DOCSLIB.ORG

Managing Clozapine-Induced Neutropenia and Agranulocytosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Managing Clozapine-Induced Neutropenia and Agranulocytosis Savvy Psychopharmacology Managing clozapine-induced neutropenia and agranulocytosis Jeremy S. Daniel, PharmD, BCPS, BCPP, and Tonya Gross, PharmD r. S, age 43, has schizophrenia and Clozapine-induced neutropenia been stable on clozapine for 6 years Clozapine was approved in 1989 for man- M after several other antipsychotic aging treatment-resistant schizophrenia regimens failed. Mr. S also has a history of after demonstrating better efficacy than hypertension, dyslipidemia, and gastroesoph- chlorpromazine.1 However, the adverse ageal reflux disorder. His medication regi- effects of neutropenia (white blood cell men includes clozapine, 400 mg/d, lisinopril, count [WBC] <3,000/μL) and agranulocyto- Vicki L. Ellingrod, 20 mg/d, atorvastatin, 40 mg/d, omeprazole, sis (ANC <500/μL3) leading to death were PharmD, FCCP 40 mg/d, and a multivitamin. During routine reported in later studies.2,3 One study in Department Editor blood monitoring, Mr. S shows a significant the United Kingdom and Ireland reported drop in absolute neutrophil count (ANC) a prevalence of 2.9% for neutropenia and (750/µL) (reference range, 1,500 to 8,000 µL). 0.8% for agranulocytosis among patients Mr. S , who is African American, has no history taking clozapine.3 Because of this risk, the of benign ethnic neutropenia (BEN) or ANC FDA mandated WBC and ANC monitor- <1,000/µL. While reviewing his chart, clini- ing before initiating clozapine and periodi- cians note that Mr. S had an ANC of 1,350/µL cally thereafter. In October 2015, the Risk 3 years earlier in 2013. Because a complete Evaluation and Mitigation Strategies pro- workup reveals no other cause for this lab gram for clozapine updated recommended abnormality, we determine that is clozapine- ANC levels and eliminated WBC monitor- induced. Mr. S’s physician asks about treat- ing. ANC monitoring frequencies are sum- ment options that would allow him to stay marized in the Table (page 52).1 on clozapine. The exact mechanism of clozapine- induced neutropenia is unknown, although Because of clozapine’s efficacy in treatment- it is possible it stems from the drug’s effect on resistant schizophrenia, many psychiatrists white blood cell precursors.2 Neutropenia aim to manage patients who develop abnor- mal laboratory values without discontinu- Practice Points ing clozapine. This article will examine the • There is lack of evidence for long-term evidence behind 2 potential management use of filgrastim for clozapine-induced Savvy Psychopharmacology strategies. neutropenia and agranulocytosis; short- is produced in partnership with the College Dr. Daniel is Assistant Professor, South Dakota State University, term treatment is recommended. of Psychiatric and Neurologic College of Pharmacy, Brookings, South Dakota, and Clinical • There is potential risk of lithium masking Pharmacist, Avera McKennan Hospital and University Health Center, Pharmacists Sioux Falls, South Dakota. Dr. Gross is PGY-2 Psychiatric Pharmacy the preliminary state of neutropenia cpnp.org Resident, Avera McKennan Hospital and University Health Center, leading to severe agranulocytosis. mhc.cpnp.org (journal) Sioux Falls, South Dakota. Disclosures • Patients who experience neutropenia with The authors report no financial relationship with any company whose clozapine are at an increased risk for a products are mentioned in this article or with manufacturers of repeat neutropenia on rechallenge. Current Psychiatry competing products. Vol. 15, No. 12 51 Savvy Psychopharmacology Table Absolute neutrophil count monitoring frequencies with clozapine ANC level Monitoring Initiation • Weekly for 6 