ABSTRACT
INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.
Subject(s)
Anemia, Sickle Cell/complications , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Thrombophilia/drug therapy , Thrombophilia/etiology , Ticagrelor/therapeutic use , Anemia, Sickle Cell/blood , Blood Coagulation/drug effects , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Drug Monitoring , Humans , Molecular Structure , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Purinergic P2Y Receptor Antagonists/chemistry , Purinergic P2Y Receptor Antagonists/pharmacology , Thrombophilia/prevention & control , Ticagrelor/chemistry , Ticagrelor/pharmacokinetics , Treatment OutcomeABSTRACT
OBJECTIVE: This study investigated the co-existence of Leishmania chagasi infection and childhood leukemia in patients naïve to treatment; this has serious clinical and epidemiological implications. METHODS: The seroprevalence of L. chagasi antibodies prior to any treatment was investigated in children with clinical features of acute leukemia. Serological tests were performed in 470 samples drawn from under 14-year-old children from different regions of Brazil with clinical suspicion of acute leukemia. Acute leukemia subtypes were characterized by immunophenotyping using flow cytometry. Morphological analyses of bone marrow aspirates were systematically performed to visualize blast cells and/or the formation of L. chagasi amastigotes. Data analysis used a standard univariate procedure and the Pearson's chi-square test. RESULTS: The plasma of 437 children (93%) displayed antibodies against L. chagasi by indirect immunofluorescence assay and enzyme-linked immunosorbent assay tests. Of the 437 patients diagnosed from 2002 to 2006, 254 had acute lymphoblastic leukemia, 92 had acute myeloid leukemia, and 91 did not have acute leukemia. The seroprevalence of L. chagasi antibodies according to the indirect immunofluorescence assay test (22.5%) was similar in children with or without acute leukemia (p-value=0.76). The co-existence of visceral leishmanasis and acute leukemia was confirmed in 24 children. The overall survival of these children was poor with a high death rate during the first year of leukemia treatment. CONCLUSION: In the differential diagnosis of childhood leukemia, visceral leishmanasis should be considered as a potential concurrent disease in regions where L. chagasi is endemic.
ABSTRACT
Objective: This study investigated the co-existence of Leishmania chagasi infection and childhood leukemia in patients naïve to treatment; this has serious clinical and epidemiological implications. Methods: The seroprevalence of L. chagasi antibodies prior to any treatment was investigated in children with clinical features of acute leukemia. Serological tests were performed in 470 samples drawn from under 14-year-old children from different regions of Brazil with clinical suspicion of acute leukemia. Acute leukemia subtypes were characterized by immunophenotyping using flow cytometry. Morphological analyses of bone marrow aspirates were systematically performed to visualize blast cells and/or the formation of L. chagasi amastigotes. Data analysis used a standard univariate procedure and the Pearson's chi-square test. Results: The plasma of 437 children (93%) displayed antibodies against L. chagasi by indirect immunofluorescence assay and enzyme-linked immunosorbent assay tests. Of the 437 patients diagnosed from 2002 to 2006, 254 had acute lymphoblastic leukemia, 92 had acute myeloid leukemia, and 91 did not have acute leukemia. The seroprevalence of L. chagasi antibodies according to the indirect immunofluorescence assay test (22.5%) was similar in children with or without acute leukemia (p-value = 0.76). The co-existence of visceral leishmanasis and acute leukemia was confirmed in 24 children. The overall survival of these children was poor with a high death rate during the first year of leukemia treatment. Conclusion: In the differential diagnosis of childhood leukemia, visceral leishmanasis should be considered as a potential concurrent disease in regions where L. chagasi is endemic...
