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• In Latin American SLE patients, severe thrombocytopenia is a rare manifestation. • Mestizo ethnicity and baseline AIHA are predictors of severe thrombocytopenia. • Middle/high socioeconomic status protects against severe thrombocytopenia. To examine the predictors of the occurrence of severe thrombocytopenia and its impact on damage accrual and mortality in SLE patients. Factors associated with time to severe thrombocytopenia (platelet count ≤20,000/mm3) occurring from the onset of SLE symptoms were assessed by Cox proportional hazards regressions. The association of severe thrombocytopenia with mortality was evaluated by logistic regression analyses while its impact on damage was by negative binomial regression. Of 1,217 patients, 33 (2.7%) developed severe thrombocytopenia over a mean (SD) follow-up time of 5.9 (3.6) years. The median time from the onset of SLE symptoms to severe thrombocytopenia occurrence was 22 months (IQR 8.7–62.0). Mestizo (60.6%) was the predominant ethnic group, followed by Caucasian (27.3%), while African Latin American exhibited the lowest frequency (12.1%). By multivariable analysis, Mestizo ethnicity (HR 2.67, 95% CI 1.12–6.37, p = 0.027), and autoimmune hemolytic anemia (AIHA) at baseline (HR 3.99; 95% CI 1.05–15.19, p = 0.042) were associated with a shorter time to the occurrence of severe thrombocytopenia while middle/high socioeconomic status (HR 0.23; 95% CI 0.08–0.69, p = 0.008) was associated with a longer time. Severe thrombocytopenia contributed neither to damage nor to mortality. Severe thrombocytopenia occurs during the early course of SLE. Mestizo ethnicity and AIHA at baseline emerged as independent predictors of a shorter time to severe thrombocytopenia occurrence while a middle/high socioeconomic status seems to be protective against its occurrence. Damage and mortality did not seem to be impacted by the occurrence of severe thrombocytopenia. [Display omitted] [ABSTRACT FROM AUTHOR]