months General population: ≥1,500/μL • Every 2 weeks from 6 to 12 months • Monthly after 12 months BEN population: ≥1,000/μL (Obtain at least 2 baseline ANC values before initiating treatment) Mild neutropenia BEN population: 1,000 to 1,499/μL • No additional monitoring needed. ANC still in normal range General population: Clinical Point • Monitor ANC 3 times weekly until ≥1,500/μL • Then can return to patient’s last ANC monitoring interval Most patients Moderate neutropeniaa BEN population: rechallenged with 500 to 999/μL • Monitor ANC 3 times weekly until ≥1,000/μL or the patient’s baseline clozapine experience • Then monitor ANC weekly for 4 weeks, then return to patient’s a more severe, faster, last ANC monitoring interval General population: and longer episode • Interrupt clozapine of neutropenia • Monitor ANC daily until ≥1,000/μL, then restart clozapine • Then monitor ANC 3 times weekly until ≥1,500/μL • Then monitor ANC weekly for 4 weeks • Then return to patient’s last ANC monitoring interval Severe neutropeniaa BEN populationb: <500/μL • Discontinue clozapine • Daily ANC until ≥500/μL • Then 3 times weekly until ANC is more than or equal to the patient’s established baseline General populationb: • Discontinue clozapine • Daily ANC until ≥1,000/μL • Then 3 times weekly until ANC ≥1,500/μL aRecommend hematology consultation bMay rechallenge if prescriber determines benefits outweigh risks ANC: absolute neutrophil count; BEN: benign ethnic neutropenia Source: Reference 1 typically appears within 3 months of clo- is viewed as a “rescue” treatment. zapine initiation; however, delayed cases Filgrastim’s mechanism of action is related have been reported. Additionally, the risk to neutrophil production and prolif- is higher in certain patient populations eration. Several articles from the 1990s Discuss this article at (African heritage, Yemenite, West Indians, reported efficacy in the short-term man- www.facebook.com/ and Arab). Patients with a lower ANC agement of low WBC or ANC. However, CurrentPsychiatry at clozapine initiation and advanced age few articles, mainly case reports, have appear to be at higher risk.2 looked at long-term use of these agents. One article examined 3 patients, average Filgrastim age 45, who developed neutropenia dur- The use of granulocyte-colony stimu- ing clozapine treatment.4 Filgrastim at an Current Psychiatry 52 December 2016 lating factor, such as filgrastim, often average dosage of 0.6 to 0.9 mg/week was Savvy Psychopharmacology used successfully. The dosage was reduced Related Resources to 0.3 mg/week in 1 patient, although • Clozapine REMS Program. www.clozapinerems.com. neutropenia returned. • Newman BM, Newman WJ. Rediscovering clozapine: Because of the lack of literature regard- adverse effects develop—what should you do now? ing long-term therapy, it is recommended Current Psychiatry. 2016;15(8):40-46,48,49. to consider short-term treatment with fil- • Whiskey E, Taylor D. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities. CNS Drugs. grastim to normalize ANC after a severe 2007;21(1):25-35. drop in a symptomatic patient. Physicians Drug Brand Names also must consider the potential barriers Atorvastatin • Lipitor Lisinopril • Prinivil to filgrastim treatment including adverse Chlorpromazine • Thorazine Lithium • Eskalith, Lithobid effects, such as allergic reactions, bone pain, Clozapine • Clozaril Omeprazole • Prilosec Fligrastim • Neupogen and thrombocytopenia, and high cost. Clinical Point Adjunctive lithium There is more Lithium could cause leukocytosis, which could balance neutropenia induced by clo- possible that lithium will not protect a evidence supporting zapine. One of the largest studies evaluat- patient from clozapine-induced neutro- the efficacy ing lithium therapy with clozapine-induced