POS0784 LOW COMPLEMENT LEVELS ARE ASSOCIATED WITH HIGHER MORTALITY IN HOSPITALIZED PATIENTS WITH POSITIVE ANTIPHOSPHOLIPID ANTIBODIES

Abstract

BackgroundAntiphospholipid Syndrome is an autoimmune disease characterized by increased risk for vascular thrombosis (arterial and/or venous) thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. The mechanisms by which aPLs induce thrombosis are unclear; several have been suggested, among them complement activation.(1-2) The complement system is a system of enzymes and regulatory proteins of the innate immune system that play a crucial role in the inflammatory response to various pathogenic stimuli. The complement and coagulation pathways are interconnected, and expanding evidence indicates that complement may be activated in patients with antiphospholipid syndrome (3-5).ObjectivesOur study was intended to better characterize the complicated relations between antiphospholipid antibodies and complement activation among hospitalized patients with antiphospholipid syndrome and its impact on short- and long-term prognosisMethodsA retrospective cohort studies. Clinical and prognostic data of hospitalized patients with antiphospholipid syndrome and a measurement of complement levels (C3 or C4) were obtained. Rates of long-term mortality, one-year mortality, deep vein thrombosis (DVT), and pulmonary emboli (PE) were compared between patients with low complement levels and patients with normal complement levels. Low complement was defined as C3 < 90 mg/dl or C4 < 10 mg/dl. A multivariate analysis was performed to control for Anticardiolipin levels, β₂ macroglobulin levels and RVVT ratio.ResultsComplete data was available for 6,599 patients, of which 712 (11%) had low complement levels. The median age of the cohort was 47.7, and most of the patients were females (56%). Patients with low complement levels had significantly higher mortality rates 30% vs. 18%, p < 0.001 for long-term mortality (Figure 1) and 15% vs. 5%, p < 0.001 for 1 year mortality when compared to patients with normal complement levels. DVT and PE rates were similar (4% vs 3.8%, P = 0.78 and 4% vs 2.4%, P = 0.13 respectively). Results of the multivariate analysis (Table 1) were consistent and showed that patients with low complement levels had 111% higher mortality rates (CI 1.52-2.90, P < 0.001).Table 1.Multivariate Analysis for long term mortalityMultivariate AnalysisOR (CI)pLow Complement2.11 [1.52, 2.90]<0.001Anticardiolipin IGG1.00 [1.00, 1.01]0.243Anticardiolipin IGM0.99 [0.98, 1.00]0.084β₂ IGM1.01 [1.00, 1.01]0.017β₂ IGG1.00 [0.99, 1.00]0.663RVVT Ratio0.99 [0.63, 1.52]0.954Figure 1.Cumulative 10-Year survivalConclusionIn hospitalized patients with high aPLs, low complement levels are associated with significantly higher mortality rates. This finding is in correlation with recent literature, suggesting an important role for complement activation in APS.