The CDC Hemostasis and Thrombosis Centers (HTC) Pilot Sites: Data From the Pediatric Registry.

Venous thrombosis (VTE) is a rare disorder in children, and its overall incidence, pathophysiology, and outcomes remain poorly defined. Registries and cohort studies including those from Canada, Germany, Colorado, and others have provided seminal observations on the incidence, age distribution, associated conditions, diagnostic modalities, location, and treatment patterns for children and have resulted in greater awareness and improvements in clinical practice.

The Division of Blood Disorders of the Centers for Disease Control and Prevention (CDC) in collaboration with eight Thrombosis and Hemostasis Centers Patient Registry began in August 2003 to characterize clinical features, treatments, and services provided to the individuals referred.

As of March 2009, 316 children and adolescents from birth to 21 years were enrolled at six of the sites. About half of the patients (48%) were referred from the inpatient setting. Patients were predominantly of white (84%) or black (13%) race and median age was 15.6 years (newborn-21 years). Patients were stratified by age; 178 (56%) were adolescents (≥15 years), 75 (24%) age 7 to 14, 38 (12%) age 1 to 6. 25 (8%) were infants (<12 months). Gender distribution over the entire cohort was similar (54% female), however gender differed as age increased; 64% of infants were male decreasing to 42% in adolescents (p for trend=0.01). Site of thrombosis differed by age. In adolescents, 70% of VTE events occurred in the lower extremity, while cerebral sinus venous thrombosis (CSVT) was the most common site in infants (42%). Prevalence of lower extremity VTE increased with age (p for trend < .0001) while prevalence of CSVT (p<.0001) and abdominal VTE decreased with age (p=0.003). Pulmonary embolism (PE) was more common in the adolescent group (38%, p<.0001). Associated underlying conditions were found in 183 (58%) and also differed by age. Infection (16.8%) was the most common associated condition across all age groups, central venous lines (CVLs) were present in 11% and 4% had cancer. However among infants, CVL (32%), prematurity (24%) and infection (24%) were the most common while infection (10.1%) surgery (10.1%) and oral contraceptive use among females (23.1%) were concurrent for adolescents. Thrombophilia was identified in 86 (27%), of which antiphospholipid antibodies (APA) were the most common (15%). Recurrent VTE occurred in 46 (15%), of which 25 (54%) had one or more thrombophilic traits. No underlying cause or risk factor was found in 98 (31%). Most (85%) of the patients received anticoagulation treatment/management at the center. Low molecular weight heparin (LMWH) was the most commonly used therapy (54%), followed by oral anticoagulation (50%), unfractionated heparin (UFH) (12%), thrombolysis (4%), and embolectomy in 2%.Oral anticoagulation use increased with age (p<.0001).

These data represent one of the largest prospective cohorts of pediatric thrombosis published to date, and includes patients referred from the tertiary care inpatient, as well as the outpatient community. In contrast to earlier registry data, the pediatric thrombosis centers participating in this study are seeing a predominance of lower extremity VTE in adolescent females with acquired risk factors including oral contraceptives and APA, in addition to other underlying medical conditions. The study additionally documented a high rate of thrombus recurrence in children with thrombophilia and advances the debate on the value of routine thrombophilia testing in children with VTE. Although CVLs remain a substantial risk for VTE, their presence in this cohort was surprisingly low. This appears to result primarily from the rarity of CVL associated thrombosis in the adolescents and from the relatively low representation of children with cancer. The data confirm changes in anticoagulation management in favor of LMWH. Finally, the high proportion of pediatric patients with recurrent VTE highlights a need for outcome data to determine optimal methods for primary and secondary prevention of VTE and its sequellae.

No relevant conflicts of interest to declare.