penia or agranulocytosis, and can lead to of lithium neutropenia and agranulocytosis studied serious adverse events. for clozapine- 25 patients taking clozapine with a previ- When deciding whether to rechallenge a induced neutropenia ous “red result” (WBC <3,000/μL, ANC patient on clozapine who had a prior epi- <1,500/μL, or platelets <50,000/μL).3 sode of moderate or severe neutropenia or than filgrastim Lithium treatment was started before or agranulocytosis, a risk vs benefit discussion simultaneously with the reinitiation of is necessary. One study found that 20 of clozapine in most patients; the remaining 53 patients (38%) experienced a repeat patients started treatment at a later date. dyscrasia when rechallenged.5 Of these Only 1 of 25 patients experienced a repeat patients, most experienced a lower ANC “red result.” The average lithium level that presented faster and took longer to was 0.54 mEq/L. resolve.5 If a patient has experienced true It is important to remember that ini- agranulocytosis, the recommendation is to tiating adjunctive lithium carries risk. not rechallenge clozapine. Adverse effects include gastrointestinal upset, tremors, polyuria, polydipsia, and References 1. Clozapine [package insert]. North Wales, PA: TEVA nephrotoxicity. Pharmaceuticals USA; 2015. Additionally, there is risk that lithium 2. Lundblad W, Azzam PN, Gopalan P, et al. Medical management of patients on clozapine: a guide for internists. J Hosp Med. simply masks the preliminary states of 2015;8(8):537-543. neutropenia leading to a more severe 3. Kanaan RA, Kerwin RW. Lithium and clozapine rechallenge: 3 a retrospective case analysis. J Clin Psychiatry. 2006;67(5): agranulocytosis without warning. Again, 756-760. the mechanism of action of clozapine- 4. Hägg S, Rosenius S, Spigset O. Long-term combination treatment with clozapine and filgrastim in patients with induced neutropenia is thought to be clozapine-induced agranulocytosis. Int Clin Psychopharmacol. related to the drug’s effect on WBC precur- 2003;18(3):173-174. 5. Dunk LR, Annan LJ, Andrews CD. Rechallenge with clozapine sors. The mechanism of lithium-induced following leucopenia or neutropenia during previous therapy. leukocytosis is unknown, therefore it’s Br J Psychiatry. 2006;188:255-263. Current Psychiatry Vol. 15, No. 12 53.
Load more

Recommended publications
  • Lithium Sulfate
    SIGMA-ALDRICH sigma-aldrich.com Material Safety Data Sheet Version 4.1 Revision Date 09/14/2012 Print Date 03/12/2014 1. PRODUCT AND COMPANY IDENTIFICATION Product name : Lithium sulfate Product Number : 203653 Brand : Aldrich Supplier : Sigma-Aldrich 3050 Spruce Street SAINT LOUIS MO 63103 USA Telephone : +1 800-325-5832 Fax : +1 800-325-5052 Emergency Phone # (For : (314) 776-6555 both supplier and manufacturer) Preparation Information : Sigma-Aldrich Corporation Product Safety - Americas Region 1-800-521-8956 2. HAZARDS IDENTIFICATION Emergency Overview OSHA Hazards Target Organ Effect, Harmful by ingestion. Target Organs Central nervous system, Kidney, Cardiovascular system. GHS Classification Acute toxicity, Oral (Category 4) GHS Label elements, including precautionary statements Pictogram Signal word Warning Hazard statement(s) H302 Harmful if swallowed. Precautionary none statement(s) HMIS Classification Health hazard: 1 Chronic Health Hazard: * Flammability: 0 Physical hazards: 0 NFPA Rating Health hazard: 1 Fire: 0 Reactivity Hazard: 0 Potential Health Effects Inhalation May be harmful if inhaled. May cause respiratory tract irritation. Aldrich - 203653 Page 1 of 7 Skin Harmful if absorbed through skin. May cause skin irritation. Eyes May cause eye irritation. Ingestion Harmful if swallowed. 3. COMPOSITION/INFORMATION ON INGREDIENTS Formula : Li2O4S Molecular Weight : 109.94 g/mol Component Concentration Lithium sulphate CAS-No. 10377-48-7 - EC-No. 233-820-4 4. FIRST AID MEASURES General advice Move out of dangerous area.Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
