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1.
Toxicol Lett ; 318: 92-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678399

RESUMO

Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48 h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2nd and 4th days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4th and 5th days. Thrombocytopenia was observed in 75% of patients between 4th and 6th days for mild cases and between 9th and 11th days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11th and 12th days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.


Assuntos
Medula Óssea/efeitos dos fármacos , Terrorismo Químico , Substâncias para a Guerra Química/envenenamento , Leucocitose/induzido quimicamente , Leucopenia/induzido quimicamente , Linfopenia/induzido quimicamente , Gás de Mostarda/envenenamento , Trombocitopenia/induzido quimicamente , Adolescente , Adulto , Biomarcadores/sangue , Medula Óssea/patologia , Feminino , Hemoglobinas/metabolismo , Humanos , Leucocitose/sangue , Leucocitose/patologia , Leucopenia/sangue , Leucopenia/patologia , Linfopenia/sangue , Linfopenia/patologia , Masculino , Síria , Trombocitopenia/sangue , Trombocitopenia/patologia , Adulto Jovem
2.
Medicine (Baltimore) ; 98(46): e17701, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725613

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) which involves multiple organ systems, including lungs. However, there is limited data on lung involvement of SFTS. Therefore, the present study investigated the chest radiographic findings of SFTS, including computed tomography (CT), and compared these with those of scrub typhus, which is the most common tick-borne illness in South Korea and share risk factors and occur in similar settings.Medical records of patients with confirmed SFTS and scrub typhus in a tertiary hospital in Seoul (South Korea), between January 2014 and June 2018, were reviewed. Initial chest radiography and CT were reviewed by 2 experienced radiologists.A total of 39 patients with SFTS and 101 patients with scrub typhus were analyzed. All patients except 3 patients with scrub typhus in both groups received chest radiography. Cardiomegaly (90%) and patchy consolidation with ground glass opacity (GGO) pattern (31%) were more common in SFTS group than scrub typhus group (20%, P < .001 and 2%, P < .001, respectively). About half of each group received chest CT. Consolidation (29%) and pericardial effusion (24%) were more common in SFTS group than scrub typhus group (6%, P = .02 and 4%, P = .008, respectively). Interstitial thickening in chest radiography (58%) and chest CT (65%) was more frequent in scrub typhus group than SFTS group (18%, P < .001 and 19%, P < .001, respectively).Cardiomegaly with/without pericardial effusion and patchy consolidation with GGO pattern were more frequent in SFTS group, whereas interstitial thickening was more frequent in scrub typhus group. These findings will assist the early differentiation of SFTS from scrub typhus.


Assuntos
Orientia tsutsugamushi , Febre por Flebótomos/diagnóstico por imagem , Phlebovirus , Radiografia/estatística & dados numéricos , Infecções Respiratórias/diagnóstico por imagem , Tifo por Ácaros/diagnóstico por imagem , Idoso , Estudos Transversais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Febre por Flebótomos/microbiologia , Radiografia/métodos , República da Coreia , Infecções Respiratórias/microbiologia , Tifo por Ácaros/microbiologia , Síndrome , Trombocitopenia
4.
Medicine (Baltimore) ; 98(39): e17147, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574817

RESUMO

The study aims to examine the treatment effect and adverse reactions of patients with newly diagnosed MM receiving different bortezomib-based regimens.This was a retrospective study of patients with newly diagnosed MM and who were treated with bortezomib-based combined chemotherapy at the Department of Hematology of the 2 affiliated hospitals of Wenzhou Medical University between July 2009 and May 2016. Cox proportion hazard multivariate analyses were carried out to assess the differences in treatment effect and adverse events between standard (1.3 mg/m on days 1, 4, 8, 11) and weekly (1.6 mg/m on days 1, 8, 15) cohorts, as well as the differences between intravenous injection and subcutaneous injection therapy. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier method and the log-rank test.Among the 117 patients, 78 patients were treated with bortezomib standard therapy and 39 patients were treated with bortezomib weekly therapy (all with intravenous injection). In all patients, the treatment strategy was not independently associated with PFS or OS. The patients in the weekly therapy group had less thrombocytopenia events than those in the standard therapy group. The subcutaneous route had similar treatment effect as the intravenous route, but the incidence of peripheral neuropathy was lower.The once-weekly bortezomib regimen was similar in effectiveness to standard therapy in treating patients with newly diagnosed MM, but the incidence of thrombocytopenia was lower with the weekly regimen compared with the standard regimen.


