Inherited defects of the protein C anticoagulant system in childhood thrombo-embolism

Abstract

Childhood thrombo-embolism is mostly the result of inherited thrombophilia or vascular insults combined with risk factors such as peripartal asphyxia, fetopathia diabetica, exsiccosis, septicaemia, central lines, congenital heart disease, cancer, trauma, surgery or elevated antiphospholipid antibodies. Inherited thrombophilia includes mainly defects of the protein C pathway, resistance to activated protein C, protein C or protein S deficiency. Resistance to activated protein C, in the majority of cases caused by the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of thrombo-embolism in adults and children. However, since an acquired risk of thrombo-embolic complications frequently masks the inherited deficiency in affected children, children with thrombo-embolism should have adequate laboratory evaluation for inherited coagulation disorders, especially the protein C pathway. Until more data on childhood thrombo-embolism are available, treatment recommendations will continue to be extrapolated from guidelines for adults.

Neonatal symptomatic thromboembolism in Germany: two year survey

“…As the study was carried out between 1992 and 1994, there was no laboratory screening for resistance to activated protein C at this time. Evidence suggests that resistance to activated protein C and further defects of the protein C pathway14 may have a major role in neonatal stroke15 or in neonates with thromboembolism after cardiac catheterisation 6. Preliminary data from a prospective study in neonates and children with central lines show that genetic defects of thrombophilia have a major role in catheter related thrombosis: in a population of 163 children with central lines flushed with low dose heparin (0.15-0.3 IU/ml anti-Xa activity), 15 out of 18 children with familial thrombophilia developed vascular occlusion (Nowak-Göttl et al , unpublished observations).…”

Cerebral venous sinus thrombosis in infancy and childhood: role of genetic and acquired risk factors of thrombophilia

“…However, the role of genetic risk factors for familial thrombophilia including the F R506Q mutation in the factor V (FV) gene (6), which is present in 50% of thrombosis-prone families, inhibitors of the protein C pathway [32] and lipoprotein (a) (Lp(a)) [36] in children with venous sinus thrombosis remains unclear. To determine to what extent genetic or acquired thrombophilia aects the risk of childhood cerebral venous thrombosis, its occurrence was investigated in a population of children with dural venous sinus thrombosis.…”

Pediatric Intracardiac Thrombus: A Diagnostic and Therapeutic Dilemma

“…4 Additional research also suggests that thrombus in children may be secondary to acquired or inherited hypercoagulable conditions. One series suggests that approximately 7% of children with thrombus demonstrated a deficiency in protein S, while 20% demonstrated a deficiency in protein C. 5 In those with hereditary thrombophilias, symptomatic thrombi and thromboembolism manifest in roughly 5% of affected children. 5 However, most studies have noted that children with inherited coagulopathies who develop thrombus also have other previously mentioned associated risk factors as well.…”

“…One series suggests that approximately 7% of children with thrombus demonstrated a deficiency in protein S, while 20% demonstrated a deficiency in protein C. 5 In those with hereditary thrombophilias, symptomatic thrombi and thromboembolism manifest in roughly 5% of affected children. 5 However, most studies have noted that children with inherited coagulopathies who develop thrombus also have other previously mentioned associated risk factors as well. 5,6 Aside from obesity, our patient presented at the onset as a healthy teenager with de novo thrombus and no significant prior medical, family, or drug history.…”

“…5 However, most studies have noted that children with inherited coagulopathies who develop thrombus also have other previously mentioned associated risk factors as well. 5,6 Aside from obesity, our patient presented at the onset as a healthy teenager with de novo thrombus and no significant prior medical, family, or drug history.…”