Down Syndrome as an Independent Risk Factor for Thrombosis in Children.
Authors: Journeycake Janna M. , Brumley Laura E. 
Published: October 2019

Abstract
Thromboembolic complications in children occur at an estimated rate of 5.3 per 10,000 hospitalized children per year. Over the last decade, investigators have determined that underlying medical conditions such as cancer and congenital heart disease (CHD) and the intensive therapies required to manage these conditions are strongly associated with the thromboembolic complications. Recently, we perceived an increase in the incidence of thrombosis in children with Down Syndrome (DS), a chromosomal abnormality which is associated with both CHD and cancer, but there is very little evidence in the medical literature to suggest that it is an independent risk factor for thrombosis. Although, there are case series describing an association of moyamoya disease and DS, only a few case reports describe venous and arterial thrombosis in children with DS, and there is no information about its rate and severity. Therefore, we conducted a retrospective analysis of patients treated at Children’s Medical Center Dallas between January 1, 2000 and November 30, 2005, hypothesizing that thrombosis would be more prevalent in patients with DS (with or without associated co-morbidities) than in children without DS. ICD-9 codes for CHD, DS, cancer, and thromboembolic complications and the CPT codes for the surgical procedures used to correct CHD were used to identify patients of interest. During the study period, the emergency center, ambulatory outpatient areas, and inpatient units saw 729,324 children. Among these, we identified 511 patients with DS (0.07%), 2168 (0.29%) with CHD, and 1182 (0.16%) with cancer. Sixty-one percent (n=311) of the patients with DS also had CHD, and 2.9% (n=15) had cancer. Thrombosis was identified in 398 (5.4 per 10,000 children). The majority (n=220, 55%) developed deep venous thrombosis (DVT), with catheter-related thrombosis (n= 156) being most common. There were 165 (41%) arterial ischemic strokes (AIS), 19 associated with moyamoya disease. Fifteen children with DS developed thrombosis (rate of 293 per 10, 000 children with DS). Among these 15, DVT occurred in 11 (73%) patients and AIS in 5 (33%), 2 with moyamoya. Among the subgroup of patients diagnosed with AIS, DS was not found to be a risk factor for moyamoya disease (OR 5.6, 95% CI 1.05, 30.5, p=0.1). Two patients with DS (13%) had both DVT and AIS. Children diagnosed with DS (OR 57.5, 95% CI 34.2, 96.5, p<0.0001), CHD (OR 129.5, 95% CI 103, 163, p<0.0001), or cancer (OR 57.3, 95% CI 40, 82, p<0.0001) were more likely to develop thrombosis than children without these three diagnoses. Among the children with CHD, having DS did not increase the odds for thrombosis. However, for children with cancer, DS did increase the odds (OR 9.5, 95% CI 2.7, 33.1, p= 0.007). Four of 15 (27%) children with DS did not have cancer or CHD and still had a higher than expected rate of venous and/or arterial thrombosis (OR 60, 95% CI 23, 156, p< 0.0001). In conclusion, the results of this retrospective analysis indicate that DS may be an independent risk factor for thromboembolic disease during childhood. Prospective studies are needed to confirm these findings and explore potential mechanisms.