Idiosyncratic Drug-Induced Agranulocytosis: The Paradigm of Deferiprone

Pontikoglou, Charalampos; Papadaki, Helen Α.

doi:10.3109/03630269.2010.484791

Cited by 30 publications

(17 citation statements)

References 45 publications

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“…Immunomodulatory effects of clozapine were reported previously regarding in vivo cytokine synthesis and release [20]. The immunosuppressive effect observed in our study may be related to a nonspecific cytotoxic effect of this agent [20,21]. However, none of our patients developed agranulocytosis during the clozapine treatment, thus the relationship between the suppression of immunocompetent cells and the reduction in PAA levels remains speculative.…”

Section: Discussioncontrasting

confidence: 43%

Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study

Ebert¹,

Schechtman

Midbari

et al. 2015

Neuropsychobiology

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Background: Previous studies have demonstrated significantly higher blood titers of platelet-associated autoantibodies (PAA) in adult schizophrenia patients compared to normal healthy subjects. In addition, young adult schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder. Aim: To assess longitudinally the blood titers of PAA in inpatients with childhood-onset schizophrenia at admission, after short- and long-term follow-up, and the correlation of these titers with the response to clozapine and other antipsychotic treatments. Methods: Thirty children, age range of 6-12 (mean ± SD: 9.6 ± 1.5 years), with DSM-IV TR schizophrenia in active psychotic state were assessed 3 times: at baseline, after short-term (8-17 weeks; n = 26) and after long-term follow-up (33-170 weeks; n = 19). The blood titers of PAA were analyzed using ELISA and expressed by a linear optical density (OD) scale. A test recording >1.4 OD units was predefined as the positive cutoff value. Results: On long-term follow-up, 9 out of the 17 children who were PAA-positive at baseline became PAA-negative: 7 already after 2 months of clozapine treatment and 2 following 3 years of risperidone treatment. Eight children remained PAA-positive during the entire study period. There was no significant correlation between the clinical improvement (as assessed by change in the Positive and Negative Syndrome Scale score) and the alteration in PAA levels (n = 19, r = -0.4, p = 0.088). Conclusions: High rates of positive PAA in COS patients may indicate an active autoimmune process in early-onset schizophrenia. It is concluded that PAA may serve as a biomarker for the diagnosis of COS, but does not predict the response to treatment. A transition to a PAA-negative status does not indicate an improvement in psychosis.

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Section: Discussioncontrasting

confidence: 43%

Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study

Ebert¹,

Schechtman

Midbari

et al. 2015

Neuropsychobiology

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“…With almost all drugs in common usage that can give rise to neutropenia/agranulocytosis the risk is considered acceptable, even with chemotherapeutic agents, given the benefits derived from continued availability of the drug and that the timely withdrawal of the offending agent, if appropriate, is usually successful in preventing a fatal outcome (Andersohn et al ., 2007). High‐risk non‐chemotherapeutic drugs include anti‐thyroid drugs, clozapine, ticlopidine, sulfasalazine, dipyrone, trimethoprim/sulfamethoxazole, carbamazepine, deferiprone (L1) and probably rituximab (Garbe, 2007; Pontikoglou and Papadaki, 2010). There may of course be risks from hitherto unsuspected sources such as the use of illicit cocaine adulterated with levamisole, which may have confused putative identification of offending agents in recent years (Buchanan et al ., 2010).…”

Section: Introductionmentioning

confidence: 99%

Haematological toxicity of clozapine and some other drugs used in psychiatry

Nooijen

Carvalho

Flanagan

2011

Hum. Psychopharmacol. Clin. Exp.

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There remain several difficult areas, including the criteria for clozapine rechallenge. Experience has emphasised (i) the role of appropriate timing of WCC sample collection to ensure that clozapine is not withdrawn unnecessarily and (ii) the success of agents such as filgrastim in promoting rapid production of granulocytes if the situation so demands. On the other hand, the use of lithium to promote a leucocytosis has taken hold without a clear risk: benefit analysis. Be this as it may, should patients decide that they no longer wish to undergo WCC monitoring after 12 months on clozapine, cessation of monitoring is probably preferable to stopping the drug since overall mortality is decreased in patients treated with clozapine.

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“…This could have decreased the bone marrow's exposure to the drug. Although the case fatality of agranulocytosis has recently been decreased to 5% (12), the lower risk of agranulocytosis during alternating sequential therapy deserves consideration. Compliance was higher for L1 treatment in both arms of the trial than for DFO treatment in the alternating sequential treatment.…”

Section: Discussionmentioning

confidence: 99%

Sequential Alternating Deferiprone And Deferoxamine Treatment Compared To Deferiprone Monotherapy: Main Findings And Clinical Follow-Up Of A Large Multicenter Randomized Clinical Trial In -Thalassemia Major Patients

et al. 2011

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In β-thalassemia major (β-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO vs. L1 alone iron chelation therapy in β-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during a 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin level was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients (p = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences (log-rank test, p = 0.3145). Adverse events and costs were comparable between the groups. Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone, without significant differences of survival, adverse events or costs. These findings were confirmed in a further 21-month follow-up. These data suggest that alternating sequential L1-DFO treatment may be useful for some β-TM patients who may not be able to receive other forms of chelation treatment.

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Idiosyncratic Drug-Induced Agranulocytosis: The Paradigm of Deferiprone

Cited by 30 publications

References 45 publications

Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study

Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study

Haematological toxicity of clozapine and some other drugs used in psychiatry

Sequential Alternating Deferiprone And Deferoxamine Treatment Compared To Deferiprone Monotherapy: Main Findings And Clinical Follow-Up Of A Large Multicenter Randomized Clinical Trial In -Thalassemia Major Patients

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