Background/Purpose: One proposed mechanism of aPL-mediated thrombosis is disruption of the AnxA5 shield, allowing initiation of coagulation reactions on phospholipid surfaces.  The AnxA5-RA measures the resistance to AnxA5 anticoagulant activity in the plasmas of aPL-positive patients. Based on in vitro studies, HCQ interferes with aPL binding to cell surfaces and helps repair disrupted AnxA5 shields; however, no in vivo  human studies exist. The purpose of this ongoing prospective study is to determine the effect of HCQ on the AnxA5-RA in aPL-positive patients; here we present the preliminary baseline results.

 

Methods:  As part of the ongoing study, aPL-positive patients (positive lupus anticoagulant [LA], anticardiolipin antibody [aCL] ≥ 40GPL/MPL, and/or anti-β₂-glycoprotein-I [aβ₂GPI] antibody ≥ 40 SGU/SMU at two time points at least 12 weeks apart) starting HCQ are recruited to give blood at baseline, 6 weeks, and 12 weeks (primary outcome measure: AnxA5-RA; secondary outcome measures: LA, aCL, aβ₂GPI, D-dimer and anti-domain-I β₂GPI antibody [aDI-β₂GPI]). As a control group, aPL (LA, aCL, and aβ₂GPI)-negative systemic lupus erythematosus (SLE) patients starting HCQ are also recruited. For the purpose of this preliminary analysis, we compared the baseline characteristics of aPL-positive patients to aPL-negative SLE patients (Mann-Whitney test).

Results: Baseline data from 15 aPL-positive patients (mean age 43.3 ± 12.0 years [range 27-61], 10 [67%] female, 13 [87%] Caucasian; 10 had antiphospholipid syndrome, 5 asymptomatic aPL) were compared to 7 aPL-negative SLE patients (mean age 40.0 ± 16.3 years [range 22-64], 7 [100%] female, 4 [57%] Caucasian). Thirteen (87%) of the 15 aPL-positive patients had positive AnxA5-RA; 9/13 (69%) were triple aPL-positive, 2/13 (15%) were double aPL-positive (both aCL- and aβ₂GPI-positive) and 2/13 (15%) were single aPL-positive (one aCL- and one aβ₂GPI-positive only). Seven (47%) of 15 aPL-positive patients had aDI-β₂GPI; 5/7 (71%) were triple aPL-positive and 2/7 (29%) were single aPL-positive (aβ₂GPI). No patients in the control group had positive AnxA5-RA or aDI-β₂GPI. Baseline AnxA5-RA and aDI-β₂GPI results, but not D-dimer levels, differed in aPL-positive patients versus aPL-negative SLE controls (Table). 

	aPL (+), n:15	aPL (-) SLE, n: 7	p	Reference Range
AnxA5-RA (%)				Negative ≥153 Borderline 140-152.9 Positive <140
– Mean ± SD	130.1 ± 15.6	175.7 ± 24.5
– Median (IQR)	127.9 (117.7-132.2)	173.9 (156.8-193.7)	0.0004
aDI-β2GPI (mg/L)				Negative <1.66 Borderline 1.66-2.29 Positive >2.29
– Mean ± SD	4.11 ± 3.94	0.70 ± 0.56
– Median (IQR)	2.14 (1.52-7.16)	0.70 (0.20-1.09)	0.002
D-dimer (µg/mL)				Normal 0.8-2.3
– Mean ± SD	1.87 ± 0.67	1.93 ± 1.64
– Median (IQR)	1.73 (1.60-2.34)	1.28 (1.14-2.00)	0.37
AnxA5-RA: Annexin-A5 resistance assay; aDI-β2GPI: anti-domain-I β2-glycoprotein-I antibody; SD: standard deviation; IQR: interquartile range

Conclusion:  Based on the preliminary baseline results of our ongoing prospective study, aPL-positive patients detected based on criteria tests also have positive AnxA5-RA and aDI-β₂GPI; our findings support the use of these non-criteria tests to detect aPL in the clinical setting. The effect of HCQ on outcome measures will be determined by the analysis of our longitudinal data.

Funding:  This investigation was supported by grant UL1RR024996 of the Clinical and Translational Science Center at Weill Cornell Medical College and the Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-hydroxychloroquine-hcq-on-the-annexin-a5-resistance-assay-anxa5-ra-in-antiphospholipid-antibody-apl-positive-patients-preliminary-results-of-an-ongoing-prospective-study/