Background Low complement is common in systemic lupus erythematosus (SLE) and is considered in classification criteria and disease activity indices. Recent evidence supports the hypothesis that the activation of complement is also important in the antiphospholipid syndrome (APS), coating platelets and contributing to thrombus formation. The successful treatment of catastrophic APS with the terminal complement inhibitor, eculizumab, has been reported, supporting this hypothesis.
Objectives This work was undertaken to evaluate the relationship between hypocomplementemia and thrombotic outcomes in SLE patients with antiphospholipid antibodies (APL).
Methods As part of a longitudinal lupus cohort, the presence of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin) and thrombotic events, both venous and arterial, were updated quarterly. Statistical analysis included only patients who were found on longitudinal follow up to have one or more APL, i.e. antibodies to cardiolipin, or the presence of the lupus anticoagulant (LAC). Patients were then categorized by thrombotic event, the presence of hypocomplementemia (low C3, low C4 and both low C3 and C4) and type of APL. Those with low complement were compared to those without and the odds ratio for each thrombotic outcome calculated.
Results 2399 patients were included, 1140 (47.5%) had antibodies to cardiolipin and 624 (26.0%) a positive LAC. The relationship between the antiphospholipid antibodies, thrombotic outcomes and low C3, low C4 or both in combination is outlined in Table 1.
Conclusions In patients with anticardiolipin antibodies, the presence of hypocomplementemia (both low C3 + C4) associates strongly with DVT and stroke. Hypocomplementemia in the setting of the LAC was also associated with stroke whilst low C4 alone associated with digital gangrene. These findings are supportive of the robust mechanistic data involving the complement system in APS. They also raise the question as to whether hypocomplementemia should be considered a further risk factor for thrombosis in SLE patients with positive antiphospholipid antibodies in whom to date many traditional risk factors have been implicated.
Disclosure of Interest None declared