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1.
Neurology ; 93(19): e1799-e1806, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31586022

RESUMO

OBJECTIVE: To determine the efficacy of the thrombopoietin receptor agonist romiplostim for the prevention of temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma. METHODS: In the PLATUM phase II open-label, multicenter, single-arm trial, patients diagnosed with Common Terminology Criteria for Adverse Events grade 3 or 4 thrombocytopenia during chemoradiotherapy received weekly subcutaneous romiplostim injections. PLATUM aimed at demonstrating that the percentage of thrombocytopenic patients treated with romiplostim able to complete 6 cycles of maintenance temozolomide chemotherapy exceeded 10% (p0 = 0.10; pA = 0.35). Using type I error equal to 0.05% and 95% power, 31 patients had to be recruited. According to a Fleming 2-step design with a preplanned interim analysis after recruitment of 20 patients (step 1), the trial was terminated early for success. RESULTS: Twenty patients were enrolled in step 1. Median age was 61 years (range 33-73). Twelve patients received 6 temozolomide cycles, corresponding to a success rate of 60% (95% confidence interval 36%-81%). Four patients discontinued temozolomide because they did not respond to romiplostim, 2 for progression, and 2 for adverse events unrelated to romiplostim. CONCLUSION: The thrombopoietin receptor agonist romiplostim improves exposure to chemotherapy in patients with glioblastoma experiencing temozolomide-induced thrombocytopenia. CLINICALTRIALSGOV IDENTIFIER: NCT02227576. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with glioblastoma and thrombocytopenia, romiplostim is effective for the secondary prophylaxis of temozolomide-induced thrombocytopenia.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Temozolomida/efeitos adversos , Trombocitopenia/prevenção & controle , Trombopoetina/uso terapêutico , Adulto , Idoso , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Trombopoetina/agonistas , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico
3.
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
4.
Hum Vaccin Immunother ; 15(10): 2249-2257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215838

RESUMO

Infection caused by the severe fever and thrombocytopenia syndrome virus (SFTSV) causes a hemorrhagic illness with a mortality between 20% and 40%. Initially recognized in 2009 in China, cases have additionally been documented in Japan and Korea although retrospective studies have documented seroprevalence since 1996. Although case rates have increased due to increased awareness and more widely available diagnostics, SFTSV infection remains rare with the highest rates documented in Korea for Jeju Province (3.5 cases per 100,000 population) and the Inje-gun region (66.2 cases per 100,000). Because of the very low incidence of infection, a placebo-controlled study with 1:1 randomization to evaluate an SFTSV vaccine would require a sample size that is 25% greater than the region of study. We discuss alternatives to licensure. Vaccine effectiveness may be assessed through a registry, comparing rates of infection over time between vaccine recipients versus regional populations. Modeled data can be updated based on actual case rates and population changes over the years of follow-up. Using one model, statistically significant differences are seen after 10 years in Inje-gun and 15 years of follow-up in Jeju. This approach may be applicable to other uncommon infectious diseases for which a standard study design is difficult.


Assuntos
Infecções por Bunyaviridae/epidemiologia , Febres Hemorrágicas Virais/epidemiologia , Doenças Raras/virologia , Vacinas Virais/uso terapêutico , Animais , Bunyaviridae/patogenicidade , Infecções por Bunyaviridae/prevenção & controle , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Febres Hemorrágicas Virais/prevenção & controle , Humanos , Doenças Raras/prevenção & controle , República da Coreia/epidemiologia , Estudos Retrospectivos , Estudos Soroepidemiológicos , Trombocitopenia/prevenção & controle , Trombocitopenia/virologia , Vacinas Virais/normas
5.
Hematology ; 24(1): 516-520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31242816

