Editing Clozapine (section)

====Benign ethnic neutropenia====

Benign reductions in neutrophils are observed in individuals of all ethnic backgrounds.  Ethnic neutropenia (BEN), neutropenia without immune dysfunction or increased liability to infection, is not due to abnormal neutrophil production; although, the exact aetiology of the reduction in circulating cells remains unknown. BEN is associated with several ethnic groups, but in particular those with Black African and West African ancestry.<ref>{{cite journal | vauthors = Atallah-Yunes SA, Ready A, Newburger PE | title = Benign ethnic neutropenia | journal = Blood Reviews | volume = 37 | pages = 100586 | date = September 2019 | pmid = 31255364 | pmc = 6702066 | doi = 10.1016/j.blre.2019.06.003 }}</ref> A difficulty with the use of clozapine is that neutrophil counts have been standardised on white populations.<ref>{{cite journal | vauthors = Haddy TB, Rana SR, Castro O | title = Benign ethnic neutropenia: what is a normal absolute neutrophil count? | journal = The Journal of Laboratory and Clinical Medicine | volume = 133 | issue = 1 | pages = 15–22 | date = January 1999 | pmid = 10385477 | doi = 10.1053/lc.1999.v133.a94931 }}</ref> For significant numbers of black patients the standard neutrophil count thresholds did not permit clozapine use, as the thresholds did not take BEN into account. Since 2002, clozapine monitoring services in the UK have used reference ranges 0.5 × 10<sup>9</sup>/l lower for patients with haematologically confirmed BEN and similar adjustments are available in the current US criteria, although with lower permissible minima.<ref name="Silva 20451253211015070">{{cite journal | vauthors = Silva E, Higgins M, Hammer B, Stephenson P | title = Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital | journal = Therapeutic Advances in Psychopharmacology | volume = 11 | pages = 20451253211015070 | date = January 2021 | pmid = 34221348 | pmc = 8221694 | doi = 10.1177/20451253211015070 }}</ref><ref name="Nielsen_2016">{{cite journal | vauthors = Nielsen J, Young C, Ifteni P, Kishimoto T, Xiang YT, Schulte PF, Correll CU, Taylor D | title = Worldwide Differences in Regulations of Clozapine Use | journal = CNS Drugs | volume = 30 | issue = 2 | pages = 149–161 | date = February 2016 | pmid = 26884144 | doi = 10.1007/s40263-016-0311-1 | s2cid = 23395968 }}</ref><ref>{{cite journal | vauthors = Rajagopal S | title = Clozapine, agranulocytosis, and benign ethnic neutropenia | journal = Postgraduate Medical Journal | volume = 81 | issue = 959 | pages = 545–546 | date = September 2005 | pmid = 16143678 | pmc = 1743348 | doi = 10.1136/pgmj.2004.031161 }}</ref> But even then significant numbers of black patients will not be eligible even though the low neutrophil counts do not in their case reflect disease. The [[Duffy antigen system|Duffy]]–Null polymorphism, which protects against some types of malaria, is predictive of BEN.<ref>{{cite journal | vauthors = Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh WC, Cheng CY, Coresh J, Boerwinkle E, Li M, Waliszewska A, Neubauer J, Li R, Leak TS, Ekunwe L, Files JC, Hardy CL, Zmuda JM, Taylor HA, Ziv E, Harris TB, Wilson JG | title = Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene | journal = PLOS Genetics | volume = 5 | issue = 1 | pages = e1000360 | date = January 2009 | pmid = 19180233 | pmc = 2628742 | doi = 10.1371/journal.pgen.1000360 | doi-access = free }}</ref><ref name="tandfonline.com">{{Cite journal | vauthors = Silva E |date=28 August 2024 |title=Childhood onset violence and early onset schizophrenia. A molecular diagnosis of 15q13.2-13.3 duplication syndrome and the effects on insight and engagement |url=https://www.tandfonline.com/doi/full/10.1080/14789949.2024.2396348 |journal=The Journal of Forensic Psychiatry & Psychology |volume=35 |issue=6 |language=en |pages=984–995 |doi=10.1080/14789949.2024.2396348 |issn=1478-9949}}</ref> In the UK the Royal College of Psychiatrists recommends consideration of Duffy typing when using or considering clozapine for people with Black or Middle Eastern ancestry, in the UK this can be requested from the International Blood Group Reference laboratory based in Bristol.<ref name="tandfonline.com"/>