Maternal thrombophilia and neonatal thrombosis

Abstract

In neonates and infants, numerous clinical and environmental conditions lead to elevated thrombin generation and subsequent thrombus formation. Genetic prothrombotic defects (protein C, protein S and antithrombin deficiency, mutations of coagulation factor V and factor II, elevated lipoprotein (a)) have been established as risk factors of thromboembolic events in neonates and infants. The interpretation of the laboratory evaluation relies on age-dependent normal reference values. Because appropriate clinical trials are missing in these age groups, treatment recommendations are adapted from small-scale studies in neonates and infants and from guidelines relating to adult patient protocols. Secondary long-term anticoagulation should be administered on an individual basis.

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

“…Heller and colleagues recommended that neonates with TE should undergo an extensive screening, including resistance to activated protein C (APC-R), protein C, protein S, and antithrombin activity, concentration of clottable fi brinogen, plasminogen activity, activities of coagulation factors VIIIC and XII, Lp(a), histidine-rich glycoprotein, heparin cofactor II, antiphospholipid antibodies, lupus anticoagulants, as well as fasting homocysteine concentrations. In addition, DNA-based assays (ie, factor V G1691A mutation, factor II G20210A variant and MTHFR C677T genotype) should be performed (Heller and Nowak-Gottl 2003). Whereas DNA-based mutation analysis can be performed at any time point, protein-based assays should not be carried out in the fi rst 6-8 months after the event and oral anticoagulation is recommended to be discontinued at least 14-30 days before plasma samples for thrombophilia diagnosis are drawn (Heller and Nowak-Gottl 2003).…”

“…In addition, DNA-based assays (ie, factor V G1691A mutation, factor II G20210A variant and MTHFR C677T genotype) should be performed (Heller and Nowak-Gottl 2003). Whereas DNA-based mutation analysis can be performed at any time point, protein-based assays should not be carried out in the fi rst 6-8 months after the event and oral anticoagulation is recommended to be discontinued at least 14-30 days before plasma samples for thrombophilia diagnosis are drawn (Heller and Nowak-Gottl 2003).…”

“…Most clinicians would agree not to treat catheter-induced thrombosis in a patient without congenital thrombophilia with long-term anticoagulation. However, in patients with single prothrombotic traits, anticoagulation for 3 to 12 months after the onset of the event is recommended (Heller and Nowak-Gottl 2003). Although data published by Kurnik and colleagues give evidence that symptomatic recurrent thromboembolism is not common in children with neonatal arterial ischemic stroke (Kurnik et al 2003), anticoagulation with LMWH or low dose aspirin in children with arterial vascular occlusion or ischemic stroke is recommended by some (Heller and Nowak-Gottl 2003;Strater et al 2001).…”

The preterm infant with thrombosis

“…In addition, acquired prothrombotic risk factors like hyperhomocystenemia, increased lipoprotein a and acquired antiphospholipid antibodies and lupus anticoagulant play a role 1–3 15 35–37. However, the contribution of genetic or acquired thrombophilia in the causation of thrombosis in the preterm infant is unknown.…”

Perinatal stroke: a case-based review

“…Heller and colleagues have suggested that tests based on DNA mutation analysis (such as factor V Leiden or methylene tetrahydrofolate reductase, MTHFR) can be performed at any age. Protein-based assays should be delegated to be done at ∼6 months of age [21]. Certainly, when thrombophilia workup is performed in the neonatal period for protein-based assays, it should be repeated at a later age.…”