Clozapine induced blood dyscrasias and a therapeutical approach

2016 ◽  
Vol 33 (S1) ◽  
pp. S613-S613
Author(s):  
A. Gomez Peinado ◽  
P. Cano Ruiz ◽  
S. Cañas Fraile ◽  
M. Gonzalez Cano ◽  
G.E. Barba Fajardo
Keyword(s):  
Mental Health ◽  
Side Effects ◽  
Blood Count ◽  
Complete Blood Count ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Simultaneous Treatment ◽  
Clozapine Treatment ◽  
Competing Interest ◽  
Stimulating Factor

IntroductionClozapine is a neuroleptic commonly used in treatments resistant to schizophrenia. However, despite the benefits, clozapine might cause some serious side effects. Hence, it is of the utmost necessity to keep an exacting control of the patients.ObjectivesTo study some of the therapeutical approaches to the treatment of clozapine induced neutropenia and agranulocytosis.MethodsReview of some articles in Mental Health Journals.ResultsThe treatment with clozapine, substratum of aminergic and muscarinic receptors, entails a 0.9% risk of causing agranulocytosis, and approximately a 2.7% risk of causing neutropenia. Both occur, over 80% of them, during the first 18 weeks of treatment. Thus, before starting it, it is necessary to draw some blood and analyze the complete blood count (CBC). Also, we must analyze CBCs weekly during the first 18 weeks. Other dyscrasias like leukopenia, leukocytosis, anaemia, eoshinophilia, thrombocythaemia or thrombocytopenia can also be observed. When agranulocytosis appears, it can be treated by discontinuing the clozapine treatment, but also using granulocyte-colony stimulating factor or lithium, both separated or combined with clozapine. Lithium produces reversible leukocytosis onceplasma levels of > 0.4 mmol/L are reached. Despite the simultaneous treatment with lithium, clozapine can trigger some neurological side effects, it seems that seizure risk remains invariable.ConclusionsSome of the clozapine's side effects, like neutropenia or agranulocytosis, are potentially lethal. Their treatment consists of discontinuing clozapine or initiating granulocyte-colony stimulating factor or lithium. These are good options that can give rise to a later continued treatment with clozapine.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Recovery from Cyclophosphamide Overdose in a Dog

2017 ◽  
Vol 53 (4) ◽  
pp. 230-235 ◽  
Author(s):  
Jessica Renee Finlay ◽  
Kenneth Wyatt ◽  
Courtney North
Keyword(s):  
Blood Count ◽  
Complete Blood Count ◽  
Hemorrhagic Cystitis ◽  
Complete Recovery ◽  
Oral Cyclophosphamide ◽  
Granulocyte Colony Stimulating Factor ◽  
Heart Murmur ◽  
Stimulating Factor ◽  
Peripheral Neutrophil

ABSTRACT An adult female spayed dog was evaluated after inadvertently receiving a total dose of 1,750 mg oral cyclophosphamide, equivalent to 2,303 mg/m2, over 21 days (days −21 to 0). Nine days after the last dose of cyclophosphamide (day +9), the dog was evaluated at Perth Veterinary Specialists. Physical examination revealed mucosal pallor, a grade 2/6 systolic heart murmur, and severe hemorrhagic cystitis. Severe nonregenerative pancytopenia was detected on hematology. Broad spectrum antibiotics, two fresh whole blood transfusions, granulocyte colony stimulating factor, and tranexamic acid were administered. Five days after presentation (day +14), the peripheral neutrophil count had recovered, and by 12 days (day +21) the complete blood count was near normal. A second episode of thrombocytopenia (day +51) was managed with vincristine, prednisolone, and melatonin. The dog made a complete recovery with no long-term complications at the time of writing. To the author's knowledge, this is the highest inadvertently administered dose of cyclophosphamide to result in complete recovery.

scholarly journals S1. CLOZAPINE RECHALLENGE FOLLOWING NEUTROPENIA USING GRANULOCYTE COLONY-STIMULATING FACTOR: A QUEBEC CASE SERIES