    [Show full text]
  • Digitalcommons@UNMC Granulocytopenia
    University of Nebraska Medical Center DigitalCommons@UNMC MD Theses Special Collections 5-1-1936 Granulocytopenia Howard E. Mitchell University of Nebraska Medical Center This manuscript is historical in nature and may not reflect current medical research and practice. Search PubMed for current research. Follow this and additional works at: https://digitalcommons.unmc.edu/mdtheses Part of the Medical Education Commons Recommended Citation Mitchell, Howard E., "Granulocytopenia" (1936). MD Theses. 457. https://digitalcommons.unmc.edu/mdtheses/457 This Thesis is brought to you for free and open access by the Special Collections at DigitalCommons@UNMC. It has been accepted for inclusion in MD Theses by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. G PA~lULOCYTOPENI A SENIOR THESIS By Howard E. Mitchell April 17, 1936 TABLE OF CONT'ENTS Introduction Definition • · 1 History . • • • 1 Nomenclature • • • • • 4 ClassificBtion • • • • 6 Physiology • • • • .10 Etiology • • 22 Geographic Distribution • 23 Age, Sex, and R9ce • • ·• 23 Occupation • .. • • • • .. • 23 Ba.cteria • • • • .. 24 Glandu18.r Dysfunction • • • 27 Radiation • • • • 28 Allergy • • • 28 Chemotactic and Maturation Factors • • 28 Chemicals • • • • • 30 Pathology • • • • • 36 Symptoms • • • • • • • 43 DiEtgnosis • • • • • .. • • • • • .. • 4'7 Prognosis 48 '" • • • • • • • • • • • • Treatment • • • • • • • • 49 Non"'specific Therapy • • • • .. 50 Transfusion • • • • .. 51 X-Ray • • • • • • • • • 52 Liver ·Extract • • • • • • • 53 Nucleotides • • • • • • • • • • • 53 General Ca.re • • • • • • • • 57 Conclusion • • • • • • • • • 58 480805 INTHODUCTION Although t~ere is reference in literature of the Nineteenth Century to syndromes similating the disease (granulocytopenia) 9.8 W(~ know it todes, it "vas not un­ til the year 1922 that Schultz 8ctually described his C8se as a disease entity and by so doing, stimulated the interest of tne medical profession to further in­ vestigation.
    [Show full text]
  • Chediak Higashi Syndrome Masquerading As Acute Leukemia / Storage Disorder - a Rare Case Report
    International Journal of Research in Medical Sciences Asif Baig M et al. Int J Res Med Sci. 2015 Jul;3(7):1785-1787 www.msjonline.org pISSN 2320-6071 | eISSN 2320-6012 DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20150271 Case Report Chediak Higashi Syndrome masquerading as acute leukemia / storage disorder - A rare case report Mirza Asif Baig1,*, Anil Sirasgi2 1Former Asst. professor, BLDUs Shri B.M. Patil Medical College, Bijapure, Karnataka, India 2Associate professor, ESI Medical College, Gulbarga, Karnataka, India Received: 19 April 2015 Revised: 09 May 2015 Accepted: 23 May 2015 *Correspondence: Dr. Mirza Asif Baig, E-mail: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Chediak higashi Syndrome (CHS) is a rare autosomal recessive multisystem disorder with a defect in granule morphogenesis with giant lysosomes in leucocyte and other cells. CHS is a rare disease, approximately 200 cases have been reported so far. It was described in detail by Chediak in 1952 and Higashi in 1954. 1½ year old male child presented with multiple hypopigment patches on lower extremities, light colored hair, Hepatosplenomegaly and generalised Lymphadenopathy. PBS shows giant prominent liliac to purple granules in neutrophils, band forms, few lymphocytes and monocytes. Bone marrow is hypercellular showing giant prominent gray blue to purple heterogeneous granules often multiple seen in many myeloid precursors, Neutrophils, few lymphocytes and monocytes.
