2615 research publications retrieved from three databases, 49 articles reporting on 42,325 severity cases were selected for calculating pooled prevalence. Seventy-six patients from case reports, case series, letter to editors, and research communications were collected to identify factors related to poor outcome of patients with severe vivax malaria. The results showed that severe anemia, jaundice, respiratory distress, impaired consciousness, and renal failure were the most common major manifestations of severe malaria guided by the World Health Organization (WHO) criterion. The meta-analysis indicated that severe malaria was less frequent in patient with P. vivax compared to those with P. falciparum (P -value < 0.00001, OR = 0.38, 95% CI = 0.25-0.56, I2 = 87%). In addition, thrombocytopenia, anemia, hepatitis, and severe thrombocytopenia were the most common minor complications. Analysis of cases indicated that convulsion, respiratory distress, renal failure, jaundice, anuria/oliguria, and complication during treatment impacted on longer hospital stays compared to other severe complications (P-value < 0.05). Respiratory distress was frequently found after first treatment with anti-malarial drugs (P-value = 0.002). Renal failure was frequently found before treatment with anti-malarial drugs (P-value = 0.016). Mean days of fever and higher pulse rates at presentation were predictors of poor outcome among patients with severe vivax malaria (P-value < 0.05). CONCLUSIONS: Severe anemia was the most common major manifestation of P. vivax malaria guided by the WHO criterion. Severe anemia was found less frequently in patients with P. vivax than those with P. falciparum. Renal failure, jaundice, anuria/oliguria, and complication during treatment along with, mean days of fever and higher pulse rates at presentation might be predictors of poor outcome of patients with severe vivax malaria.


Assuntos
Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Plasmodium falciparum , Plasmodium vivax , Índice de Gravidade de Doença , Adulto , Anemia/etiologia , Antimaláricos/uso terapêutico , Anuria/etiologia , Feminino , Febre , Frequência Cardíaca , Humanos , Icterícia/etiologia , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Malária Vivax/complicações , Malária Vivax/tratamento farmacológico , Malária Vivax/parasitologia , Masculino , Oligúria/etiologia , Prevalência , Insuficiência Renal/etiologia , Fatores de Risco , Trombocitopenia/etiologia , Resultado do Tratamento , Organização Mundial da Saúde , Adulto Jovem
13.
Lancet Haematol ; 7(6): e456-e468, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32359506

RESUMO

BACKGROUND: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING: Janssen and Celgene.


Assuntos
Quimioterapia de Consolidação/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Transplante Autólogo/métodos , Administração Intravenosa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Infecções/induzido quimicamente , Infecções/epidemiologia , Injeções Subcutâneas , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Proteínas do Mieloma/análise , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Plasmocitoma/patologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Transplante Autólogo/mortalidade
15.
Br J Haematol ; 190(2): 179-184, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32453877

RESUMO

Coronavirus disease 2019 (COVID-19) can affect the haematopoietic system. Thrombocytopenia at admission was prevalent, while late-phase or delayed-phase thrombocytopenia (occurred 14 days after symptom onset) is rare. This retrospective, single-centre study screened 450 COVID-19 patients and enrolled 271 patients at the Union Hospital, Wuhan, China, from January 25 to March 9, 2020. COVID-19-associated delayed-phase thrombocytopenia occurred in 11·8% of enrolling patients. The delayed-phase thrombocytopenia in COVID-19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed-phase thrombocytopenia is significantly associated with increased length of hospital stay and higher mortality rate. Delayed-phase nadir platelet counts demonstrated a significantly negative correlation with B cell percentages. We also provided and described bone marrow aspiration pathology of three patients with delayed-phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that immune-mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients. In addition, clinicians need to pay attention to the delayed-phase thrombocytopenia especially at 3-4 weeks after symptom onset.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Trombocitopenia/diagnóstico , Trombocitopenia/virologia , Adulto , Idoso , Betacoronavirus , Medula Óssea/patologia , China , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Estudos Retrospectivos
16.
Gan To Kagaku Ryoho ; 47(4): 646-648, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389971

RESUMO

We report a case of multiple lung metastasis of intrahepatic cholangiocarcinoma treated with chemotherapy, in which laparoscopic splenectomy was effective for thrombocytopenia. A 74-year-old woman was diagnosed with multiple lung metastasis of intrahepatic cholangiocarcinoma 6 years after partial liver resection(S3). She was undergoing treatment for post-transfusion hepatitis C infection since the age of 46 years and developed thrombocytopenia due to splenomegaly. The previous hospital determined that there was no indication for chemotherapy due to thrombocytopenia. Elective laparoscopic splenectomy resulted in an increase in the platelet count and facilitated the initiation of gemcitabine(GEM)and cisplatin (CDDP)combination chemotherapy. The patient has maintained a good treatment course without interruption due to thrombocytopenia during chemotherapy. In advanced cancer patients with thrombocytopenia complication due to splenomegaly, laparoscopic splenectomy may offer an effective auxiliary means for the safe implementation of chemotherapy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Laparoscopia , Neoplasias Pulmonares , Trombocitopenia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/terapia , Feminino , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Esplenectomia , Trombocitopenia/etiologia , Trombocitopenia/terapia
17.
BMC Infect Dis ; 20(1): 346, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410583