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Laurent Béchard ◽  
Olivier Corbeil ◽  
Maude Plante ◽  
Marc-André Thivierge ◽  
Charles-Émile Lafrenière ◽  
...  
Keyword(s):  
Neutrophil Count ◽  
Demographic Data ◽  
Case Series ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Resistant ◽  
Previous Response ◽  
Response Level ◽  
Clozapine Treatment ◽  
Stimulating Factor

Abstract Background Clozapine possesses unique efficacy profile in treatment-resistant schizophrenia but is associated with neutropenia and agranulocytosis, in respectively, 3% and 0.7% of exposed patients. Granulocyte colony-stimulating factor (G-CSF) has been used to allow clozapine continuation or rechallenge in such situation (1,2). Methods We aim to describe the use of G-CSF to maintain clozapine despite neutropenia or agranulocytosis in treatment resistant schizophrenia patients in Quebec province, Canada. A national clozapine hematological monitoring database was consulted to identify all patients who have had red event (neutrophil count < 1,5 threshold) since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who have received at least one dose of G-CSF while been exposed to clozapine All patients with an active cancer diagnosis while taking clozapine and G-CSF were excluded. A group of pharmacists specialized in psychiatry in Quebec was also contacted to ensure selecting all cases in the province. In additional to demographic data and clozapine and G-CSF details, Clinical Global Impression severity scale (CGI-S) was used to evaluate psychopathology severity during four critical turning points: before and after clozapine introduction, after agranulocytosis episode and after clozapine rechallenge. All data were collected retrospectively, using patient’s medical files, from January to July 2019. Results Eight (8) patients (5 males, 3 females), Caucasian, mean age 48 years old, with clozapine median exposition of 4.8 years, were identified. In 7/8 of those, G-CSF was used according to an “as required strategy”, i.e., whenever the patient’s neutrophil count dropped below a pre-determined threshold, varying according to patient between 0,8 à 1,5. In the other patient, a 3-weekly doses were preventively administered. Despite this, a mean number of 4 red events (ranging from 1 to 10 events) were subsequently observed in those patients, leading to clozapine cessation in 4/8 patients. One other patient responded to G-CSF but the clinical team felt uncomfortable to maintain clozapine in such circumstances. No complication (infection for instance) due to low neutrophil counts was observed nor any significant side effect related to G-CSF. However, in all these cases, while clozapine treatment was associated with clinically significant improvement of psychopathology (mean CGI-S decreased from 5.5 to 3.4), clozapine cessation led to an important psychotic deterioration (mean CGI-S of 6.2) at follow up. Fortunately, in patients successfully rechallenged (3/8), a strong clinical improvement was observed, with return to previous response level observed. Discussion To our knowledge, this is the largest case series of clozapine rechallenge using G-CSF and adds to the 39 already described cases in which G-CSF was concomitantly used with clozapine (1,2). While an “as required” strategy was mainly used here, a different prophylactic G-CSF use may have led to higher rates of clozapine maintenance, despite red codes, which provides the impetus for further studies. Reference

Outcomes of CAG Regimen for Refractory Biphenotypic Acute Leukemia Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4111-4111
Author(s):  
Guangsheng He ◽  
Xiang Zhang ◽  
Wu Depei ◽  
Aining Sun ◽  
Zhengming Jin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Cytosine Arabinoside ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Bone Marrow Depression ◽  
Chemotherapy Toxicity ◽  
Lymphoid Lineage ◽  
Stimulating Factor ◽  
Biphenotypic Acute Leukemia