RESUMO

Objective: Anemia and thrombocytopenia are the most frequently reported adverse events of ruxolitinib in patients with MPN-associated myelofibrosis (MPN-MF). Although thalidomide, androgens and prednisone have previously demonstrated improvements in myelofibrosis-associated anemia, it is unclear whether these drugs are effective in patients taking ruxolitinib. Method: We conducted a retrospective cohort study to evaluate the efficacy and tolerability of combination therapy with low dose thalidomide, stanozolol and prednisone (TSP) in patients with IPSS intermediate-2 or high-risk myelofibrosis (MF) who received ruxolitinib treatment. Results: Sixty-five patients with MPN-MF who took ruxolitinib were enrolled in this retrospective study, of which 46 patients also took TSP while 19 did not take TSP (TSP and non-TSP groups). Within the first 24 weeks, the proportion of patients with anemia response and platelet count increase ≥50 × 109/L were 45.7% and 67.4% in the TSP group as compared to 0% and 10.5% in the non-TSP group (p < 0.001). The mean hemoglobin level in the non-TSP group reached the nadir after approximately 12-16 weeks of therapy, but gradually increased in the TSP group. Conclusion: In summary, TSP regimen can improve anemia and thrombocytopenia during ruxolitinib treatment in patients with MPN-MF, and the associated adverse events were manageable.


Assuntos
Anemia/induzido quimicamente , Prednisona/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Esplenomegalia/prevenção & controle , Estanozolol/uso terapêutico , Talidomida/uso terapêutico , Trombocitopenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/prevenção & controle , Anemia/terapia , Contagem de Células Sanguíneas , Transfusão de Sangue , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobinas/análise , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Prednisona/administração & dosagem , Mielofibrose Primária/sangue , Mielofibrose Primária/etiologia , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Estudos Retrospectivos , Esplenomegalia/etiologia , Esplenomegalia/patologia , Estanozolol/administração & dosagem , Talidomida/administração & dosagem , Trombocitopenia/sangue , Trombocitopenia/prevenção & controle
6.
Biomarkers ; 24(5): 448-456, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055944

RESUMO

Background: Left ventricular assist devices (LVADs) provide support for patients with end-stage heart failure. The aims of this study were to determine whether baseline analysis and early trends in routine laboratory data, platelet activity, and thromboinflammatory biomarkers following LVAD implantation reveal trends that predict personalized risks of one-year gastrointestinal (GI) bleeding, stroke, pump thrombosis, drive-line infections and mortality in patients on LVAD support. Methods: We performed an observational study at the University of Kentucky with 61 participants who underwent first-time LVAD implantation. Blood was collected at baseline and post-op days 0, 1, 3 and 6 as well as clinical follow-up. Demographics, clinical characteristics, one-year adverse events and routine laboratory data were collected from electronic medical records. Platelet function and plasma biomarkers were profiled. Results: Evaluation of routine laboratory results revealed that sustained thrombocytopenia and increased mean platelet volume (MPV) were associated with development of GI bleeding and mortality. Platelet function at follow-up visit predicted one-year bleeding events. Thrombotic biomarker sCD40L strongly predicted one-year GI bleeding at baseline before implantation and within the first week following LVAD implant. Conclusions: Early trends in routine bloodwork and platelet function may serve as novel signatures of patients at risk to experience adverse events.


Assuntos
Coração Auxiliar/efeitos adversos , Hemorragia , Trombocitopenia , Disfunção Ventricular Esquerda/cirurgia , Adulto , Idoso , Feminino , Insuficiência Cardíaca/cirurgia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Mortalidade , Medicina de Precisão , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle
7.
Thromb Haemost ; 119(7): 1138-1146, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129914

