Aplastic Anemia and Severe Myelosuppression with Boceprevir or Simeprevir-Containing Hepatitis C Virus Treatment

ABSTRACT The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.

Rash y anemia aplásica inducidos por fenitoína: caso clínico / Phenytoin-induced rash and aplastic anemia: case report

Rash is a common side effect associated with antiepileptic drugs. The rate of a phenytoin rash is 5.9 percent and increases to 25 percent in those with another antiepileptic drug rash. Aplastic anemia is an adquired hematopoietic stem-cell disorder characterized by pancytopenia of the peripheral blood and hypocellular bone marrow. The use of phenytoin is associated with a 3.5 fold increased risk of aplastic anemia. We report a case of a 70-year-old woman who developed two severe adverse reactions simultaneously with phenytoin: a maculopapular pruritic rash with involvement of mucous and an aplastic anemia. Both conditions normalized after phenytoin withdrawal.

El rash es un efecto secundario común asociado al uso de fármacos antiepilépticos. La frecuencia de rash con fenitoína se ha estimado en un 5,9 por ciento y asciende a un 25 por ciento en pacientes que han presentado rash con otro fármaco antiepiléptico. La anemia aplásica es una anomalía adquirida de las células madre hematopoyéticas caracterizada por pancitopenia de la sangre periférica y médula ósea hipocelular. Los pacientes tratados con fenitoína presentan un riesgo 3,5 veces mayor de desarrollar anemia aplásica. Presentamos el caso de una mujer de 70 años que desarrolló dos reacciones adversas severas y simultáneas a la fenitoína: un exantema maculopapular pruriginoso con compromiso de mucosas y una anemia aplásica. Ambas condiciones se resolvieron completamente con la suspensión del fármaco.

Neutropenia, agranulocytosis and dipyrone

CONTEXTO: Neutropenia e agranulocitose podem ser definidas como contagem de granulócitos inferior a 1.500/mm3 e 500/mm3, respectivamente. Agranulocitose é uma doença séria e rara, freqüentemente causada por medicações. A letalidade é de aproximadamente 10%. As manifestações clínicas mais comuns são infecções como tonsilite, faringite, estomatite e pneumonia. A dipirona é uma das medicações sabidamente associadas a agranulocitose. Entretanto, a intensidade desta associação tem sido motivo de muita controvérsia. Adicionalmente, analgésicos e antipiréticos alternativos não são livres de efeitos adversos graves. CONCLUSÕES: Desta forma, é necessário estabelecer a incidência da agranulocitose na América Latina e o papel da dipirona. Com o objetivo de responder estas questões, está em andamento o LATIN, um estudo caso-controle, multicêntrico, internacional.

Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria following aplastic anaemia.

A young lady who had aplastic anaemia presented for cerebral venous thrombosis after five years of follow up. She was diagnosed to have paroxysmal nocturnal haemoglobinuria. She had received immunosuppressive therapy with methylprednisolone, cyclosporine-A, anti-lymphocyte globulin, danazol and pregnenolone. The relation between aplastic anaemia, paroxysmal nocturnal haemoglobinuria and cerebral venous thrombosis is discussed. The role of immunosuppressive therapy for aplastic anaemia in causation of paroxysmal nocturnal haemoglobinuria is reviewed.

Metamizol: evaluación del riesgo para agranulocitos y anemia aplástica / Metamizol: assessment for agranulocitos and aplastic anemia risk. Three-year experience at Hospital Regional de Mérida, ISSSTE

Antecedentes: el metamizol es un fármaco con amplio uso como analgésico en los hospitales del sector salud con alrededor de 24,000 prescripciones/paciente por año (82,806 prescripciones den tres años). Objetivos. conocer la frecuencia de la agranulocitosis y de la anemia aplásica en los sujetos derechohabientes del Hospital Regional Mérida, del ISSSTE, y buscar la relación con la ingestión de metamizol. Material y métodos: Se revisaron los registros del servicio de hematología del Hospital Regional Mérida desde 1992. También se revisaron los registros de 10 años previos del servicio de medicina interna (ingresos por agranulocitosis o anemia aplástica), así como los registros del consumo de medicamentos y de metamizol del hospital mediante los registros de la farmacia de tres años a la fecha. Resultados: se encontraron tres años de investigación retrospectiva ninguno de ellos se asoció al uso del metamizol Conclusiones: el metamizol o dipirona se puede considerar un fármaco de primera línea para el tratamiento de padecimientos que cursan con dolor, con un poco o ningún efecto adverso del tipo de las discrasias sanguíneas

