Introduction

Venous thromboembolism (venous TE; VTE) is a rare disease that was increasingly recognized and diagnosed in pediatrics in the past decade, usually as a secondary complication of primary underlying diseases such as sepsis, cancer, congenital heart disease, elevated endogenous testosterone, or after therapeutic interventions such as central venous lines (Table 10.1) [1–13]. Pediatric VTE is a severe disease for which long-term outcomes include lack of thrombus resolution in 50% of cases and the development of post-thrombotic syndrome (PTS) in nearly one-fourth of patients [8–11]. Within the entire childhood population, neonates are at the greatest risk for VTE (5.1/100,000 live births per year in Caucasian children) [1,2,6,14], with a second peak in incidence during puberty and adolescence. The annual incidence of venous events was estimated to be 0.07 to 0.14 per 10,000 children, or 5.3 per 10,000 hospital admissions of children and 24 per 10,000 admissions of neonates to neonatal intensive care units [1,6,12–14].

To date, the results of single studies on the risk of VTE onset and recurrence associated with inherited thrombophilia (IT) are contradictory or inconclusive, mainly due to lack of statistical power. Apart from acquired thrombophilic abnormalities such as antiphospholipid antibodies [15–17], deficiencies of antithrombin, protein C, or protein S and the coagulation factor V (G1691A), and factor II (G20210A) variants have been established as risk factors for incident VTE events in adults [18–23]. The ITs have been described as additional risk factors in populations of children with provoked and unprovoked VTE, with and without underlying disease [24–56].

Follow-up data for VTE recurrence in children are available from a few reports and suggest a recurrence rate of approximately 3% in neonates, 6–11% at 2 years in largely unselected cases (provoked and unprovoked incident VTE), and 21% in children with unprovoked VTE [7,10,12,13,38,48,49,51,54,56].