Assuntos
Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Idoso , Antineoplásicos/efeitos adversos , Bortezomib/efeitos adversos , China , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(42): e17571, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626125

RESUMO

RATIONALE: Severe fever with thrombocytopenia syndrome (SFTS) is a recently recognized fatal infectious disease caused by the SFTS virus, and severe cases are complicated by the presence of hemophagocytic lymphohistiocytosis (HLH) associated with a cytokine storm. Herein, we report on serial changes of serum cytokine levels and viral load in a severe case of SFTS. PATIENT CONCERNS: A 63-year-old Japanese woman presented with high-grade fever, abdominal pain, diarrhea, impaired consciousness, leukocytopenia, and thrombocytopenia. DIAGNOSIS: SFTS was diagnosed based on a positive serum test for SFTS virus RNA and electroencephalogram (EEG) findings of encephalopathy. INTERVENTIONS: The patient was treated with supportive therapy, including steroid pulse therapy (intravenous methylprednisolone 1 g/d for 3 days) for HLH and intravenous recombinant thrombomodulin 19200 U/d for 7 days for disseminated intravascular coagulation. OUTCOMES: Treatment for 7 days improved both symptoms and abnormal EEG findings, and SFTS virus RNA disappeared from the serum at day 10 from the onset of symptoms. The serum cytokines and chemokines analysis during the clinical course revealed 2 distinct phases: the acute phase and the recovery phase. The cytokines and chemokines elevated in the acute phase included interleukin (IL)-6, IL-10, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, interferon-γ-induced protein-10, and fractalkine, while the IL-1ß, IL-12p40, IL-17, and vascular endothelial growth factor levels were higher in the recovery phase. CONCLUSION: These observations suggest that the cytokines and chemokines elevated in the acute phase may reflect the disease severity resulted in a cytokine storm, while those in the recovery phase may be attributed to T-cell activation and differentiation.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Febre/sangue , Febre por Flebótomos/sangue , Phlebovirus/fisiologia , Trombocitopenia/sangue , Carga Viral , Biomarcadores/sangue , Feminino , Febre/virologia , Humanos , Pessoa de Meia-Idade , Febre por Flebótomos/virologia , Índice de Gravidade de Doença , Síndrome , Trombocitopenia/virologia
8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1108-1112, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657334

RESUMO

OBJECTIVE: To investigate the effect of recombinant human thrombopoietin (rhTPO) on thrombocytopenia (TCP) induced by endotoxin lipopolysaccharide (LPS) in mice. METHODS: Sixty male C57BL/6 mice were divided into normal saline (NS) control group (NS group), sepsis-induced TCP model group (LPS group) and rhTPO treatment group (LPS+rhTPO group) by random number table with 20 mice in each group. Sepsis-induced TCP model was reproduced by one intraperitoneal injection of LPS 30 mg/kg, and the mice in NS group were given the same amount of NS. In LPS+rhTPO group, 2.7 kU/kg rhTPO was subcutaneously injected into mice immediately after intraperitoneal injection of LPS, once every 24 hours. The mice in NS group and LPS group were injected subcutaneously with the same amount of NS. The observation period of each group lasted for 72 hours. The inner canthus blood was harvested before and every 24 hours after modeling, and the platelet count (PLT) was measured by animal blood cell counter. The eyeball blood of mice was harvested at 72 hours after modeling, and the proportion of CD61+CD62p+ cells in platelet-rich plasma was detected by flow cytometry, by which the platelet activation was reflected. Lung and spleen tissues of mice were harvested, and the positive expression of CD41 was determined by immunohistochemistry, by which the platelet sequestration in organs was reflected. Bone marrow cells from unilateral femur of mice were harvested, and the proportion of CD41+CD61+ cells was determined by flow cytometry to reflect the proliferation of bone marrow megakaryocytes. RESULTS: There was no significant difference in PLT among the groups before modeling. With the extension of the time after modeling, PLT in LPS group was decreased continuously, and increased slightly at 72 hours, but it was still significantly lower than that in NS group (×109/L: 308.60±21.70 vs. 1 152.72±50.27, P < 0.05); PLT in LPS+rhTPO group was increased continuously with the extension of modeling time, and it was significantly higher at 72 hours than that in LPS group (×109/L: 926.78±48.85 vs. 308.60±21.70, P < 0.05). At 72 hours after modeling, the proportion of CD61+CD62p+ cells in platelet-rich plasma of LPS group was significantly higher than that of NS group [(25.07±2.55)% vs. (4.17±0.38)%, P < 0.05], while the value in LPS+rhTPO group was significantly lower than that of LPS group [(15.92±1.26)% vs. (25.07±2.55)%, P < 0.05]. The proportion of CD41+CD61+ cells in bone marrow megakaryocytes of LPS group was significantly higher than that of NS group [(11.84±0.80)% vs. (3.60±0.42)%, P < 0.05], and the proportion of CD41+CD61+ cells in LPS+rhTPO group was significantly higher than that in LPS group [(30.96±2.49)% vs. (11.84±0.80)%, P < 0.05]. Immunohistochemistry showed that the positive expressions of CD41 in lung and spleen tissues of LPS group increased significantly than NS group [A value: 828.94±119.30 vs. 447.09±16.19 in lung tissue, (280.15±16.71)×103 vs. (0.65±0.26)×103 in spleen tissue, both P < 0.05], while the positive expressions of CD41 in lung and spleen tissues of LPS+rhTPO group decreased significantly than LPS group [A value: 542.78±2.95 vs. 828.94±119.30 in lung tissue, (129.40±13.49)×103 vs. (280.15±16.71)×103 in spleen tissue, both P < 0.05]. CONCLUSIONS: The rhTPO in endotoxin-induced TCP may stimulate the proliferation of bone marrow megakaryocytes, inhibit platelet activation and affect platelet sequestration in organs, so as to increase platelet levels.