RESUMO

INTRODUCTION/OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) provides circulatory support in patients with severe heart failure, but the frequent use of unfractionated heparin exposes patients to high risk of heparin-induced thrombocytopenia (HIT). We prospectively evaluated the development and clinical impact of platelet factor 4 (PF4)-specific antibodies (Abs) during ECMO and whether specific biological characteristics could predict HIT. MATERIALS AND METHODS: From 2014 to 2018, we studied 57 adults who underwent an ECMO for at least 5 days. The plasma samples collected daily were tested for PF4-specific Abs using immunoassays to detect immunoglobulin (Ig) G, A, and M isotypes or only IgG. Serotonin release assay was performed without and with PF4 to detect pathogenic Abs. RESULTS: Twenty-nine patients (50%) were positive for PF4-specific Abs (IgG, A, M), with IgG in 17/57 (30%) and 16 of them (94%) were immunized within 10 days. PF4-specific IgG Abs did not affect the clinical or biological course of most patients. HIT was suspected in only two patients with ECMO circuit dysfunction and unexpected platelet count decrease after day 5. High levels of PF4-specific IgG were detected in both patients, and HIT was confirmed by a serotonin release assay, which was also more sensitive when exogenous PF4 was present. CONCLUSION: PF4-specific Abs are common during ECMO but are mostly non-pathogenic and not associated with a less favorable prognosis. However, an abnormal platelet count evolution, in particular if associated with ECMO circuit dysfunction, should prompt the search for pathogenic PF4-specific IgG.


Assuntos
Plaquetas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Fator Plaquetário 4/imunologia , Trombocitopenia/prevenção & controle , Adulto , Idoso , Autoanticorpos/sangue , Feminino , França/epidemiologia , Insuficiência Cardíaca/epidemiologia , Heparina/efeitos adversos , Heparina/uso terapêutico , Humanos , Imunidade Humoral , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Serotonina/metabolismo , Trombocitopenia/etiologia , Adulto Jovem
8.
Pediatrics ; 143(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30940676

RESUMO

BACKGROUND AND OBJECTIVES: Thrombocytopenia is associated with late closure of patent ductus arteriosus (PDA). There are few studies evaluating platelet transfusions to treat PDA. We compared liberal platelet-transfusion criteria (to maintain a platelet count >100 000 per µL) versus standard criteria achieve earlier PDA closure among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA (hs-PDA) presenting within the first 2 weeks of life. METHODS: Thrombocytopenic (<100 000 per µL) preterm neonates with hs-PDA were enrolled and randomly allocated to the liberal and standard transfusion groups: 22 in each arm. They underwent echocardiography daily until closure of PDA, completion of 120 hours follow-up, or death. All subjects received standard cotreatment with nonsteroidal antiinflammatory drugs. Primary outcome of time to PDA closure was compared by survival analysis. Multivariate Cox proportional hazard regression was performed with randomization group, baseline platelet count, gestational age, and age at enrollment as predictor variables. RESULTS: Median time to PDA closure was 72 (95% confidence interval [CI] 55.9-88.1) versus 72 (95% CI 45.5-98.4) hours in the liberal versus restrictive transfusion groups, respectively (unadjusted hazard ratio 0.88 [95% CI 0.4-1.9]; P = .697). Despite adjusting for potential confounders, there was no significant difference in time to PDA closure. In the liberal transfusion group, 41% of infants had any grade of intraventricular hemorrhage compared with 4.5% in the restrictive group (P = .009). CONCLUSIONS: Attempting to maintain a platelet count >100 000 per µL by liberally transfusing platelets in preterm thrombocytopenic neonates with hs-PDA does not hasten PDA closure.


Assuntos
Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/terapia , Recém-Nascido Prematuro , Transfusão de Plaquetas/métodos , Trombocitopenia/diagnóstico por imagem , Trombocitopenia/prevenção & controle , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Contagem de Plaquetas/métodos
9.
BMC Pulm Med ; 18(1): 193, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541518

RESUMO

BACKGROUND: Pulmonary carcinosarcoma (PCS) is a rare primary lung malignancy and has a poor prognosis among lung tumor histological subtypes. However, an appropriate treatment strategy has not been developed for unresectable PCS. CASE PRESENTATION: A 65-year-old man who was diagnosed with PCS was treated by surgical removal of the primary lung lesion, followed by six cycles of adjuvant chemotherapy with cisplatin plus irinotecan. Following the chemotherapy, he experienced a relapse with brain metastasis, which induced the rapid onset of left leg paralysis. Radical surgical resection and stereotactic radiosurgery to the resection cavity were performed. However, meningeal dissemination and new lung metastases occurred after a year and half. To control these multiple metastatic lesions, the patient was treated with the multiple kinase inhibitor pazopanib. No change was observed in the meningeal dissemination, while the metastatic lung lesions were prominently reduced in size following treatment with pazopanib. Consequently, the patient showed a partial response to pazopanib treatment, although the dose of pazopanib was reduced by half as a result of thrombocytopenia. CONCLUSION: This is the first report of metastatic PCS showing an evident therapeutic response to tumor-targeted therapy. We suggest that pazopanib may be a therapeutic option for patients with metastatic PCS.