Cinco episodios de anemia aplástica transitoria en tres enfermos / Five episodes of transiet aplastic anemia in three patients

Se informan cinco episodios de anemia aplástica (AA) grave en tres enfermos, dos mujeres y un varón, de 32, 56 y 41 años de edad, respectivamente, el último con tres episodios. Fueron relacionados con exposición a insecticidas, solventes y fármacos (trimetoprim con sulfametoxazol, pirimetamina y derivados de pirazolanas). Acudieron con padecimintos de dos semanas de evolución con anemia, púrpura mucocutánea y en tres episodios fiebre. Como tratamiento en tres casos se utilizó prednisona y danazol por 10 días, así como antibióticos. En todos los casos se observó recuperación espontánea al cabo de 16 a 45 días que no se correlacionó con infección viral, hemoglobinopatía o evidencia de proceso mieloproliferativo. Se diagnósticaron como AA transitoria, variante de la AA con recuperación temprana y completa de la hematopoyesis

Surveillance of drug induced diseases in children.

A hospital based prospective study on drug induced diseases (DID) in children below 14 years of age was done for a duration of two years. A total number of 20,310 patients were examined in pediatric department during this period, out of which 204 (1.004%) patients were diagnosed as DID. Children with severe reactions were admitted in pediatric ward for in hospital intensive surveillance. The male:female ratio in DID was 1.2:1. DID were most common in neonates (24.51%). Erythmatous maculopapular rashes (67.12%) formed the most common pool of DID in neonates. Thrombophlebitis (41.56%) was most commonly seen in infants above 28 days of life, and in children up to 14 years of age. Out of 204 cases of DID, 9 (4.41%) died. Aplastic anemia was most morbid DID, as all the 7 patients of aplastic anemia died. Chloramphenicol was responsible for all the cases of aplastic anemia. Other two deaths were from erythma multiforme and C.C.F. The most commonly involved drugs, other substances and vaccines were baby powders, massage oils, ampicillin, co-trimoxazole, i.v. infusions (electrolytes and mannitol), DPT and measles vaccines.

Acquired aplastic anemia in children: a review of 100 patients.

A retrospective study of acquired aplastic anemia in 100 Thai children treated with testosterone and prednisolone during 1969 to 1987 is reported. The age ranged from 3-14.5 years (mean 10.3 years). The male to female ratio was 2.3:1. The duration of follow up ranged from 1-17 year (mean 5 years). Prior exposure to possible etiologic agents was found in 36% : antipyretics, Ya-chood, insecticides, benzene, chloramphenicol and paint. The presenting symptoms were bleeding and anemia 72%, fever with either bleeding or anemia 28%. The common sites of bleeding were purpura, epistaxis, gum and teeth, and the gastrointestinal tract. All patients received appropriate supportive treatment and testosterone combined with prednisolone. The results of treatment were evaluated in 80 cases who were followed up until death or at least one year after the diagnosis. Two-thirds of the patients presented with laboratory findings similar to severe aplastic anemia; the fatality rate was 50% (40/80). Most of them succumbed to infection or bleeding in the first 6 months after diagnosis. The recovery rate was 50% with complete, partial and initial responses in 28%, 17% and 5% respectively. The late malignancy rate was 2%. For severe aplastic anemia or for patients who have poor prognostic factors, early approaches of bone marrow transplantation or antilymphocyte globulin administration should be considered.

Uma análise crítica sobre benefícios e riscos da dipirona / A critical analysis on benefits and risks of dipyrone

Os Analgésicos-Antipiréticos säo drogas maciçamente consumidas a nível mundial e, por serem fármacos relativamente antigos, pouco se tem publicado a esse respeito. Este estudo visa fazer uma análise crítica e objetiva sobre os riscos e benefícios na utilizaçäo de analgésicos, bem como sobre a coerência de alternativas terapêuticas. Foi examinada extensa e profunda análise da literatura científica internacional sobre o assunto, com particular atençäo ao notável Estudo de Boston. Conclui-se que o uso de analgésicos é bastante seguro, sendo que a dipirona é o fármaco mais bem avaliado quanto ao seu perfil de segurança

[Acquired aplastic anaemia. Report of 10 cases]

In Averroes Hospital, ten cases of acquired aplastic anaemia have been diagnosed in patients coming from Casablanca. This frequency sets an etiologic problem and a toxic cause is looked upon, especially the chloramphenicol which is greatly used in Morocco. The dark Prognosis of the disease imposes a great care when using this product