Venous thromboprophylaxis in medical patients: an application review

OBJECTIVE: Routine thromboprophylaxis, despite its well-known effectiveness and the fact that venous thromboembolism is a potentially avoidable condition, is not fully established in clinical practice. The objectives of the present study were to determine how often thromboprophylaxis is used and the presence of thromboembolism risk factors, and to verify the appropriateness of its use in medical inpatients, assuming a long-standing national guideline as a parameter. METHODS: This was a retrospective cross-sectional study, involving inpatients with medical conditions in the adult general ward of a university hospital. The review was based on a defined guideline. RESULTS: 146 patients were included in the review. At least one risk factor for venous thromboembolism was found in 94.5%. In 130 (89%) patients, prophylactic heparin was indicated, and some kind of heparin was prescribed in 73.3%. Regarding the adequacy of prophylaxis, 53.4% of prescriptions were correct regarding prophylaxis indication and dose; 24% had incorrect dose or frequency of use; 19.2% had no prophylaxis prescription, although it was indicated; and in five cases (3.4%), the drugwas prescribed, even though itwas not indicated. CONCLUSION: Thromboprophylaxis is underused in this population, and an inappropriate dose was prescribed in 50% of cases. Therefore, future studies and interventions should include an educational program started from the emergency department care, an essential step to bring evidence closer to clinical practice.OBJETIVO: A tromboprofilaxia de rotina, a despeito de sua efetividade estar bem estabelecida e o tromboembolismo venoso ser uma condição potencialmente evitável, não se apresenta completamente consolidada na prática clínica. Os objetivos do presente estudo são: 1. Determinar a frequência da utilização da tromboprofilaxia e presença dos fatores de risco para tromboembolismo; 2. Verificar a adequação de sua utilização em pacientes clínicos internados, assumindo como parâmetro uma diretriz nacional estabelecida. MÉTODOS: Estudo retrospectivo transversal envolvendo pacientes internados por doenças clínicas em uma enfermaria geral de adultos de um hospital universitário. A análise foi baseada em diretriz definida. RESULTADOS: Foram incluídos 146 pacientes para análise. Destes, 94,5% possuíam pelo menos um fator de risco para tromboembolismo venoso. Em 130 (89%) pacientes havia indicação para uso de heparina profilática, sendo que em 73,3% dos casos estava prescrito algum tipo de heparina. Quanto à adequação da profilaxia, 53,4% das prescrições estavam corretas em relação à indicação e à dose da profilaxia; 24% apresentavam dose ou frequência incorretas; 19,2% não tinham prescrição de profilaxia, apesar de ela ser indicada; e em cinco casos (3,4%) o fármaco foi prescrito, apesar de não haver indicação. CONCLUSÃO: Existe subutilização da tromboprofilaxia nesta população, com inadequada dose prescrita em 50% dos casos. Portanto, estudos e intervenções futuros devem incluir um programa educacional que se inicie desde o atendimento em pronto-socorro, sendo essencial para aproximar a evidência à prática clínica.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Clínica MédicaHospital Sírio-Libanês Centro de Oncologia Departamento de RadioterapiaUniversidade de São Paulo Departamento de Hematologia e HemoterapiaFaculdade de Medicina de Marília Núcleo de Epidemiologia ClínicaFAMEMAUNIFESP, EPM, Depto. de Clínica MédicaSciEL

Population Pharmacokinetic Study of a Test Dose Busulfan Patients Undergoing Hematopoietic Stem Cell Transplantation

UNIFESP (Universidade Federal de São Paulo), BrazilOnco-Hematology Unit, Instituto da Criança - HC - FMUSP, Sao Paulo, BrazilHospital Israelita Albert Einstein, BrazilHematology and Bone Marrow Transplantation Dept, Hospital Israelita Albert Einstein, BrazilHematology and Bone Marrow Transplantation Dept, UNIFESP (Universidade Federal de Sao Paulo), BrazilPediatric Bone Marrow Transplantation Center, Instituto de Oncologia Pediatrica, São Paulo, BrazilHematology and Bone Marrow Transplantation Dept, Hospital Israelita Albert Einstein, Sao Paulo, BrazilInstituto de Oncologia Pediátrica, São Paulo, BrazilClinical Research Center, Instituto de Oncologia Pediátrica, São Paulo, BrazilDepartment of Medicine - Bone Marrow Transplant Program, Case Western Reserve University, ClevelandUNIFESP (Universidade Federal de São Paulo), BrazilHematology and Bone Marrow Transplantation Dept, UNIFESP (Universidade Federal de Sao Paulo), BrazilWeb of Scienc

Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia

Simple Summary In solid tumors, the altered expression of embryonic genes such as the SLIT-ROBO family has been associated with poor prognosis, while little is known about their role in acute myeloid leukemia (AML). Previous studies reported frequent hypermethylation of SLIT2 mediated by the methyltransferase enzyme EZH2 and more recently the PML protein, which are commonly found to be aberrantly expressed in AML. Here, we aim to assess retrospectively the clinical relevance of the SLIT2 gene in acute promyelocytic leukemia, a homogenous subtype of AML. We demonstrated that reduced SLIT2 expression was associated with high leukocyte counts and reduced overall survival in different APL cohorts. STLI2 treatment decreased APL growth, while SLIT2 knockdown accelerated cell cycle progression and proliferation. Finally, reduced expression of SLIT2 in murine APL blasts resulted in fatal leukemia associated with increased leukocyte counts in vivo. These findings demonstrate that SLIT2 can be considered as a prognostic marker in APL, and a potential candidate for clinical studies of a more heterogeneous disease, such as AML. The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2(high) transcript levels were associated with cell cycle arrest, while SLIT2(low) APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p <0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated

Hodgkin's disease and pregnancy: case series and proposal for treatment protocol

The peak frequency of Hodgkin's disease convergesmatches with women of reproductive fertility age. Currently, this disease is the fourth more diagnosed neoplasia during pregnancy. In addition, there is no consensus in the literature on how to treat pregnant women because of the risks of chemotherapy for mothers and for fetuses. We report three cases of pregnant women with Hodgkin's disease. A review of the literature was made aiming to suggest a protocol to treat these patients

Transplante de células-tronco hematopoéticas e leucemia mieloide aguda: diretrizes brasileiras Hematopoietic stem cells transplantation and acute myeloid leukemia: Brazilian guidelines

O objetivo deste trabalho foi definir diretrizes para a indicação do transplante de células-tronco hematopoéticas (TCTH) no tratamento da leucemia mieloide aguda (LMA) no Brasil. O papel do TCTH no tratamento da LMA foi discutido pelosautores e apresentado para a Sociedade Brasileira de Transplante de Medula Óssea na reunião sobre Diretrizes Brasileiras para o TCTH, que o ratificou. Este consenso foi baseado na revisão da literatura internacional e na experiência brasileira em TCTH para o tratamento da LMA. O tratamento ideal para leucemia mieloide aguda em primeira remissão completa (1RC) ainda não está definido. Há consenso na indicação do TCTH alogênico, com condicionamento mieloablativo, para pacientes que apresentem alterações citogenéticas consideradas de alto risco. O TCTH alogênico não está indicado na 1RC para pacientes de baixo risco citogenético e, aparentemente, o TCTH alogênico, autólogo ou a quimioterapia de consolidação são equivalentes para os pacientes de risco intermediário.<br>The objective of this work was to define guidelines for the indication of hematopoietic stem cells transplantation (HSCT) in the treatment of acute myeloid leukemia (AML) in Brazil. The role of HSCT in the treatment of AML was discussed by the authors and presented to the Brazilian Society of Bone Marrow Transplantation in a meeting to formulate and ratify the Brazilian Guidelines on HSCT. This consensus was based on a review of international publications and on the Brazilian experience in HSCT for the treatment of AML. The optimal treatment for AML in first complete remission (1CR) has not been defined yet. There is consensus on the indication of allogeneic HSCT with myeloablative conditioning for patients who present high risk cytogenetic changes. Allogeneic HSCT is not indicated for low cytogenetic risk 1RC patients and, apparently, allogeneic and autologous HSCT and consolidation chemotherapy are similar for intermediate risk patients