Assuntos
Neoplasias Encefálicas , Carcinossarcoma , Neoplasias Pulmonares , Neoplasias Meníngeas , Pneumonectomia/métodos , Pirimidinas , Sulfonamidas , Trombocitopenia , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinossarcoma/patologia , Carcinossarcoma/fisiopatologia , Carcinossarcoma/terapia , Quimioterapia Adjuvante/métodos , Relação Dose-Resposta a Droga , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Masculino , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Estadiamento de Neoplasias , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Radiocirurgia/métodos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Resultado do Tratamento
10.
J Infect Chemother ; 24(10): 773-781, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30098914

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) caused by SFTS virus (SFTSV), a novel phlebovirus, was reported to be endemic to central and northeastern PR China and was also to be endemic to South Korea and western Japan. SFTS is an emerging viral infection, which should be categorized as a viral hemorrhagic fever disease as Crimean-Congo hemorrhagic fever (CCHF) is caused by CCHF virus. SFTS is a tick-borne viral infection. SFTSV is maintained between several species of ticks and wild and domestic animals in nature. Patients with SFTS show symptoms of fever, general fatigue, and gastrointestinal symptoms such as bloody diarrhea. The severely ill SFTS patients usually show gastrointestinal hemorrhage and deteriorated consciousness. The case fatality rate of SFTS ranges from 5 to 40%. Pathological studies on SFTS have revealed that the mechanisms behind the high case fatality rate are virus infection-related hemophagocytic syndrome associated with cytokine storm, coagulopathy due to disseminated intravascular coagulation causing bleeding tendency, and multi-organ failure. Favipiravir was reported to show efficacy in the prevention and treatment of SFTSV infections in an animal model. A clinical study to evaluate the efficacy of favipiravir in the treatment of SFTS patients has been initiated in Japan. SFTSV is circulating in nature in PR China, Korea, and Japan, indicating that we cannot escape from the risk being infected with SFTSV. The development of specific therapy and preventive measures is a pressing issue requiring resolution to reduce the morbidity and mortality of SFTS patients.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Infecções por Bunyaviridae/tratamento farmacológico , Phlebovirus/patogenicidade , Pirazinas/uso terapêutico , Trombocitopenia/tratamento farmacológico , Idoso de 80 Anos ou mais , Animais , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/patologia , Infecções por Bunyaviridae/prevenção & controle , China/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mortalidade , República da Coreia/epidemiologia , Síndrome , Trombocitopenia/epidemiologia , Trombocitopenia/patologia , Trombocitopenia/prevenção & controle
11.
Oncology (Williston Park) ; 32(7): 339-43, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30080919

