Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort

Abstract

Objective

To examine hematological manifestations’ correlates and their impact on damage accrual and mortality in SLE patients from the multiethnic, Latin American, GLADEL cohort.

Methods

In patients with recent SLE diagnosis (≤2 years), the association between follow-up hematological manifestations (per ACR criteria) and socio-demographic and clinical variables was examined by univariable and multivariable logistic regressions; their impact on damage accrual and mortality was examined by Poisson and Cox proportional-hazards regression analyses, respectively.

Results

Of 1437 patients, 948 (66.0%) developed ≥1 hematological manifestation [5.5% hemolytic anemia (AHA), 16.3% thrombocytopenia, and 56.4% lymphopenia] over 4.3 (3.3) follow-up years. Younger age, Mestizo ethnicity, hematologic disorder (at/or before SLE diagnosis), and first damage recorded were associated with hematological manifestations while antimalarials were negatively associated. AHA (at/or before SLE diagnosis), anti-Sm, and anti-RNP antibodies were associated with subsequent AHA occurrence while musculoskeletal involvement was negatively associated. Thrombocytopenia (at/or before SLE diagnosis), AHA, anti-phospholipid antibodies (aPLs), anti-SSA/Ro, anti-SSB/La antibodies, and first damage recorded were associated with later thrombocytopenia occurrence. Lymphopenia (at/or before SLE diagnosis), younger age at diagnosis, Mestizo ethnicity, having medical insurance, and first damage recorded were associated with subsequent lymphopenia occurrence while antimalarials and azathioprine treatment were negatively associated. AHA was associated with damage accrual and mortality after adjusting for variables known to affect these outcomes.

Conclusions

Mestizo ethnicity and early hematological manifestations are risk factors for their subsequent occurrence while antimalarials have a protective effect. The associations between AHA and aPLs and thrombocytopenia were corroborated. AHA contributes independently to damage accrual and diminished survival.

Introduction

Nearly all systemic lupus erythematosus (SLE) patients develop hematological abnormalities, either isolated or in conjunction with other manifestations, sometime during their disease course [1].

Anemia is seen in about 50% of SLE patients being anemia of chronic disease, the most common followed by iron deficiency and autoimmune hemolytic anemias (AHA) [1], [2], [3], [4]. AHA, reported in 5–14% of SLE patients [1], [3], [4], [5], [6], [7], [8], [9], is usually mediated by warm-type IgG anti-erythrocyte antibodies [1], [3], [10], occurs with higher frequency in African Americans and associates with anticardiolipin antibodies (ACLs), thrombotic events, renal involvement, seizures, serositis, lymphopenia, thrombocytopenia, damage accrual, and higher mortality [7], [8], [9], [11], [12], [13], [14].

SLE-associated thrombocytopenia occurs in 7–30% of patients [15], [16], [17], [18], is mostly immune-mediated by anti-platelet antibodies [1], [15], [19]; anti-thrombopoietin and anti-phospholipid antibodies (aPLs) have also been implicated [15], [20]. Thrombocytopenia in SLE has been associated with ACLs, renal involvement, neurological manifestations, AHA, leukopenia, and neutropenia [7], [13], [16], [21] and is an independent predictor of adverse outcomes (higher disease activity, damage accrual, and mortality) [16], [18], [22], [23].

Finally, leukopenia, reported in approximately 50% of patients, especially in those with active disease, may occur due to lymphopenia, neutropenia or both, being lymphopenia the most common SLE hematological manifestation [1], [2], [24]. Circulating cytotoxic lymphocyte antibodies occur in 36–90% of patients; their titers correlate with the degree of lymphopenia [2]. In the LUMINA (lupus in minorities: nature vs. nurture) study, lymphopenia was associated with renal involvement, leukopenia, elevated anti-dsDNA, and anti-Ro antibodies early and during the course of the disease [25]. Marked (≤500/mm³) lymphopenia has been independently associated with disease activity, damage accrual, neuropsychiatric manifestations, fever, and polyarthritis [24], [25], [26].

We hypothesized that these hematological manifestations will be associated with more severe SLE clinical manifestations and will impact damage accrual and mortality. We have now conducted such analyses in patients from Grupo Latinoamericano de Estudio del Lupus (GLADEL), a Latin American SLE cohort [27].