Background/Purpose: AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) is an international network that has been created to design and conduct APS clinical trials. A basic need of APS ACTION was to accurately assess the relationship between antiphospholipid antibodies (aPL) and the different aPL-associated outcomes, i.e., pregnancy morbidity (PM, comprising pregnancy loss [PrL], early PrL, late PrL, intrauterine growth restriction [IUGR], pre-eclampsia [PEC], severe PEC, eclampsia [EC], and HELLP syndrome), stroke (ST), myocardial infarction (MI), and deep venous thrombosis (DVT).
Methods: The search for “aPL” and multiple keywords regarding the outcomes of interest was completed in PubMed. A total of 117 full-text papers assessing the rate of aPL positivity in patients and controls were retrieved; 97 of these studies statistically investigated the relationship between aPL and clinical outcomes. We analyzed the reported association between aPL and the clinical outcomes for each criteria test (anticardiolipin antibodies [aCL], anti-β2-glycoprotein-I antibodies [aβ22GPI], and lupus anticoagulant test [LA]), and then for all three criteria tests combined.
Results: The table reports the number of studies, median number of patients [IQR], and the association between aPL and related outcomes based on different aPL tests. There was a 25-100% association between aPL and clinical outcomes depending on the aPL type and outcome analyzed. However, the literature was impinged by several limitations including: a) only 12% of the studies used the three available criteria aPL tests; b) 4% used a cut-off conforming to international guidelines (low-titer cut-off was used in 22% and medium-titer cut-off in 8%); c) the sample sizes were rather small, with 64% including less than 100 patients; d) only 19% of the studies confirmed that aPL was persistent; and e) 57% of the studies did not have a prospective design.
Conclusion: The positive association between aPL and clinical outcomes included in the Updated Sapporo APS Classification Criteria is not supported by every study, the association is particularly weak for early PrL, IUGR, PEC, EC and HELLP Syndrome. Given the limitations of the literature, well-designed general population studies as well as large scale APS registries are warranted to further investigate the relationship between aPL and related manifestations. We hope that APS ACTION will help improving upon existing aPL/APS literature.
|
OUTCOME (# of studies) (Median # of patients [IQR]) |
aCL (+) Association (N (+)/N, %) |
ab2GPI (+) Association (N (+)/N, %)
|
LA (+) Association (N (+)/N, %) |
Overall aPL (+) Association (N (+)/N, %) |
|
PM |
|
|
|
|
|
– PrL (n: 9) (114 [48.25-213.75]) |
7/8 (88%) |
3/4 (75%) |
7/7 (100%) |
8/9 (89%) |
|
– Early PrL (n: 3) (113 [113-137]) |
2/3 (66.6%) |
1/2 (50%) |
– |
2/3 (67%) |
|
– Late PrL (n: 7) (96 [26-158]) |
6/8 (75%) |
2/3 (67%) |
5/6 (83%) |
5/7 (71%) |
|
– IUGR (n: 3) (22 [14-36]) |
1/3 (33%) |
– |
0/1 (0%) |
1/3 (33%) |
|
– PEC (n: 12) (87.5 31.75-216.75]) |
5/11 (46%) |
0/1 (0%) |
3/5 (60%) |
5/12 (42%) |
|
– Severe PEC (n: 8) (41.4 23.75-74.75]) |
5/7 (71%) |
1/2 (50%) |
4/4 (100%) |
6/8 (75%) |
|
– EC (n: 4) (25 [14-25.5]) |
0/3 (0%) |
– |
0/1 (0%) |
1/3 (25%) |
|
– HELLP (n: 3) (44.5 [25.5-59.75]) |
1/3 (33%) |
0/2 (0%) |
0/1 (0%) |
2/3 (67%) |
|
ST (n: 21) (116.5 [81-189.25]) |
15/21 (71%) |
2/4 (50%) |
6 /9 (67%) |
10/21 (48%) |
|
MI (n: 24) (90 [34-167]) |
12/22 (55%) |
5/7 (71%) |
3/5 (60%) |
12/24 (50%) |
|
DVT (n: 21) (122 [92-317]) |
8 /19 (42%) |
4/6 (67%) |
7/11 (64%) |
10/21 (48%) |
Disclosure:
C. B. Chighizola,
None;
L. Andreoli,
None;
A. Banzato,
None;
G. Ramires de Jesus,
None;
G. J. Pons-Estel,
None;
D. Erkan,
GlaxoSmithKline,
8;
O. B. O. APS Action,
None.
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