RESUMO

Poly(ADP-ribose) polymerase (PARP) proteins are used by cells in several DNA repair processes. PARP inhibition can result in preferential death of cancer cells when another mechanism for repairing DNA is defective. Two PARP inhibitors, olaparib and rucaparib, have been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent, BRCA-associated ovarian cancer. More recently, these two and a third PARP inhibitor, niraparib, were approved by the FDA as maintenance therapy following platinum-based chemotherapy for recurrent ovarian cancer. This has caused a paradigm shift in disease management and a challenge for clinicians, who must decide how best to use these agents in individualized treatment. The oral formulation is attractive to patients, but adverse effects such as nausea and fatigue can impact quality of life. As clinicians become comfortable selecting PARP inhibitors and managing associated toxicities, future steps will be to investigate how to safely administer them in combination with other therapies.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Anemia/induzido quimicamente , Anemia/prevenção & controle , Creatinina/sangue , Esquema de Medicação , Interações de Medicamentos , Exantema/induzido quimicamente , Exantema/prevenção & controle , Fadiga/induzido quimicamente , Fadiga/prevenção & controle , Feminino , Genes BRCA1 , Genes BRCA2 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Indazóis/uso terapêutico , Leucopenia/induzido quimicamente , Leucopenia/prevenção & controle , Mutação , Síndromes Mielodisplásicas/induzido quimicamente , Nasofaringite/induzido quimicamente , Nasofaringite/prevenção & controle , Náusea/induzido quimicamente , Náusea/prevenção & controle , Neoplasias Ovarianas/genética , Piperidinas/uso terapêutico , Pneumonia/induzido quimicamente , Inibidores de Poli(ADP-Ribose) Polimerases/economia , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Transaminases/sangue , Vômito/induzido quimicamente , Vômito/prevenção & controle
12.
Cochrane Database Syst Rev ; 7: CD009447, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29993117

RESUMO

BACKGROUND: The choice of the appropriate perioperative thromboprophylaxis for people with cancer depends on the relative benefits and harms of different anticoagulants. OBJECTIVES: To systematically review the evidence for the relative efficacy and safety of anticoagulants for perioperative thromboprophylaxis in people with cancer. SEARCH METHODS: This update of the systematic review was based on the findings of a comprehensive literature search conducted on 14 June 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL, 2018, Issue 6), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed. SELECTION CRITERIA: Randomized controlled trials (RCTs) that enrolled people with cancer undergoing a surgical intervention and assessed the effects of low-molecular weight heparin (LMWH) to unfractionated heparin (UFH) or to fondaparinux on mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding outcomes, and thrombocytopenia. DATA COLLECTION AND ANALYSIS: Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, PE, symptomatic venous thromboembolism (VTE), asymptomatic DVT, major bleeding, minor bleeding, postphlebitic syndrome, health related quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach (GRADE Handbook). MAIN RESULTS: Of 7670 identified unique citations, we included 20 RCTs with 9771 randomized people with cancer receiving preoperative prophylactic anticoagulation. We identified seven reports for seven new RCTs for this update.The meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with UFH for the following outcomes: mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.63 to 1.07; risk difference (RD) 9 fewer per 1000, 95% CI 19 fewer to 4 more; moderate-certainty evidence), PE (RR 0.49, 95% CI 0.17 to 1.47; RD 3 fewer per 1000, 95% CI 5 fewer to 3 more; moderate-certainty evidence), symptomatic DVT (RR 0.67, 95% CI 0.27 to 1.69; RD 3 fewer per 1000, 95% CI 7 fewer to 7 more; moderate-certainty evidence), asymptomatic DVT (RR 0.86, 95% CI 0.71 to 1.05; RD 11 fewer per 1000, 95% CI 23 fewer to 4 more; low-certainty evidence), major bleeding (RR 1.01, 95% CI 0.69 to 1.48; RD 0 fewer per 1000, 95% CI 10 fewer to 15 more; moderate-certainty evidence), minor bleeding (RR 1.01, 95% CI 0.76 to 1.33; RD 1 more per 1000, 95% CI 34 fewer to 47 more; moderate-certainty evidence), reoperation for bleeding (RR 0.93, 95% CI 0.57 to 1.50; RD 4 fewer per 1000, 95% CI 22 fewer to 26 more; moderate-certainty evidence), intraoperative transfusion (mean difference (MD) -35.36 mL, 95% CI -253.19 to 182.47; low-certainty evidence), postoperative transfusion (MD 190.03 mL, 95% CI -23.65 to 403.72; low-certainty evidence), and thrombocytopenia (RR 3.07, 95% CI 0.32 to 29.33; RD 6 more per 1000, 95% CI 2 fewer to 82 more; moderate-certainty evidence). LMWH was associated with lower incidence of wound hematoma (RR 0.70, 95% CI 0.54 to 0.92; RD 26 fewer per 1000, 95% CI 39 fewer to 7 fewer; moderate-certainty evidence). The meta-analyses found the following additional results: outcomes intraoperative blood loss (MD -6.75 mL, 95% CI -85.49 to 71.99; moderate-certainty evidence); and postoperative drain volume (MD 30.18 mL, 95% CI -36.26 to 96.62; moderate-certainty evidence).In addition, the meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with Fondaparinux for the following outcomes: any VTE (DVT or PE, or both; RR 2.51, 95% CI 0.89 to 7.03; RD 57 more per 1000, 95% CI 4 fewer to 228 more; low-certainty evidence), major bleeding (RR 0.74, 95% CI 0.45 to 1.23; RD 8 fewer per 1000, 95% CI 16 fewer to 7 more; low-certainty evidence), minor bleeding (RR 0.83, 95% CI 0.34 to 2.05; RD 8fewer per 1000, 95% CI 33 fewer to 52 more; low-certainty evidence), thrombocytopenia (RR 0.35, 95% CI 0.04 to 3.30; RD 14 fewer per 1000, 95% CI 20 fewer to 48 more; low-certainty evidence), any PE (RR 3.13, 95% CI 0.13 to 74.64; RD 2 more per 1000, 95% CI 1 fewer to 78 more; low-certainty evidence) and postoperative drain volume (MD -20.00 mL, 95% CI -114.34 to 74.34; low-certainty evidence) AUTHORS' CONCLUSIONS: We found no difference between perioperative thromboprophylaxis with LMWH versus UFH and LMWH compared with fondaparinux in their effects on mortality, thromboembolic outcomes, major bleeding, or minor bleeding in people with cancer. There was a lower incidence of wound hematoma with LMWH compared to UFH.