    [Show full text]
  • Clozapine, Agranulocytosis, and Benign Ethnic Neutropenia
    EDITORIAL 545 Postgrad Med J: first published as 10.1136/pgmj.2004.031641 on 2 September 2005. Downloaded from Pharmacology and toxicology ethnic groups in the Middle East, ....................................................................................... including Yemenite Jews and Jordanians, have BEN.12 13 BEN has only been reported in ethnic groups that have Clozapine, agranulocytosis, and tanned or dark skin.13 Subjects with BEN do not show increased incidence of benign ethnic neutropenia infections, and their response to infec- tions is similar to those without BEN.13 S Rajagopal ................................................................................... CLINICAL IMPLICATIONS In the United Kingdom and Ireland, the Current knowledge and clinical implications Clozaril patient monitoring service (CPMS) supervises the prescribing of clozapine and the haematological test- lozapine is an atypical antipsycho- agranulocytosis, is more common in ing (Clozaril is the brand name of tic that is effective in treatment black people.6 A white cell count spike clozapine). The CPMS uses a lower cut resistant schizophrenia.1 The of 15% or more above the immediately C off point for patients with BEN than for National Institute for Health and preceding measurement may predict the general population (table 1). A Clinical Excellence (NICE) guidelines agranulocytosis within the next ‘‘green’’ alert indicates satisfactory for schizophrenia specify that ‘‘in indi- 75 days.7 However, as these differences count, an ‘‘amber’’ alert requires a viduals with evidence of treatment between the risk factors for agranulocy- repeat FBC test while clozapine can be resistant schizophrenia, clozapine tosis and neutropenia have been extra- should be introduced at the earliest polated primarily from epidemiological continued, and a ‘‘red’’ alert warrants opportunity’’.2 studies, they may be subject to change immediate cessation of clozapine.
    [Show full text]
  • Severe Agranulocytosis in Two Patients with Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms
    Acta Derm Venereol 2016; 96: 842–843 SHORT COMMUNICATION Severe Agranulocytosis in Two Patients with Drug-induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms Miyuki Kato, Yoko Kano*, Yohei Sato and Tetsuo Shiohara Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa Mitaka, Tokyo 181-8611, Japan. *E-mail: [email protected] Accepted Mar 24, 2016; Epub ahead of print Mar 30, 2016 Drug-induced hypersensitivity syndrome/drug reac- No evidence was seen of lymphoma or other haematological tion with eosinophilia and systemic symptoms (DIHS/ malignancies. Granulocyte-colony stimulating factor (G-CSF) DRESS) is a life-threatening adverse reaction characteri- and intravenous immunoglobulin at 5 g/day were administered for 5 days. As high-grade fever continued, antibiotics were zed by skin rashes, fever, leukocytosis with eosinophilia started. During the appearance of agranulocytosis, atypical and/or atypical lymphocytosis, lymph node enlargement, lymphocytosis (2–11%) was detected. On day 24 after onset, and liver and/or renal dysfunctions (1, 2). A wide variety leucocyte count was normalized, but liver dysfunction ap- of other involvements have also been reported, including peared (aspartate aminotransferase (AST) 276 IU/l (normal limbic encephalitis, myocarditis, and gastrointestinal < 33 IU/l); alanine aminotransferase (ALT) 159 IU/l (normal < 30 IU/l)). Renal function was also exacerbated (BUN 86.6 disease, developing during the course of the disease mg/dl; Cr 2.8 mg/dl). Seven days later, leucocytes overshot (3–5). It has been demonstrated that human herpesvirus to 21.3 × 109/l (neutrophil 81.0%; eosinophil 0.5%; monocyte 6 (HHV-6), Epstein-Barr virus (EBV) and cytomegalo- 8%; lymphocyte 10%; atypical lymphocyte 0.5%).