Assuntos
Trombocitopenia , Trombopoetina , Animais , Plaquetas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Plaquetas , Proteínas Recombinantes
9.
FP Essent ; 485: 32-43, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31613566

RESUMO

Platelets have an important role in hemostasis. Platelet disorders occur when too few or too many platelets are present, or when platelet functions are abnormal. Thrombocytopenia, defined as a platelet count less than 150,000/mcL, can be acute or chronic and congenital or acquired. Severe thrombocytopenia is associated with life-threatening bleeding and thrombotic complications. A comprehensive history and physical examination are central to the diagnostic approach. These elements should focus on identification of concurrent conditions associated with thrombocytopenia and differentiation among three mechanisms: decreased platelet production, increased platelet consumption, and platelet sequestration. Although previously thought to be the result of a single process, thrombocytopenia often is due to a combination of factors. Thrombocytosis is present when the platelet count is elevated. The principal types are essential (primary) thrombocythemia and reactive (secondary) thrombocytosis. Essential thrombocythemia is a myeloproliferative neoplasm associated with mutations of genes that regulate thrombopoiesis (eg, JAK2). It can lead to thrombotic and hemorrhagic complications. Reactive thrombocytosis frequently is encountered in the family medicine setting. It rarely causes vascular complications or requires management beyond that required for the underlying condition. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.


Assuntos
Anemia , Trombocitopenia , Trombocitose , Anemia/diagnóstico , Anemia/terapia , Plaquetas , Humanos , Contagem de Plaquetas , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Trombocitose/diagnóstico , Trombocitose/terapia
10.
Autoimmun Rev ; 18(11): 102395, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520800

RESUMO

BACKGROUND: According to criteria for the classification of Systemic Lupus Erythematosus (SLE), thrombocytopenia is one of the disease-defining hematologic disorders. Since the recognition of Antiphospholipid Syndrome (APS), thrombocytopenia was frequently reported but several studies yielded contradictory results on the association between aPL-positivity and thrombocytopenia. METHODS: We evaluated the role of antiphospholipid antibodies (aPL) and different aPL profiles on the risk of thrombocytopenia in SLE patients by conducting a systematic review and meta-analysis of available literature from 1987 to 2018. MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (thrombocytopenia). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis. PROSPERO registration number: CRD42015027378. RESULTS: From 3278 articles identified, 53 studies met inclusion criteria amounting to 9019 SLE patients. Twenty-nine percent of aPL-positive SLE patients had thrombocytopenia compared to 15.1% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for thrombocytopenia in aPL positive patients was 2.48 (95% CI; 2.10-2.93). Among aPL subtypes, the risk of thrombocytopenia was highest for lupus anticoagulant (OR = 3.56 [95% CI, 2.57-5.25]), IgM anti-ß2-GP1(OR = 2.87 [95% CI; 2.57-5.25]), IgG and IgM anticardiolipin antibodies (OR = 1.87 [95% CI; 1.52-2.31] and OR = 1.73 [95% CI; 1.36-2.19] respectively). CONCLUSIONS: The occurrence of thrombocytopenia was strongly determined by various aPL profiles in SLE patients. While the association between IgM antibodies and other APS manifestations including thrombosis is debated, IgM isotypes are helpful in the risk stratification of thrombocytopenia in SLE.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Trombocitopenia/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Risco , Trombocitopenia/imunologia
11.
J Assoc Physicians India ; 67(7): 61-64, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559771