RESUMO

BACKGROUND: To analyze and discuss the transmission route of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). METHOD: We performed an epidemiological investigation and a genetic analysis of patients with severe fever with thrombocytopenia syndrome (SFTS) caused by SFTSV, their close contacts and the surrounding population. RESULTS: We found that all patients had contact with the blood of the first patient. The comparison of gene sequences in the three isolated SFTSV strains showed that the strains were closely related. Six close contacts and nine individuals in the surrounding population were positive for SFTSV IgM antibody. CONCLUSION: We suspect that the cluster outbreak was transmitted via blood and that the natural reservoir host of SFTSV exists in the patients' environment.


Assuntos
Infecções por Bunyaviridae/epidemiologia , Phlebovirus/genética , Idoso , Infecções por Bunyaviridae/virologia , China/epidemiologia , Surtos de Doenças , Fazendeiros , Humanos , Leucopenia/virologia , Masculino , Pessoa de Meia-Idade , Phlebovirus/isolamento & purificação , Trombocitopenia/virologia
19.
Acta Chir Orthop Traumatol Cech ; 87(2): 129-133, 2020.
Artigo em Tcheco | MEDLINE | ID: mdl-32396515

RESUMO

Heparin-induced thrombocytopenia is a rare complication of treatment with both unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Antibodies against the complex heparin-platelet factor 4 are the main cause of pathogenesis, resulting in the activation of thrombocytes, coagulation, endothelium, monocytes, neutrophils and subsequent highly prothrombotic state. The prothrombotic state can result not only in venous but also in arterial thrombosis at different locations (which is manifested apart from venous thromboembolic disease also by acute limb ischemia, acute myocardial infarction, ischemic stroke, skin necrotizing lesion exanthema). If HIT is not adequately treated, it may be fatal in up to 10% of patients. For early diagnosis, a combination of 4T scores and diagnostic lab tests for HIT is required. Immediate discontinuation of heparin therapy (UFH, LMWH) and switching to non-heparin anticoagulants (fondaparinux, bivalirudin, argatroban or in some situations DOACs) are essential in HIT treatment. The case report describes the patient after primary knee replacement, complicated by the development of HIT with no evidence of venous thromboembolic disease. Preoperatively, the patient was administrated nadroparin due to paroxysmal atrial fibrillation, after the development of HIT, anticoagulation was modified to fondaparinux and subsequently to warfarin after the platelet count normalization. Key words: unfractioned heparin, low molecular weight heparin, thrombocytopenia, total knee replacement.


Assuntos
Anticoagulantes/efeitos adversos , Artroplastia do Joelho , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Humanos , Trombocitopenia/diagnóstico , Trombocitopenia/terapia
20.
Medicine (Baltimore) ; 99(19): e20156, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384505

RESUMO

The effect of direct-acting antiviral agents (DAAs) on short-term platelet improvement in chronic hepatitis C (CHC) patients with thrombocytopenia is unclear.From December 2015 to March 2018, a total of 249 CHC patients receiving DAA treatment with baseline thrombocytopenia (platelet count <150 × 10 /µL) at Dalin Tzu Chi Hospital were enrolled in this retrospective study. Blood examinations were conducted at baseline (BL), week 4 (W4) after DAA initiation, end of treatment (EOT), and 12 weeks after EOT (P12).Hepatitis C virus (HCV) genotyping revealed that 184 patients (73.9%) carried HCV genotype 1. Of the patients in the cohort, 87 (34.9%) were interferon (IFN)-experienced, and 213 (85.5%) had advanced fibrosis. All but 1 patient achieved SVR12 (sustained virologic response (SVR) rate, 99.6%; 248/249). The platelet count recovered significantly in 104 patients (41.7%; 104/249). The mean baseline platelet count was 102 × 10/µL before DAA, increasing to 116 × 10/µL, 114 × 10/µL, and 113 × 10/µL at W4, EOT, and P12, respectively. Comparison of the mean platelet count at baseline with that at W4, EOT, and P 12 showed statistically significant increases at all time points (W4 vs BL, P < .001; EOT vs BL, P < .001; P12 vs BL, P < .001). Multivariate analyses revealed moderate or severe fatty liver (P = .024) and lower baseline platelet count (P = .005) was significantly associated with platelet count improvement.In conclusion, thrombocytopenia associated with CHC rapidly improves with the administration of DAA. Moderate or severe fatty liver and lower baseline platelet count predict significant improvement of platelet count.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Contagem de Plaquetas , Trombocitopenia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Testes Hematológicos , Humanos , Cirrose Hepática/epidemiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resposta Viral Sustentada , Trombocitopenia/sangue
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