Assuntos
Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina/administração & dosagem , Neoplasias/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/mortalidade , Complicações Pós-Operatórias/mortalidade , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/prevenção & controle , Trombose/mortalidade , Trombose Venosa/prevenção & controle
13.
Leuk Lymphoma ; 59(12): 2821-2828, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29909708

RESUMO

The aim of this randomized phase II study was to investigate the optimal timing of the administration of thrombopoietin to prevent cytarabine-induced thrombocytopenia. Fifty-two patients who were scheduled for high-dose cytarabine treatment were randomly assigned to receive either the standard prophylactic mode (starting thrombopoietin, 15,000 units/day on days 2-11) or the pre-chemo mode (starting thrombopoietin, 15,000 units/day on days -4, -2, and 2-9) during the first cycle of chemotherapy with a switch to the other mode in the second cycle. The thrombocytopenia rate in the standard mode and the pre-chemo mode were PLT < 50 × 109/L, 67.3% versus 46.2% (p = .001); and PLT < 25 × 109/L, 48.1% versus 26.9% (p = .001). The platelet transfusion rate was reduced in pre-chemo mode, with 7 patients requiring 10 units of platelets, whereas 13 patients required 24 units in standard mode (p = .038). Grade III/IV thrombopoietin-related toxicity was not observed. The prophylactic use of thrombopoietin was effective and safe. Trial registration: ChiCTR-OPB-15007591.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Citarabina/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Trombocitopenia/prevenção & controle , Trombopoetina/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Transfusão de Plaquetas/estatística & dados numéricos , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Adulto Jovem
15.
PLoS One ; 13(5): e0196422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723247

