Background: Comprehensive laboratory testing for genetic and acquired thrombophilia traits is recommended for the evaluation of children with thrombosis by the Perinatal and Pediatric Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH), and is becoming a standard of care. Evidence to date suggests that the incidence, etiology, and pathophysiology of thrombosis in the perinatal period exhibit important differences from those of older infants and children. The frequency with which thrombophilia laboratory evaluation reveals clinically useful information in perinatal thrombosis has not been well established.

Objective: To determine the prevalence and nature of thrombophilia in perinatal thrombosis.

Methods: All children had been referred to the Thrombosis/Thrombophilia Program at The Children’s Hospital, Denver, and were consecutively recruited for participation in collection of laboratory and clinical data for this research. Perinatal thrombosis was defined as a venous and/or arterial thrombotic event diagnosed at birth or within the first month of life. The ISTH-recommended thrombophilia laboratory panel was performed clinically, and consisted of the following: a complete blood count; detection of the factor V Leiden (FVL) and prothrombin 20210 (PT20210) polymorphisms by PCR; functional assays of antithrombin (AT), protein C (PC), factor VIII (FVIII), and the lupus anticoagulant (LA); immunologic assays of lipoprotein(a) [Lp(a)], free protein S (PS), and anticardiolipin antibody (ACA); and detection of plasma homocysteine (Hcy) concentration by gas chromatograph mass spectroscopy. Antiphospholipid antibody testing was performed in the neonate and/or mother. Age-related abnormal values for non-genetic tests were defined as PC and PS < 20%, AT < 25%, FVIII > 150%, Lp(a) > 30 mg/dL, and homocysteine > 13.9 mM.

Results: Forty neonates with thrombosis were referred for evaluation during an 8-year period, of which data were available in 37. Sixteen (43%) had venous thrombosis (including cerebral sinovenous, inferior vena caval, renal vein thrombosis, and isolated pulmonary embolism), an equal number had isolated ischemic arterial stroke in the distribution of the middle cerebral artery, and the remaining 5 (14%) had both arterial and venous thrombosis. Twenty-one (57%) of the 37 neonates with thrombosis exhibited thrombophilia upon comprehensive testing. Among these children, two had three-trait thrombophilia (low PC + low PS + high FVIII), four had two-trait thrombophilia (PT20210 + FVL; PT20210 + high Lp(a); low PC + low AT; and LA + ACA), and fifteen had single thrombophilia traits (low PC in 4; high Lp(a) or high FVIII in 3 each; LA, ACA, low AT, or polycythemia in 1 each).

Conclusions: Upon comprehensive standardized laboratory assessment, thrombophilia was detected in greater than half of all children with perinatal thrombosis. Given that in many cases the identified abnormalities impact upon antithrombotic management and call for follow-up testing to guide duration of antithrombotic therapy and the need for secondary prophylaxis as well as consideration of future pregnancy management, comprehensive thrombophilia testing is warranted in perinatal thrombosis.