Case report: Timing of eculizumab treatment in catastrophic antiphospholipid syndrome

Abstract

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition of small-vessel thrombosis with acute multiple-organ involvement and visceral damage. In this report, we present a case of a patient with CAPS who is refractory to conventional therapy. For the first time in a patient with CAPS, marked C5b-9 formation was demonstrated on microvascular endothelial cells, suggesting the usefulness of therapeutic complement inhibition in this setting. Eculizumab, a C5-blocking monoclonal antibody, is remarkably effective in the treatment of different forms of thrombotic microangiopathy by controlling complement system hyperactivation. It halted the "thrombotic storm" and promptly achieved full recovery of thrombocytopenia. However, kidney function did not recover, possibly because eculizumab was administered too late. Conceivably, the timing of treatment is crucial to achieving disease remission before irreversible structural damage occurs in target organs, thereby preventing their complete functional recovery.

Keywords: C5b-9; antiphospholipid syndrome; catastrophic antiphospholipid antibody syndrome (CAPS); complement system; eculizumab; kidney failure; timing.

Figure 1

Patient treatment and outcome from admission until hospital discharge and follow-up.

Figure 2

Ex vivo C5b-9 deposition on cultured human microvascular endothelial cell (HMEC-1) line induced by serum of the patient collected before (PRE-infusion) and 10 days after (POST-infusion) eculizumab treatment. (A, B) HMEC-1 resting (A) or activated with ADP (B) were incubated for 2 h with serum (diluted 1:2 with test medium, Hank’s Balanced Salt Solution (HBSS) with 0.5% Bovine Serum Albumin (BSA)) from the patient or with a control serum pool. At the end of incubation, cells were washed, fixed, and stained with rabbit antihuman complement C5b-9 complex antibody followed by Fluorescein Isothiocyanate (FITC)-conjugated secondary antibody. Fluorescence microscopy was used to view the fluorescent staining on the endothelial cell surface, and the HMEC-1 area covered by C5b-9 staining was calculated by automatic edge detection (Image J software) in 15 high-power fields. For each sample, the highest and lowest values were discarded, and the mean of the other 13 fields was calculated. Values were expressed as the percentage of C5b-9 deposits induced by a pool of sera from 10 healthy controls run in parallel (reference, 100%). Dashed lines indicate the upper and lower limits of the normal range. Data are reported ± SE. ^* p < 0.0001 versus control serum pool; °p < 0.0001 versus patient PRE-infusion. Statistical analysis: ANOVA.