Background/Purpose: The prevalence of anti-phospholipid antibodies (APL) in children with Down syndrome (DS) is unknown. Furthermore, it is unknown if an intermittent or persistent presence of APL in DS patients makes them at higher risk for thrombosis and strokes. Such knowledge may support the importance of routinely screening DS patients for APL. Our aim is to explore the presence of APL in children with DS compared with healthy children.

Methods:  We screened 61 children with DS and a control group (CG) of 61 matched healthy children for anti-cardiolipin antibodies (aCL), anti-β2 glycoprotein-1 antibodies (anti-β2 GP 1), and lupus anticoagulant (LA) in the absence of recent infections. We repeated the positive tests any time after 12 weeks of the initial testing and counted the final APL-subtype as positive only if the repeated testing was positive. We then considered the participant to be APL-positive if any APL-subtype was positive. A retrospective review of medical records was performed for relevant medical conditions. The appropriate chi-square test was used to test for the difference in the number of participants in each group with positive APL.

Results:  The number of APL-positive tests in DS patients was 12.1%, compared with 1.7% in the controls (p = 0.03), although the titers were generally in the low to moderate range. There was no difference between groups for APL subtypes; however, LA was a better predictor of the presence of APL (p ≤ 0.001). Congenital heart disease was present in 57.1% of APL-positive DS patients. DS patients with known anti-thyroid antibodies or hypothyroidism (n = 19) were negative for APL. None of the DS patients had any history of stroke or thrombosis.

Conclusion: Our results suggest that APL antibodies, specifically using the LA test, may be found in DS patients. Larger confirmatory studies and long-term follow-up are needed to better understand the implications of our results.

Table 1. Demographics of the DS group and CG children.

	DS (n = 61)	CG (n = 61)	P value
Gender: n (%) Males / Females	29 (47.5) / 32 (52.5)	27 (44.3) / 34 (55.7)	0.85
Ethnicity: n (%) Arabic / Non-Arabic	54 (88.5) / 7 (11.5)	45 (73.8) / 16 (26.2)	0.06
Age: (mean ± SD)	9.73 ± 2.14	10 ± 2.14	0.71
Karyotype: n (%) Tri 21 Others *	59 (96.7) 2 (3.3)	NA NA	NA NA
Medical History: n (%) CHD Hypothyroidism Anti-thyroid ** Leukemia Celiac IDDM Moyamoya Neutropenia	28 (45.9) 19 (31.1) 19 (31.1) 2 (3.3) 1 (1.6) 1 (1.6) 1 (1.6) 1 (1.6)	0% 0% 0% 0% 0% 0% 0% 0%	NA NA NA NA NA NA NA NA

* One patient was 46, XY t (14, 21) and another was 48, XXY, +21

** Past presence of any anti-thyroid antibodies with or without thyroid disease

CHD: congenital heart disease, IDDM: Insulin dependent diabetes mellitus

Table 2. Presence of APL in DS group and CG children.

	DS (n = 61)	CG (n = 61)	P value
aCL positive: n (%)	2 (3.3)	0	0.49
Anti-ß2 GP 1 positive: n (%)	1 (1.6)	0	1.00
LA-positive: n (%)	4 (6.9) *	1 (1.7) **	0.20
Any APL positive: n (%)	7 (12.1)	1 (1.7)	0.03

* Number of Down syndrome patients with LA testing = 58

** Number of control subjects with LA testing = 59

Table 3. APL subtypes in DS patients with positive APL.

	N (%) with Positive APL-subtype:	N (%) with Negative APL-subtype:	P value
aCL	2 (28.6)	5 (71.4)	0.01
Anti-ß2 GP 1	1 (14.3)	6 (85.7)	0.12
LA	4 (57.1)	3 (42.9)	≤ 0.001