RESUMO

Objective: To study the incidence of thrombocytopenia in adults with Plasmodium vivax infection. Method: An observational study comprising 84 consenting individuals with Plasmodium vivax infection was undertaken. All the individuals belong to armed forces who are from different parts of the country. Everyone had normal platelet count prior to admission to the hospital. After admission, they were subjected to routine hematological and biochemical investigations comprising complete blood count including platelet counts, urine routine, liver function test, renal function test, serum electrolytes and Chest X-ray after ruling out Dengue, concomitant sepsis and possibility of recent viral infection. Grading of thrombocytopenia was done according to NCI common terminology criteria for adverse events Version 3.0. Results were analysed and tabulated. Result: A total of 84 patients were studied. 82 (97.6%) patients had thrombocytopenia. Majority (68.3%) of the patients had their lowest platelet count on the 5th and 6th day of fever. There was no associated increase in risk of complication with the increase in grade of thrombocytopenia. But with increase in severity of thrombocytopenia, it took more time for the platelets to recover to normal level. Conclusion: Thrombocytopenia is widely present in P. vivax malaria of adults. However, the severity of thrombocytopenia does not correlate with the likely progression to complication. The chance of progressing to complicated malaria is equal among all adults of P.vivax malaria irrespective of the platelet levels. Hence, in a resource limited rural Indian set-up where the expertise to diagnose and detect malaria microscopically or reliable antigen detection method is not available, thrombocytopenia in an acute febrile illness especially on Day 5 to Day 6 of fever onset could be considered as P. vivax malarial infection with good amount of diagnostic accuracy (sensitivity of 97.6%) and empirical anti-malarial therapy could be started as per the existing treatment guidelines.


Assuntos
Malária Vivax/epidemiologia , Trombocitopenia/epidemiologia , Adulto , Plaquetas , Humanos , Malária , Malária Vivax/diagnóstico , Contagem de Plaquetas
12.
Int J Clin Pharmacol Ther ; 57(12): 607-611, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31488241

RESUMO

The anti-programmed cell death-ligand 1 (PD-L1) antibody atezolizumab is a promising agent for various cancers. Although immune-related adverse events (irAEs) induced by atezolizumab are rare, they can be severe. Clinical experience in irAE management is presently insufficient. Herein, we present a case of a patient with non-small cell lung cancer (NSCLC) who developed life-threatening irAEs including pneumonitis, thrombocytopenia, and cardiac dysfunction under immunotherapy with atezolizumab. Under expectant treatment and corticosteroid regimen, pneumonitis was totally resolved. However, thrombocytopenia and cardiac dysfunction did not improve. The patient sadly passed away 28 days after a single dose of atezolizumab. This case alarmed us once more to the importance of irAE management under cancer immunotherapy.
.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Cardiopatias/complicações , Neoplasias Pulmonares/terapia , Pneumonia/complicações , Trombocitopenia/complicações , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Evolução Fatal , Humanos , Imunoterapia , Neoplasias Pulmonares/complicações
13.
BMC Infect Dis ; 19(1): 780, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492102

RESUMO

BACKGROUND: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. METHODS: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. DISCUSSION: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.


