On the third day of symptoms, his CBC showed an Hct of 45%, a WBC count of 6100 (ANC of 3170) and a plt count of 211,000, and a rapid dengue test (IgM) came back positive. His antipsychotic continued to be offered as usual, that is, CLZ 300 mg per day. He presented progressive improvement of physical symptoms during the next 4 days. No clinical or laboratory test abnormalities

were noticed at his discharge from day hospital 2 months later, at which time there had been a satisfactory psychopathological improvement. Discussion Despite mild leucopenia usually found among patients with dengue, severe cases are not often observed, with only one previous Inhibitors,research,lifescience,medical TAK-875 molecular weight reported case of agranulocytosis due to dengue infection [Insiripong, 2010]. The hematological alterations in dengue infection are probably the result of bone marrow suppression with a minor contribution of blood cell destruction by the hemophagocytosis in peripheral blood. This bone marrow suppression probably results Inhibitors,research,lifescience,medical from Inhibitors,research,lifescience,medical direct infection of hemopoietic progenitor and bone marrow stroma cells; these latter cells cause release of hematodepressive cytokines, which contribute to the downregulation of hematopoiesis, acting as a

protective mechanism limiting injury to bone marrow during infection [La Russa and Innis, 1995; Srichaikul and Nimmannitya, 2000]. It is postulated that the activation of metabolites of CLZ to electrophilic nitrenium ions may cause idiosyncratic

neutropenia/agranulocytosis Inhibitors,research,lifescience,medical events through direct binding of these ions to neutrophils, causing cell death by oxidative stress-induced apoptosis, and finally by directly targeting the bone marrow stroma cells [Pirmohamed and Park, 1997; Husain et al. 2006; Pereira and Dean, 2006; Flanagan and Dunk, 2008]. However, the precise mechanisms of CLZ-induced leucopenia/agranulocytosis Inhibitors,research,lifescience,medical are still unclear [Guest et al. 1998; Coleman, 2001; Rajagopal, 2005]. Nevertheless, it is well recognized that the overlap of risk factors for blood dyscrasias may increase their occurrence (e.g. concomitant use of carbamazepine and CLZ, two drugs recognized to induce neutropenia). Patients on CLZ treatment are often Adenosine on this drug as the last therapeutic option, providing them with a pharmacological lifeline. Any reason to discontinue CLZ treatment must be judged very carefully. What should be considered when analyzing our reported cases, therefore, is the probable increased likelihood of blood dyscrasias among CLZ-treated patients during dengue infection, due to the occurrence of an overlap of risk for developing neutropenia. It seems plausible that the main cause of dyscrasias in these patients is the dengue infection, considering the benign characteristics of the events, with rapid normalization of CBC and tolerance to CLZ rechallenge.