    [Show full text]
  • Management and Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus
    REVIEW Management and treatment of lithium- induced nephrogenic diabetes insipidus Christopher K Finch†, Lithium carbonate is a well documented cause of nephrogenic diabetes insipidus, with as Tyson WA Brooks, many as 10 to 15% of patients taking lithium developing this condition. Clinicians have Peggy Yam & Kristi W Kelley been well aware of lithium toxicity for many years; however, the treatment of this drug- induced condition has generally been remedied by discontinuation of the medication or a †Author for correspondence Methodist University reduction in dose. For those patients unresponsive to traditional treatment measures, Hospital, Department several pharmacotherapeutic regimens have been documented as being effective for the of Pharmacy, University of management of lithium-induced diabetes insipidus including hydrochlorothiazide, Tennessee, College of Pharmacy, 1265 Union Ave., amiloride, indomethacin, desmopressin and correction of serum lithium levels. Memphis, TN 38104, USA Tel.: +1 901 516 2954 Fax: +1 901 516 8178 [email protected] Lithium carbonate is well known for its wide use associated with a mutation(s) of vasopressin in bipolar disorders due to its mood stabilizing receptors. Acquired causes are tubulointerstitial properties. It is also employed in aggression dis- disease (e.g., sickle cell disease, amyloidosis, orders, post-traumatic stress disorders, conduct obstructive uropathy), electrolyte disorders (e.g., disorders and even as adjunctive therapy in hypokalemia and hypercalcemia), pregnancy, or depression. Lithium has many well documented conditions induced by a drug (e.g., lithium, adverse effects as well as a relatively narrow ther- demeclocycline, amphotericin B and apeutic range of 0.4 to 0.8 mmol/l. Clinically vincristine) [3,4]. Lithium is the most common significant adverse effects include polyuria, mus- cause of drug-induced nephrogenic DI [5].
    [Show full text]
  • Agranulocytic Angina
    University of Nebraska Medical Center DigitalCommons@UNMC MD Theses Special Collections 5-1-1939 Agranulocytic angina Louis T. Davies University of Nebraska Medical Center This manuscript is historical in nature and may not reflect current medical research and practice. Search PubMed for current research. Follow this and additional works at: https://digitalcommons.unmc.edu/mdtheses Part of the Medical Education Commons Recommended Citation Davies, Louis T., "Agranulocytic angina" (1939). MD Theses. 737. https://digitalcommons.unmc.edu/mdtheses/737 This Thesis is brought to you for free and open access by the Special Collections at DigitalCommons@UNMC. It has been accepted for inclusion in MD Theses by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. AGRANULOCYTIC ANGINA by LOUIS T. DAVIES Presented to the College of Medicine, University of Nebraska, Omaha, 1939 TABLE OF CONTENTS Introduction • . 1 Definition •• . • • 2 History . 3 Etiology ••• . • • 7 Classification .• 16 Symptoms and Course • . • • • 20 Experimental Work • • •• 40 Pathological Anatomy • • • . 43 Diagnosis and Differential Diagnosis •• . • 54 Therapy Prognosis • • • • • . 55 Discussion and Summary • • • • • • • 67 Conclusions • • • • • • • • • • • • • 73 ·Bibliography • • • • • • • • • • 75 * * * * * * 481028 _,,,....... ·- INTRODUCTION Agranulocytic Angina for the past seventeen years has been highly discussed both in medical centers and in literature. During this time the understanding of the disease has developed in the curriculum of the medical profession. Since 1922, when first described as a clinical entity by Schultz, it has been reported more frequently as the years passed until at the present time agranulocytosis is recognized widely as a disease process. Just as with the development of any medical problem this has been laden with various opinions on its course, etiology, etc., all of which has served to confuse the searching medical mind as to its true standing.