Abstract Abstract 4111 Objective Biphenotypic acute leukemia (BAL) involves both myeloid and lymphoid cells, and there is lack of uniformity in treatment at present. Optimal approach for therapy of BAL is unknown, and BAL usually becomes refractory to conventional chemotherapy. It was found that CAG regimen [low-dose cytosine arabinoside (Ara-C) plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor (G-CSF)] is effective for both myeloid leukemia and refractory acute lymphoblastic leukemia. To explore the efficiency of CAG regimen for refractory BAL, 12 BAL patients who were failed to daunorubicin/mitoxantrone, cytosine arabinoside, vincristine, prednisone (D/MAOP) regimen, were treated by CAG. 8 were males and 4 was female, with ages ranging from 20 to 43 years (median=34 years). Immunophenotype of B lymphoid lineage/myeloid lineage showed in 8 patients, and T lymphoid lineage/myeloid lineage showed in 4 patients. The patients whose blast cells did not decrease 50% after induction regimen with lymphoid and/or myeloid drugs were defined as refractory cases. Methods 12 refractory BAL patients were treated by CAG regimen (cytosine arabinoside 10 mg/m2 subcutaneously every 12 hours, day 1-14; aclarubicin 5-7 mg/m2 intravenously daily, day 1-8; and concurrent use of granulocyte colony-stimulating factor 200μg·m-2·d-1 subcutaneously) from November 2002 to April 2009. The efficacy of the regimen was evaluated by response rate, and the side-effects was also measured. Results The major chemotherapy toxicity was bone marrow depression, mainly showing as pancytopenia. Median duration of absolute neutrophil count (ANC)<0.50×109/L and of platelet (PLT) count<20×109/L was 13 (range, 1-17) days and 1 day (range, 0-5 days), respectively. Median transfusion of red cells and PLT was 4 (range, 1.5-12) U and 20 (range, 0-40) U, respectively. Besides bone marrow depression, other side-effects such as infection, bleeding, nausea and vomiting also occurred during therapy. According to chemotherapy toxicity assessment of WHO, there were 7 patients confronting infection, among whom only 2 patient occurred III-‡W infection. No serious nausea vomiting or hepatic function damage happened. Disclosures: No relevant conflicts of interest to declare.

Allometric Dose Retranslation Unveiled Substantial Immunological Side Effects of Granulocyte Colony–Stimulating Factor After Stroke

Stroke ◽  
2014 ◽  
Vol 45 (2) ◽  
pp. 623-626 ◽  
Author(s):  
Daniel-Christoph Wagner ◽  
Claudia Pösel ◽  
Isabell Schulz ◽  
Gerda Schicht ◽  
Johannes Boltze ◽  
...  
Keyword(s):  
Side Effects ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

scholarly journals Agranulocytosis Induced by Tamoxifen in a Breast Cancer Patient

Breast Care ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 72-74 ◽  
Author(s):  
Hugo Herrscher ◽  
Julie Leblanc ◽  
Thierry Petit
Keyword(s):  
Breast Cancer ◽  
Adverse Event ◽  
Side Effects ◽  
Tamoxifen Treatment ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Adjuvant Setting ◽  
Case Presentation ◽  
Hematologic Disorder ◽  
Stimulating Factor

Background: The main side effects of tamoxifen are menopausal symptoms. We report a case of agranulocytosis induced by tamoxifen in a 33-year-old woman treated in the adjuvant setting. Case Presentation: Ten days after the beginning of tamoxifen treatment, the patient complained of asthenia and mucositis. Blood testing showed a grade 4 neutropenia (0.06 G/L) without any other major hematologic disorder. Tamoxifen was discontinued, and the patient received granulocyte colony-stimulating factor. Within 2 days, she recovered to a normal granulocyte count. Tamoxifen was then switched to the combination of ovarian suppression (triptorelin) and aromatase inhibitor (anastrozole). Conclusion: Agranulocytosis is a very rare adverse event of tamoxifen.

scholarly journals Simultaneous treatment with carbimazole and granulocyte-colony stimulating factor in a patient with thyrotoxicosis and carbimazole induced neutropenia

Open Medicine ◽  
2006 ◽  
Vol 1 (4) ◽  
pp. 419-423
Author(s):  
Indrajit Talapatra ◽  
Vengal Nagareddy ◽  
Manju Bhavnani ◽  
David Tymms
Keyword(s):  
White Cell Count ◽  
Subtotal Thyroidectomy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Simultaneous Treatment ◽  
Levothyroxine Replacement ◽  
Iodine Treatment ◽  
To Receive ◽  
Stimulating Factor