Assuntos
Sepse/complicações , Sepse/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Doença Aguda , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Contagem de Plaquetas , Proteínas Recombinantes/uso terapêutico , Terapia de Salvação , Sepse/sangue , Sepse/mortalidade , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/mortalidade , Resultado do Tratamento , Adulto Jovem
14.
Niger J Clin Pract ; 22(8): 1120-1125, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31417056

RESUMO

Aim: Wilson's disease (WD) presents with different phenotypes. Neurologic and liver involvement in WD are well documented. Few reports demonstrated cardiac and vascular involvement. Several studies showed an association between serum copper levels and atherosclerosis. Although WD is the prototype disease of copper metabolism, atherosclerosis has not been studied yet. The aim of this study is to assess aortic stiffness in WD. Materials and Methods: Aortic pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx), central aortic systolic, diastolic, mean, and pulse pressures were measured using SphygmoCor (AtCor Medical) device in 32 patients with WD and 24 healthy controls. Results: Patients with WD and healthy controls were similar in terms of age sex, body mass index (BMI), and liver and kiney functions. However, patients with WD were anemic and thrombocytopenic. Echocardiographic parameters including left ventricular, atrial dimensions, and systolic and diastolic functions were similar between two groups. Patients with WD and healthy controls were compared. Baseline characteristics including age, sex, and BMI did not differ between groups. Central aortic systolic, diastolic, mean, and pulse pressures were similar between the groups. AP, AIx, and PWV did not differ between groups as well. Conclusion: Aortic stiffness in WD was similar in healthy controls.


Assuntos
Pressão Sanguínea/fisiologia , Cobre/metabolismo , Ecocardiografia/métodos , Degeneração Hepatolenticular/diagnóstico por imagem , Análise de Onda de Pulso , Rigidez Vascular/fisiologia , Adulto , Anemia/epidemiologia , Pressão Arterial , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Degeneração Hepatolenticular/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Trombocitopenia/epidemiologia , Turquia/epidemiologia
15.
Int J Clin Pharmacol Ther ; 57(10): 500-505, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426902

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of low-dose rituximab in the treatment of hematologic abnormalities in patients with connective tissue disease. MATERIALS AND METHODS: A total of 13 patients with connective tissue disease who did not respond to prednisolone and multiple immunosuppressive agents, or their disease recurred after treatment, were given 100 mg of rituximab only combined with prednisolone once a week for 4 weeks. Then, the therapeutic effects and adverse reactions were respectively observed in the 13 patients. RESULTS: Rituximab showed good and rapid efficacy in the treatment of refractory thrombocytopenia and autoimmune hemolytic anemia caused by systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. Only 1 patient had urinary tract infection. During 24-month follow-up, disease recurred in 7 patients who still responded to azathioprine/Tripterygium wilfordii. CONCLUSION: Low-dose rituximab has good efficacy and safety in the treatment of hematologic abnormalities in patients with connective tissue disease.


Assuntos
Doenças do Tecido Conjuntivo/tratamento farmacológico , Rituximab/uso terapêutico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/etiologia , Anticorpos Monoclonais Murinos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Sjogren/complicações , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Resultado do Tratamento
16.
N Engl J Med ; 381(6): 531-542, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390500

RESUMO

BACKGROUND: Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels. METHODS: We conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome. Patients were randomly assigned, in a 1:1 ratio, to receive volanesorsen or placebo. The primary end point was the percentage change in fasting triglyceride levels from baseline to 3 months. RESULTS: Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase (P<0.001). Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval [CI], 1330 to 2094 mg per deciliter [15.0 to 23.6 mmol per liter]), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, -301.0 to 486 mg per deciliter [-3.4 to 5.5 mmol per liter]) (P<0.001). At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter). A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions. No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter. No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began. CONCLUSIONS: Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection-site reactions were common adverse events. (Funded by Ionis Pharmaceuticals and Akcea Therapeutics; APPROACH Clinical Trials.gov number, NCT02211209.).


Assuntos
Apolipoproteína C-III/antagonistas & inibidores , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , RNA Mensageiro/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Triglicerídeos/sangue , Adulto , Idoso , Análise de Variância , Apolipoproteína C-III/sangue , Apolipoproteína C-III/genética , Método Duplo-Cego , Feminino , Humanos , Hiperlipoproteinemia Tipo I/sangue , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Contagem de Plaquetas , Adulto Jovem
17.
Ann Hematol ; 98(10): 2299-2302, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444663