    [Show full text]
  • Fatal Cerebral Hemorrhage Revealing Acute Lymphoblastic Leukemia with Leukostasis
    www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 6 June 2020 | ISSN: 2320-2882 Fatal cerebral hemorrhage revealing acute lymphoblastic leukemia with leukostasis 1Said Khallikane ,2 Mehdi Samali,3Aziz Benakrout, 4Abderrazzak Sabir, 5Samir Siah 1. Service of Anesthesiology and Intensive Care Unit, Third Military Hospital, Laayoune, Morocco 2. Service of Anesthesiology and Intensive Care Unit, Third Military Hospital, Laayoune, Morocco 3. Service of Anesthesiology and Intensive Care Unit, Military Teaching Mohammed V Hospital, Rabat, Morocco 4. Medico-Surgical Pole of laayoune, Sakia El Hamra Region, Service of Gastro-Enterology and Proctology, Third Military Hospital, Laayoune, Morocco 5. Service of Anesthesiology and Intensive Care Unit of Severe Burn Management, Military Teaching Mohammed V Hospital, Faculty of Medicine and Pharmacy of Rabat, Morocco 1. Service of Anesthesiology and Intensive Care Unit, Third Military Hospital, Laayoune, Morocco 1. Service of Cardiovascular Anesthesiology and Cardiac Intensive Care Unit, Mohammed V Military Teaching Hospital, Rabat, Morocco SUMMARY Neurological involvement is frequent in leukemia but is rarely the inaugural event. We report the case of a 15-year-old boy whose acute lymphoblastic leukemia was revealed by fatal cerebral hemorrhage associated with sepsis secondary to lung infection. Intracerebral hemorrhage remains a cause of death in hematologic malignancies. The patient presented with thrombocytopenia (24,000/mm3), leucostasis and hypofibrinogemia (1.10 g/L). Despite maximal medical and surgical treatment (platelets and fresh- frozen plasma transfusions, red blood cells transfusion, and craniotomy discharge), the patient died. The risk of death is high, and surgical treatment has not proven superior to medical therapy in terms of mortality rates and 6-month survival.
    [Show full text]
  • Subchronic Lithium Treatment Increases the Anxiolytic-Like Effect of Mirtazapine on the Expression of Contextual Title Conditioned Fear
    Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual Title conditioned fear Author(s) An, Yan; Inoue, Takeshi; Kitaichi, Yuji; Nakagawa, Shin; Wang, Ce; Chen, Chong; Song, Ning; Kusumi, Ichiro European journal of pharmacology, 747, 13-17 Citation https://doi.org/10.1016/j.ejphar.2014.11.009 Issue Date 2015-01-15 Doc URL http://hdl.handle.net/2115/58243 Type article (author version) File Information AnManuscript.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear Yan Ana, Takeshi Inouea*, Yuji Kitaichia, Shin Nakagawaa, Ce Wangb, Chong Chena, Ning Songa, Ichiro Kusumia a Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan b Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan Number of figures: 3 Corresponding address: Takeshi Inoue, Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan Phone: +81(11)706-5160 Fax: +81(11)706-5081 E-mail: [email protected] 1 Abstract Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual fear conditioning test in rats, an animal model of anxiety or fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned fear.
    [Show full text]
  • Lithium Sulfate, Technical Grade, Min. 99.0 %
    TECHNICAL DATA SHEET Date of Issue: 2018/02/15 Lithium Sulfate, technical grade, min. 99.0 % CAS-No. 10377-48-7 EC-No. 233-820-4 REACH No. 01-2119968668-14 Molecular Formula Li2O4S Product Number 401142 APPLICATION Additive for manufacturing special glass mixtures. Used for marking of chemical products. Additive in the building material industry. SPECIFICATION Li2SO4 min 99.0 % H2O (105 °C) max. 0.4 % Na max. 0.1 % K max. 0.05 % Fe max. 0.002 % Mg max. 0.01 % Heavy metals (as Pb) max. 0.004 % PHYSICAL PROPERTIES Appearance crystalline Color colorless to white Melting point/ range 860 °C Density 2.2 g/cm3 at 20 °C Bulk density ca. 800 kg/m3 Water solubility 342 g/L at 25 °C The information presented herein is believed to be accurate and reliable, but is presented without guarantee or responsibility on the part of Albemarle Corporation and its subsidiaries and affiliates. It is the responsibility of the user to comply with all applicable laws and regulations and to provide for a safe workplace. The user should consider any health or safety hazards or information contained herein only as a guide, and should take those precautions which are necessary or prudent to instruct employees and to develop work practice procedures in order to promote a safe work environment. Further, nothing contained herein shall be taken as an inducement or recommendation to manufacture or use any of the herein materials or processes in violation of existing or future patent. Technical data sheets may change frequently. You can download the latest version from our website www.albemarle-lithium.com.