RESUMO

Nectin-2 is a transmembrane glycoprotein which is involved in the process of Ca2+-independent cell-cell adhesion. In our previous study, we have demonstrated that Nectin-2 is over-expressed in breast and ovarian cancer tissues by using gene expression analysis and immunohistochemistry. Furthermore, we discovered multiple anti-Nectin-2 fully human monoclonal antibodies which inhibited tumor growth in in vivo subcutaneous xenograft models with antibody-dependent cellular cytotoxicity (ADCC) as the principal mechanism of action. In this report, we assessed the toxicity of Y-443, a fully human IgG1/kappa anti-Nectin-2 monoclonal antibody exhibiting strong in vitro ADCC and in vivo anti-tumor activity in cynomolgus monkeys (Macaca fascicularis (Cynos)). Unexpectedly, upon administration, Y-443 induced strong thrombocytopenia through Nectin-2 expressed on Cyno platelets, presumably followed by phagocytosis in the mononuclear phagocytic system. To mitigate the adverse safety profile, we mutated the Fc region of Y-443 to reduce the Fc binding activity to Fcγ receptor I, which is the primary receptor for phagocytosis on macrophages. Moreover, we further engineered the Fc through defucosylation to maintain ADCC activity. The resultant Fc engineered antibody, termed Y-634, demonstrated diminished thrombocytopenia in Cyno toxicological studies and maintained anti-tumor activity in a mouse xenograft model. These findings suggest that Y-634 may have a therapeutic potential for the treatment of Nectin-2 positive cancers, and moreover, Fc engineering is a potential mitigation strategy to ameliorate safety liabilities in antibody induced thrombocytopenia while maintaining antibody potency.


Assuntos
Anticorpos Monoclonais/imunologia , Nectinas/antagonistas & inibidores , Nectinas/imunologia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/genética , Citotoxicidade Celular Dependente de Anticorpos , Linhagem Celular Tumoral , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/imunologia , Macaca fascicularis , Masculino , Camundongos , Camundongos SCID , Nectinas/genética , Engenharia de Proteínas , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Vascul Pharmacol ; 106: 54-66, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29510201

RESUMO

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome. METHODS: We applied BPC 157 (10 µg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression. RESULTS: Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged. CONCLUSION: As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.


Assuntos
Fibrinolíticos/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Veia Cava Inferior/cirurgia , Trombose Venosa/prevenção & controle , Animais , Biomarcadores/sangue , Circulação Colateral/efeitos dos fármacos , Modelos Animais de Doenças , Eletrocardiografia , Feminino , Regulação da Expressão Gênica , Hemodinâmica/efeitos dos fármacos , Hemorragia/prevenção & controle , Ligadura , Masculino , Malondialdeído/sangue , Óxido Nítrico/sangue , Flebografia , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Termografia , Trombocitopenia/sangue , Trombocitopenia/prevenção & controle , Fatores de Tempo , Veia Cava Inferior/metabolismo , Veia Cava Inferior/patologia , Veia Cava Inferior/fisiopatologia , Trombose Venosa/sangue , Trombose Venosa/genética , Trombose Venosa/fisiopatologia
17.
Turk Kardiyol Dern Ars ; 46(2): 155-162, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29512619

RESUMO

In cardiology practice, anticoagulation and antiplatelet therapies are essential for most patients. As of yet, there is no high quality evidence regarding these treatments in thrombocytopenic patients, which continues to be an issue. Thrombocytopenia is defined as a platelet count of <150x109/L and is classified as severe when the platelet count is <50x109/L. Pseudothrombocytopenia, drug-induced thrombocytopenia, immune thrombocytopenia, heparin-induced thrombocytopenia, and thrombotic thrombocytopenic purpura are some of the main causes of thrombocytopenia. The current treatment suggestions are conservative, as a result of the lack of evidence, built on defensive treatment strategies and the fear of bleeding complications. Many patients with acute myocardial infarction with thrombocytopenia have undergone percutaneous coronary intervention successfully with adjunctive antiplatelet and anticoagulant use, as has been described in case reports. A risk-benefit ratio should be evaluated for antiplatelet therapy. In the relevant guidelines, while full dose low-molecular-weight heparin (LMWH) is recommended for patients with a thrombocyte count of >50x109/L, a half-dose of LMWH is recommended in patients with thrombocytopenia between 25 and 50x109/L. According to the current guidelines, avoiding antiplatelet and anticoagulant treatment should be restricted to patients with very severe thrombocytopenia (i.e., a platelet count <25x109/L), but new data and recommendations are needed.


