Autoimmune hemolytic anemias

Abstract

UVOD: Autoimunosne hemolitičke anemije (AIHA) heterogena su skupina rijetkih bolesti koje se, ovisno o uzroku, mogu podijeliti na primarne ili sekundarne. Ovisno o vrsti podležećih protutijela, mogu se podijeliti na tople (wAIHA), hladne (cAIHA), miješane (mAIHA) ili paroksizmalnu hladnu hemoglobinuriju (PCH). ----- CILJ: Ispitati kliničke karakteristike odraslih novooboljelih bolesnika s AIHA-om te identificirati čimbenike koji utječu na tijek bolesti. ----- ISPITANICI I METODE: Unicentrična retrospektivna studija provedena u Kliničkom bolničkom centru Zagreb uključila je sve punoljetne novooboljele osobe s AIHA-om koje su imale pozitivan antiglobulinski test (DAT+), u razdoblju od 1. siječnja 2014. do 30. lipnja 2020. Osobe su praćene od dijagnoze do zaključno 26. travnja 2021. Analiza preživljenja, postizanje kompletne remisije (KR) te relapsa bolesti (Re) provedene su uklapanjem u Coxov model propocionalnih hazarda (kovarijance modela: koncentracija hemoglobina (Hb) pri dijagnozi (osim pri analizi Re), dob pri dijagnozi, spol, komorbiditeti (Charlsonin indeks komorbiditeta), etiološka i serološka klasifikacija te terapija rituksimabom). Za pojedine kovarijance izračunat je omjer hazarda (HR). ----- REZULTATI: U navedenom razdoblju bilo je 71 novoobljelih, od kojih je praćenje u vremenu bilo moguće za njih 64; 51% novooboljelih bile su žene, a najčešći tipovi AIHA-e bili su sekundarna (83%) i wAIHA (73%). Većina bolesnika primala je kortikosteroidnu terapiju kao prvu liniju liječenja; rituksimab je primilo 22 (34%) bolesnika, u 13 (59%) bolesnika primijenjen u sklopu prve linije terapije (zajedno s kortikosteroidima). Medijan razdoblja praćenja iznosio je 2,11 (0,60 – 3,49) godina. Stopa smrtnosti iznosila je 19,1 na 100 osoba godina; a značajan utjecaj na smrtnost imali su dob (HR 1,047 (95% CI: 1,02-1,08), p=0,001), komorbiditeti (HR 1,28 (95% CI: 1,05-1,55), p=0,013) te mAIHA vs. wAIHA (HR 0,19 (95% CI: 0 – 0,68), p=0,011). Stopa incidencije KR iznosila je 9,2 na 10 osoba-godina, a značajan utjecaj na KR imali su ženski spol (HR 2,27 (95% CI: 1,01-4,92), p=0,037) i sekundarna AIHA (HR 0,34 (95% CI: 0-0,95), p=0,039). Stopa incidencije relapsa nakon postignute KR iznosila je 1,4 na 10 osoba-godina, a značajan utjecaj na relaps imali su mAIHA vs. wAIHA (HR 181,7 (95% CI: 3-11×103), p=0,038) te dob (HR 0,34 (95% CI: 0-0,96), p=0,04). ----- ZAKLJUČAK: Provedeno istraživanje prikazalo je kliničke karakteristike bolesnika AIHA-om te je kvantificiralo stopu smrtnosti i stope incidencije kompletne remisije i relapsa bolesti, a ujedno je identificiralo čimbenike koje utječu na pojedini promatrani ishod.INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a heterogenous group of rare disorders which, depending upon the underlying etiology, can be classified as primary or secondary. Depending upon the underlying type of autoantibodies, AIHAs can be classified as warm (wAIHA), cold (cAIHA), mixed (mAIHA) or as paroxysmal cold hemoglobinuria (PCH). ----- AIM: To investigate the clinical characteristics of adult patients with AIHA and to identify factors that influence the course of disease. ----- PARTICIPANTS AND METHODS: Non-concurrent unicentric cohort study was performed at the University Hospital Centre Zagreb, which included all adult patients with newly diagnosed AIHA which had a positive direct antiglobulin test (DAT+), in the period from 1 January 2014 to 30 June 2020. All participants were followed until death or until censored, with the end of the follow-up period on 26 April 2021. Survival, complete remission (CR) and disease relapse (Re) were analyzed by fitting the Cox proportional hazards model (covariances: hemoglobin (Hb) concentration at diagnosis (except for Re analysis), age at diagnosis, sex, Charlson comorbidity index, etiological and serological classification, as well as rituximab therapy). Hazard ratio (HR) was calculated for each covariate. ----- RESULTS: During the mentioned time period, 71 DAT+ AIHA patients were newly diagnosed. Follow-up was possible for 64 of them. 51% of newly diagnosed patients were women, and the most common types were secondary (83%) and wAIHA (73%). Most patients received corticosteroids as first line therapy; 34% received rituximab therapy, in 59% of whom it was applied as first line. Median time of follow up was 2,11 (0,60 – 3,49) years. Mortality rate was 19.1 per 100 person-years; significant factors for mortality were age (HR 1,047 (95% CI: 1.0-1.1), p=0.001), comorbidities (HR 1.28 (95% CI: 1.1-1.6), p=0.013) and mAIHA vs. wAIHA (HR 0,19 (95% CI: 0 – 0.7), p=0.011). The incidence rate for CR was 9.2 per 10 person-years; significant factors for CR were female sex (HR 2.27 (95% CI: 1.01-4.9), p=0.037) and secondary AIHA (HR 0.34 (95% CI: 0-0.95), p=0.039). The relapse rate (after CR was achieved) was 1.4 per 10 person-years; significant factors for relapse were mAIHA vs. wAIHA (HR za mAIHA 181.7 (95% CI: 3-11×103), p=0.038) and age (HR 0.34 (95% CI: 0-0.96), p=0.04). ----- CONCLUSION: This study presented the clinical characteristics of DAT+ AIHA patients and quantified mortality rate and incidence rates for complete remission and relapse, as well as identified factors that significantly impact each of the observed outcomes