Title: Increased
Risk of Hemolytic Anemia
Associated With Antiphospholipid Antibodies in
Patients With Systemic Lupus Erythematosus: A Systematic
Review and Meta-Analysis.

Background/Purpose :
Hemolytic anemia (HA) is
present in patients with systemic lupus erythematosus
(SLE), and the role of antiphospholipid antibodies (aPL) is controversial. Therefore
our objective was to estimate the risk of HA associated with aPL in patients with SLE.

Methods : Studies were selected if they
investigated the association between aPL
and HA in SLE patients and if aPL-negative patients
were included for comparison. Data sources were Pubmed,
Embase, Cochrane Library, hand search, congress
abstracts, and reference lists of studies, without language restrictions. Risk
estimates were independently extracted by 2 investigators. Pooled effect
estimates were obtained by using the Mantel-Haenszel method
(random effects).

Results: Of 1992 identified abstracts, 38
primary studies and 1 abstract (16 cohorts, 4 case-control,
19 cross-sectional) met inclusion criteria, including 7967 SLE patients according
to ACR criteria and 974 cases of HA. Prevalence of HA in aPL-positive
vs. aPL-negative SLE patients was 22.4 % (n=488/2177)
vs. 8.4% (n=486/5790), respectively. Compared with SLE patients without HA, the
overall pooled odds ratios (OR) for HA in aPL-positive
SLE patients was 3.22 (95% confidence interval [CI], 2.40-4.32) (Figure 1). Of
note, in studies explicitly reporting a positive Coombs test, the risk of HA
was significantly increased (10 studies, OR=3.17 [95% CI, 1.93-5.20]). The risk
of HA was the highest for lupus anticoagulant (LA) (12 studies, OR=4.58 [95% CI,
2.62-8.04]) and IgG anti-β₂-glycoprotein
I antibodies (4 studies, OR=3.95 [95% CI, 1.46-10.71]). Risk of HA was also
significantly increased in SLE patients with either IgG
or IgM anticardiolipin
antibodies (aCL) (10 studies, OR=2.27 [95% CI, 1.71-3.00];
12 studies, OR=2.89 [95% CI, 2.16-3.87], respectively)
and IgM anti-β₂-glycoprotein I
antibodies (3 studies, OR=3.00 [95% CI, 1.48-6.07]).

Conclusion : In SLE
patients, aPL-positivity is associated with a significant
2- to 4-fold increased risk for HA. These findings a) confirm that an aPL-related mechanism can contribute to HA in SLE patients and
b) suggest that HA could be associated with aPL in SLE patients.

Figure 1