RESUMO

Iron deficiency anemia (IDA) is often associated with mild to moderate thrombocytosis, and iron deficiency-associated thrombocytopenia (IDAT) is much more uncommon and often misdiagnosed as immune thrombocytopenia (ITP). To better describe the features of IDAT, we conducted a retrospective multicenter case-control study. We identified 10 patients (9 women) with a definite diagnosis IDAT, with a median age of 43.5 [range, 16-72] years and a median platelet count of 30.5 × 109/L [range, 21-80], and 7 patients with a possible diagnosis of IDAT. Bleeding manifestations were absent in all patients but one. All the patients recovered (platelet count ≥ 150 × 109/L) upon iron therapy ± red blood cell transfusion after a median time of 6 [4-39] days. When compared with 30 randomly newly diagnosed ITP patients matched on age, the baseline platelet count was significantly lower in ITP (median = 7 × 109/L [4-59], p < 0.001) whereas MPV was higher (10.5 fL [9,4-13,8] vs 8.2 fL, for IDAT p < 0.001). The median platelet count on day 7 was 337 × 109/L [113-1000] for IDAT cases vs 72 × 109/L [13-212] for ITP controls (p < 0.001). IDAT is potentially an under-recognized cause of thrombocytopenia that may be easily managed with iron therapy.


Assuntos
Anemia Ferropriva , Trombocitopenia , Adolescente , Adulto , Fatores Etários , Idoso , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etiologia , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
18.
Medicine (Baltimore) ; 98(35): e16993, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464949

RESUMO

RATIONALE: Parvovirus B19 (PV) infection is usually symptomless and can cause benign, short-lived conditions. Anemia associated with PRCA is the most representative hematologic manifestation, but neutropenia and thrombocytopenia have been rarely reported. PATIENT CONCERNS: Three patients were admitted to the hospital with neutropenia and thrombocytopenia. The accompanying symptoms were fever, myalgia, rash, or arthralgia, and all patients were previously healthy. DIAGNOSIS: Patients were positive for PV PCR and diagnosed with PV infection. Before the diagnosis of PV infection, 2 patients underwent BM study and almost absence of erythroid progenitor cells in BM aspiration were a clue for the PV infection. Other BM findings were hypocellular marrow and a few hemophagocytic histiocytes. INTERVENTIONS: Patients received supportive care with follow-up of CBC. OUTCOMES: All 3 patients spontaneously recovered from neutropenia and thrombocytopenia within 3 weeks without severe complications. LESSONS: The evaluation of PV infection should be considered in situations where there is neutropenia and thrombocytopenia in healthy individuals even without anemia as a differential diagnosis.


Assuntos
Neutropenia/complicações , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/diagnóstico , Trombocitopenia/complicações , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano , Reação em Cadeia da Polimerase
19.
N Engl J Med ; 381(8): 727-738, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433920

RESUMO

BACKGROUND: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Hidrazinas/administração & dosagem , Carioferinas/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Triazóis/administração & dosagem , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/sangue , Dexametasona/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Hidrazinas/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Triazóis/efeitos adversos , Adulto Jovem
20.
Einstein (Sao Paulo) ; 17(4): eAO4720, 2019 Aug 19.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31433009

RESUMO

OBJECTIVE: To verify the adequacy of platelet concentrate prescription by pediatricians in different pediatric sectors of a general hospital. METHODS: A cross-sectional study evaluating 218/227 platelet concentrate records in children and adolescents (zero to 13 years old), from January 2007 to April 2015, by the pediatricians of the emergency room, sick bay and intensive care unit. The requisitions were excluded in patients with hematological diseases and those without the number of platelets. RESULTS: Children under 12 months received 98 platelet concentrates (45.2%). Most of the transfusions were prophylactic (165; 79%). Regarding the transfusion site, 39 (18%) were in the emergency room, 27 (12.4%) in the sick bay and 151 (69.6%) in the intensive care unit. The trigger, prescribed volume and platelet concentrate subtype were adequate in 59 (28.2%), 116 (53.5%) and 209 (96.3%) of the transfusions, respectively. Patients with hemorrhage presented adequacy in 42 (95.5%), while children without bleeding presented in 17 (10.3%). The most common inadequacy related to volume was the prescription above recommendation (95; 43.8%). Eight platelet concentrates were prescribed with subtype requests without indication. CONCLUSION: The results obtained in this study showed that transfusion of platelet concentrate occurred more adequately in children with active bleeding compared to prophylactic transfusion. There was a tendency to prescribe high volumes and platelet subtypes not justified according to current protocols. The teaching of transfusion medicine should be more valued at undergraduate and medical residency.


Assuntos
Transfusão de Plaquetas/estatística & dados numéricos , Prescrições/normas , Trombocitopenia/terapia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Centros de Atenção Terciária , Trombocitopenia/prevenção & controle
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