Background/Purpose: Hypocomplementemia is a common phenomenon in systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS). Robust mechanistic data implicate complement activation in antiphospholipid antibody related thrombosis. However, many questions remain unanswered regarding the clinical implications of hypocomplementemia in SLE and APS. Whether low complement should be considered a risk factor for thrombosis in this population is unknown. This work was undertaken to evaluate the relationship between hypocomplementemia and thrombotic outcomes in SLE patients with antiphospholipid antibodies.

Methods: As part of a longitudinal lupus cohort, thrombotic events were noted at inception and updated at each quarterly visit. Anticardiolipin antibodies and the lupus anticoagulant were measured quarterly. The statistical analysis included patients who were found on longitudinal follow up to have antibodies to cardiolipin or the presence of the lupus anticoagulant. Patients were then categorized according to the type of thrombotic event, the presence of hypocomplementemia (low C3, low C4 and both low C3 and low C4) and type of antiphospholipid antibody encountered. Those with low complement were compared to those without and the odds ratio for each thrombotic outcome was calculated.

Results: 2399 SLE patients were included in this analysis, 1140 (47.5%) had antibodies to cardiolipin and 624 (26.0%) were found to have had a positive lupus anticoagulant. The relationship between the antiphospholipid antibodies, thrombotic outcomes and low C3, low C4 or both is outlined in Table 1. Low C3 and low C4 in combination associated with deep venous thrombosis and stroke in those with anticardiolipin antibodies. This relationship remained significant on multivariate analysis, controlled for ethnicity and gender. The lupus anticoagulant and low C3 and C4 in combination was also associated with stroke. An association was also demonstrated with digital gangrene and low C4 in the presence of the lupus anticoagulant.

Conclusion: Hypocomplementemia (both low C3 and low C4), in the presence of either the lupus anticoagulant or anticardiolipin antibodies, associates with stroke. Low complement, with antibodies to cardiolipin, also associated with deep venous thrombosis. These finding support the mechanistic data implicating the complement system in APS related thrombus formation and indicate that hypocomplementemia, in association with antiphospholipid antibodies may represent an addition risk factor for thrombosis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-systemic-lupus-erythematosus-with-antiphospholipid-antibodies-hypocomplementemia-associates-with-thrombosis/