AbstractWe describe a patient who was admitted with uncontrolled thyrotoxicosis and carbimazole induced neutropenia. She required 80 mg of carbimazole daily. The patient declined radio-iodine treatment because she had a little child and wished to have thyroid surgery. She received four doses of filgrastim (Granulocyte-colony stimulating factor) which maintained the neutrophil count within a reasonable level while she continued to receive carbimazole to prepare her for surgery. After a curative subtotal thyroidectomy and discontinuation of the carbimazole, the patient’s white cell count remained normal. Subsequently the patient was euthyroid on levothyroxine replacement. Carbimazole should always be discontinued if neutropenia occurs but this case demonstrates that in exceptional circumstances filgrastim can be an effective therapy while continuing carbimazole in the short term.

162 Add-on Filgrastim During Clozapine Rechallenge Unsuccessful in Treating Benign Ethnic Neutropenia

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 98-99 ◽  
Author(s):  
Molly Britton ◽  
Palanikumar Gunasekar ◽  
Vithyalakshmi Selvaraj
Keyword(s):  
Suicidal Behavior ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Middle Eastern ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Resistant ◽  
Clozapine Treatment ◽  
Stimulating Factor ◽  
Funding Acknowledgements

AbstractClozapine is an atypical antipsychotic approved by the Food and Drug Administration for treatment-resistant schizophrenia and also indicated for the reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. The most serious side effect of clozapine treatment is agranulocytosis, which is defined as an absolute neutrophil count (ANC) < 0.50 × 109 per L. Benign ethnic neutropenia (BEN) is a condition found in members of African or Middle Eastern descent that is characterized by ANC < 1.50 × 109 per L in the absence of other causes. Filgrastim is a granulocyte colony-stimulating factor (G-CSF) that has shown efficacy in reducing the duration of agranulocytosis in some patients who develop clozapine-induced agranulocytosis. It is currently unknown whether filgrastim is beneficial in the treatment of neutropenia due to BEN. We here, for first the time report a case of a patient with BEN who developed agranulocytosis both during the first clozapine trial for schizophrenia and during the rechallenge, despite early stabilization with filgrastim treatment, which highlights the failure of filgrastim in treating BEN.Funding AcknowledgementsNo funding.

scholarly journals Safety of adjuvant gemcitabine plus cisplatin chemotherapy in a patient with bilateral ureteral cancer undergoing hemodialysis

2021 ◽  
Author(s):  
Yumiko Goto ◽  
Kent Kanao ◽  
Kazuhiro Matsumoto ◽  
Ikuo Kobayashi ◽  
Keishi Kajikawa ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Standard Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Old Japanese ◽  
Left And Right ◽  
The Common ◽  
Grade 3 ◽  
Stimulating Factor

AbstractAn 80 year old Japanese man with bilateral ureteral cancer underwent laparoscopic bilateral nephroureterectomy and lymph-node dissection. The pathological stage of the left and right ureteral tumors was pT3pN0M0. He received two courses of adjuvant gemcitabine and cisplatin chemotherapy while undergoing hemodialysis. The standard dose of gemcitabine and 50% of the standard dose of cisplatin were administered on the same day. Hemodialysis was started 6 h after gemcitabine administration and 1 h after cisplatin administration. The side effects were evaluated according to the Common Terminology Criteria for Adverse Events v4.0. In the first course, Grade 4 side effects including leukopenia, neutropenia, and thrombocytopenia were observed. He was treated with granulocyte colony-stimulating factor and platelet transfusion. Because the second course was administered without reducing the doses, granulocyte colony-stimulating factor was administered prophylactically, and Grade 4 side effects were reduced to Grade 3. Gemcitabine plus cisplatin chemotherapy can be administered safely in a patient with advanced ureteral cancer undergoing hemodialysis by adequately managing adverse events.

