Hypercoagulable states

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Chapter 26 HYPERCOAGULABLE STATES

Theodore X. O’Connell

General Discussion

The overall incidence of venous thrombotic events (TE) in children is estimated to be between 0.7 and 1.9 per 100,000 children. Newborns are at particularly high risk of TE, presumably because of their immature coagulation system marked by decreased activity of anticoagulant factors, including antithrombin, protein C, and protein S.

Hypercoagulable conditions are classified as primary, an inherited condition, or secondary, an acquired state. The inherited disorders include factor V Leiden; prothrombin G20210A gene mutation; hyperhomocysteinemia; dysfibrinogenemia; elevated factor VIII level; and deficiencies of antithrombin, protein C, and protein S. Acquired hypercoagulable conditions include the antiphospholipid syndrome (lupus anticoagulant and anticardiolipin antibody); hyperhomocysteinemia; and the commonly known thrombosis risk factors of pregnancy, cancer, and estrogen-containing medications.

Until recently, the assessment and management of children with thromboembolism have relied almost exclusively on data from the adult experience with thrombosis. Developmental differences in the coagulation system of children and differences in medical problems underlying the development of thrombosis in children are now being considered in the management of pediatric thrombosis.

Most case of TE within the first year of life are associated with central venous access devices. In addition, spontaneous thromboses in the renal, caval, portal, or hepatic venous systems have been reported in neonates. These TE often are associated with acquired predisposing factors such as sepsis, peripartum asphyxia, dehydration, or maternal diabetes. By 6 months of age, infants’ levels of almost all of the coagulation factors reach adult values, and the risk of thrombosis decreases. TEs after infancy are more often multifactorial and associated with other medical conditions, outlined below.

Inherited prothrombotic disorders are usually suspected in children with an unexplained cause for thrombosis, a positive family history of thrombosis, a history of recurrent TE, or thromboses in an unusual location. The most common inherited prothrombotic disorders are due to mutations in the factor V Leiden gene or prothrombin gene, followed by deficiencies of antithrombin (AT), protein C, and protein S. Hyperhomocysteinemia and dysfibrinogenemia are also among the more common causes of thrombosis. The relative risk of recurrent TE increases with the number of inherited susceptibility genes.

No standardized approach to screening patients for hypercoagulability has been established. The cost-effectiveness of performing the laboratory examination is unknown, and the work-up typically is expensive. Most clinicians take into consideration patient risk factors when deciding on the need for an extensive work-up. A work-up should be considered when there is an unexplained cause for thrombosis, a positive family history of thrombosis, a history of recurrent TE, or thromboses in an unusual location.

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