Assuntos
Anticoagulantes , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Inibidores da Agregação de Plaquetas , Trombocitopenia , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Guias de Prática Clínica como Assunto , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Trombocitopenia/terapia
18.
Trials ; 19(1): 127, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463280

RESUMO

BACKGROUND: Severe thrombocytopenia should be corrected by prophylactic platelet transfusion prior to central venous catheter (CVC) insertion, according to national and international guidelines. Even though correction is thought to prevent bleeding complications, evidence supporting the routine administration of prophylactic platelets is absent. Furthermore, platelet transfusion bears inherent risk. Since the introduction of ultrasound-guided CVC placement, bleeding complication rates have decreased. The objective of the current trial is, therefore, to demonstrate that omitting prophylactic platelet transfusion prior to CVC placement in severely thrombocytopenic patients is non-inferior compared to prophylactic platelet transfusion. METHODS/DESIGN: The PACER trial is an investigator-initiated, national, multicentre, single-blinded, randomised controlled, non-inferior, two-arm trial in haematologic and/or intensive care patients with a platelet count of between 10 and 50 × 109/L and an indication for CVC placement. Consecutive patients are randomly assigned to either receive 1 unit of platelet concentrate, or receive no prophylactic platelet transfusion prior to CVC insertion. The primary endpoint is WHO grades 2-4 bleeding. Secondary endpoints are any bleeding complication, costs, length of intensive care and hospital stay and transfusion requirements. DISCUSSION: This is the first prospective, randomised controlled trial powered to test the hypothesis of whether omitting forgoing platelet transfusion prior to central venous cannulation leads to an equal occurrence of clinical relevant bleeding complications in critically ill and haematologic patients with thrombocytopenia. TRIAL REGISTRATION: Nederlands Trial Registry, ID: NTR5653 ( http://www.trialregister.nl/trialreg/index.asp ). Registered on 27 January 2016. Currently recruiting. Randomisation commenced on 23 February 2016.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Transfusão de Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/prevenção & controle , Coleta de Dados , Interpretação Estatística de Dados , Hemorragia/prevenção & controle , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Projetos de Pesquisa , Método Simples-Cego
19.
Ann Hematol ; 97(6): 1019-1026, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29464312

RESUMO

Castleman's disease (CD) is a rare lymphoproliferative disorder, and its prevalence in Thailand is not known. This 10-year period study investigated the prevalence of CD in Thailand, and the clinical characteristics and outcomes of Thai CD patients, with special focus on the existence and prevalence of TAFRO syndrome. TAFRO syndrome is defined as CD with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Thirty-three CD patients diagnosed and treated at Siriraj Hospital during January 2007 to December 2016 were included. The prevalence of CD was 1.4 per 1,000,000 patients/10 years. Median age was 46 years, with slight female predominance. Six patients were assigned to the TAFRO group. A high proportion of TAFRO syndrome (18.2%) was found among Thai adult CD patients. In addition to routine TAFRO diagnostic criteria, significantly lower hemoglobin and albumin levels were observed in the TAFRO group than in the non-TAFRO group. Treatment outcomes of CD patients were complete remission (52%), stable disease (30%), and death (13%). Three-year overall survival in the non-TAFRO group and TAFRO group was 88 and 50%, respectively. While most CD patients had a good prognosis, severe cases with TAFRO syndrome had poor outcome.


Assuntos
Hiperplasia do Linfonodo Gigante/fisiopatologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Ascite/etiologia , Ascite/prevenção & controle , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/epidemiologia , Edema/etiologia , Edema/prevenção & controle , Feminino , Febre/etiologia , Febre/prevenção & controle , Seguimentos , Hospitais de Ensino , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Derrame Pleural/prevenção & controle , Prevalência , Prognóstico , Indução de Remissão , Índice de Gravidade de Doença , Análise de Sobrevida , Tailândia/epidemiologia , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle
20.
Leuk Lymphoma ; 59(10): 2377-2382, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29424601

RESUMO

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.


Assuntos
Ácido Aminocaproico/efeitos adversos , Antifibrinolíticos/efeitos adversos , Neoplasias Hematológicas/complicações , Hemorragia/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Tromboembolia/epidemiologia , Adulto , Idoso , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Tromboembolia/induzido quimicamente , Resultado do Tratamento
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