    [Show full text]
  • Microbiology Chapter 19 Outline
    Microbiology Chapter 19 Outline Introduction (p. 515) 1. Hay fever, transplant rejection, and autoimmunity are examples of harmful immune reactions. 2. Immunosuppression is inhibition of the immune system. 3. Superantigens activate many T cell receptors that can cause adverse host responses. Hypersensitivity (pp. 516–526) 1. Hypersensitivity reactions represent immunological responses to an antigen (allergen) that lead to tissue damage rather than immunity. 2. Hypersensitivity reactions occur when a person has been sensitized to an antigen. 3. Hypersensitivity reactions can be divided into four classes: types I, II, and III are immediate reactions based on humoral immunity, and type IV is a delayed reaction based on cell-mediated immunity. Allergies and the Microbiome (p. 516) 4. Childhood exposure to microbes may decrease development of allergies. Type I (Anaphylactic) Reactions (pp. 516–522) 5. Anaphylactic reactions involve the production of IgE antibodies that bind to mast cells and basophils to sensitize the host. 6. The binding of two adjacent IgE antibodies to an antigen causes the target cell to release chemical mediators, such as histamine, leukotrienes, and prostaglandins, which cause the observed allergic reactions. 7. Systemic anaphylaxis may develop in minutes after injection or ingestion of the antigen; this may result in circulatory collapse and death. 8. Localized anaphylaxis is exemplified by hives, hay fever, and asthma. 9. Skin testing is useful in determining sensitivity to an antigen. 10. Desensitization to an antigen can be achieved by repeated injections of the antigen, which leads to the formation of blocking (IgG) antibodies. Microbiology Chapter 19 Outline Type II (Cytotoxic) Reactions (pp. 522–524) 11.
    [Show full text]
  • Congenital Neutropenia in a Newborn
    Journal of Perinatology (2011) 31, S22–S23 r 2011 Nature America, Inc. All rights reserved. 0743-8346/11 www.nature.com/jp ORIGINAL ARTICLE Congenital neutropenia in a newborn K Walkovich and LA Boxer Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, MI, USA in HAX1, ELANE (previously ELA2), GFI1, WAS, CSF3R and Severe congenital neutropenia (SCN) is a genetically heterogenous, rare G6PC3.6,7 Regardless of the mode of inheritance or specific À3 disorder defined by a persistent absolute neutrophil count <500k mm mutation, newborns with SCN have severe neutropenia, defined with neutrophil maturation arrest at the promyelocyte stage and an as an absolute neutrophil count (ANC) <500 k mmÀ3, often increased risk for infection as well as a propensity towards developing appreciable at birth or shortly thereafter.1,8 Frequent episodes of myelodysplastic syndrome and acute myelogenous leukemia. We report a fever, skin infections, gingivitis, stomatitis, pneumonia and case of incidentally identified SCN in a full-term, otherwise healthy infant perirectal abscesses are common in the first few months of life and girl. Routine complete blood counts obtained for follow up of ABO before the advent of G-CSF therapy death from overwhelming incompatibility-induced jaundice and anemia identified mild neutropenia serious infection was common by 1 year of age.8 Prompt diagnosis at birth followed by severe persistent neutropenia by 1 week of birth. Genetic of SCN in infancy and initiation of treatment to prevent infection is testing confirmed the clinical suspicion of SCN with the identification of a crucial to decreasing morbidity and mortality.
    [Show full text]