High plasma C5a and C5b-9 levels during quiescent phases are associated to severe antiphospholipid syndrome subsets

Clin Exp Rheumatol. 2022 Nov;40(11):2088-2096. doi: 10.55563/clinexprheumatol/7cinzu. Epub 2022 Mar 1.


Objectives: High plasma C5a and C5b-9 levels are considered a clear sign of complement activation. We aimed to evaluate the clinical significance of these two complement activation products during quiescent phases of thrombotic antiphospholipid syndrome (APS) by comparing their plasma levels in the different clinical subsets and relating them to the clinical characteristics and antiphospholipid antibody profile of the patients.

Methods: The three patient subsets studied were: i) thrombotic patients responsive to anti-vitamin K therapy (TAPS); ii) patients with refractory to vitamin K antagonists recurrent thrombosis (RAPS); iii) patients diagnosed with catastrophic APS (CAPS). Plasma C5a and C5b-9 levels were assessed using commercial ELISA assays.

Resulyts: Sixty-two quiescent APS patients were recruited: 40 were affected by TAPS, 13 by RAPS and 9 by CAPS. Data analysis showed that the TAPS patients had significantly lower levels of both complement activation products with respect to the RAPS and CAPS patients. In addition, C5a and/or C5b-9 significantly prevailed in the patients with small-vessel thrombosis, just as C5b-9 did in the triple antiphospholipid antibody positive patients. The ROC curve showed that the best cut-offs for C5a and C5b-9 levels had a higher sensitivity, specificity and likelihood ratio in the CAPS and RAPS groups than they did in the TAPS subset.

Conclusions: These results suggest that the persistence of high plasma C5b-9 and C5a levels during quiescent phases identifies APS patients with more severe disease who may develop rethrombosis and benefit from complement inhibition treatment during an acute disease phase.

MeSH terms

  • Antibodies, Antiphospholipid
  • Anticoagulants / therapeutic use
  • Antiphospholipid Syndrome* / complications
  • Antiphospholipid Syndrome* / diagnosis
  • Antiphospholipid Syndrome* / drug therapy
  • Complement Membrane Attack Complex
  • Humans
  • Thrombosis* / drug therapy
  • Thrombosis* / etiology


  • Complement Membrane Attack Complex
  • Antibodies, Antiphospholipid
  • Anticoagulants