An Examination of Ethical Issues Raised in the Pretreatment of Normal Volunteer Granulocyte Donors With Granulocyte Colony-Stimulating Factor

1999 ◽  
Vol 123 (6) ◽  
pp. 508-513
Author(s):  
Emily E. Volk ◽  
Ronald E. Domen ◽  
Martin L. Smith
Keyword(s):  
Side Effects ◽  
Ethical Issues ◽  
Normal Volunteer ◽  
Best Interests ◽  
Institutional Review Boards ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Healthy Individuals ◽  
Institutional Review ◽  
Stimulating Factor

Abstract Objective.—To explore some of the ethical issues surrounding the administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals for the purpose of retrieval of granulocytes. Design.—Review of the historical precedent of drug administration to normal blood donors and review of the literature concerning the side effects of G-CSF administration to healthy individuals, particularly as related to granulocyte collection. We identify and discuss some of the ethical questions regarding this issue. Results.—Although the short-term side effects of G-CSF use in normal donors are generally felt to be benign, little is known about the long-term side effects. Ethical questions regarding the administration of this drug to normal donors for the purpose of collecting large numbers of granulocytes include the following: Does the potential benefit to a patient/recipient justify the unknown risks to the medicated granulocyte donor? Who should act as an advocate for donors so that their best interests are protected? What is the role and quality of informed consent for donors undergoing G-CSF administration? Is monetary compensation appropriate for donors administered G-CSF as part of a research protocol? Conclusions.—We recommend the establishment of a donor registry to collect the needed data on the side effects of G-CSF on normal donors. Until adequate data are collected, the use of G-CSF and similar agents in normal donors should be regarded as experimental and subject to review by institutional review boards.

scholarly journals EFFICACY OF GRANULOCYTE COLONY-STIMULATING FACTOR AND ENTEROSORPTION IN MELPHALAN-INDUCED BONE MARROW SUPPRESSION IN GUERIN CARCINOMA GRAFTED RATS

2019 ◽  
Vol 5 (1) ◽  
pp. 66-74
Author(s):  
O. O. Shevchuk ◽  
I. M. Todor ◽  
N. Yu. Lukianova ◽  
N. K. Rodionova ◽  
V. G. Nikolaev ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Bone Marrow Suppression ◽  
Limiting Factors ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Efficient Treatment ◽  
Chemotherapy Side Effects ◽  
Oral Adsorbent ◽  
Stimulating Factor

Background. Side effects of antineoplastic agents (especially leukopenia and neutropenia) could be the main limiting factors for efficient treatment. Objective. The research is aimed at the study of myeloprotective capability of biosimilars of granulocyte colony stimulating factor (G-CSF) and granular carbon oral adsorbent C2 in melphalan-induced bone marrow suppression in Guerin carcinoma-grafted rats. Methods. Melphalan at the dose of 5.5 mg/kg was used to promote bone marrow suppression in the Guerin carcinoma grafted rats. To fight myelosuppression, we used filgrastim and its analogue, designed and produced by IEPOR, a recombinant granulocyte colony-stimulating factor (r-GCSF). Carbon granulated enterosorbent C2 was used for enteral sorption therapy (bulk density γ=0.18 g/cm3, diameter of granules 0.15-0.25 mm, BET pore surface – 2162 m2/g). All rats were sacrificed on the 17th day after carcinoma cells inoculation or on the 8th day after Melphalan injection. Results. Alkylating cytostatic agent caused severe leukopenia (by 95.7%), neutropenia (by 73.9%), and thrombocytopenia (by 84.9%) in the experimental rats. Mortality rate was 57%. Filgrastim and enterosorption with carbon oral adsorbent C2 increased the studied indices, but the most prominent results were observed when combination of both factors was used. Studied means did not affect the anti-tumor efficacy of Melphalan alone and in combination. Conclusions. Our results are perspective for further investigation of the efficacy of the combination of carbon oral adsorbents and hematopoietic cytokines in cases of ameliorate anti-cancer chemotherapy side effects, and its implementation into clinics.

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