Summary. Thromboembolic phenomena, frequently observed in children with cancer who are undergoing chemotherapy, can cause significant morbidity and, less frequently, mortality. Many contributory factors have been identified. Whether the recently identified and most common coagulation defect predisposing to thrombosis, factor V Leiden, is associated with thrombosis in this setting, has not been explored. The current study was undertaken to determine the prevalence of the factor V Leiden mutation in children with cancer who developed thromboembolic phenomena as compared to those with cancer who did not. Genomic DNA was amplified using the polymerase chain reaction (PCR), followed by digestion of the amplification product with the restriction enzyme MnlI. The digested PCR products were then sizefractionated to classify samples as heterozygous, homozygous or normal for the factor V Leiden mutation. 67 children with cancer were evaluated for the factor V Leiden mutation. One of 32 children with cancer and thrombosis, and none of 35 who had not experienced thrombotic problems, was found heterozygous for this mutation. We conclude that the factor V Leiden mutation does not play a significant role in the overall incidence of thromboses that occur in children with cancer.

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To determine the prevalence of activated protein C resistance and the factor V Leiden mutation (position 1691, arginine 506 to glutamine substitution) in children with thrombosis, plasma samples from children with thrombosis were tested for activated protein C resistance. DNA was analyzed for the factor V Leiden mutation. Five of 34 children (15%) had activated protein C resistance; each was heterozygous for the factor V Leiden mutation. All 5 children heterozygous for the factor V Leiden mutation suffered non-CNS venous thromboses comprising 21% of the group of children (5/24) with non-CNS venous thrombotic events. Each of these 5 children had a family history of thrombosis. In conclusion, children with non-CNS venous thrombosis should be evaluated for the factor V Leiden mutation. Children most likely affected are those with a family history of thrombosis.

A factor V506 Arg-Gln mutation is the most common inherited cause of thrombophilia in adults. To date, there are no data regarding the detection of this mutation in neonatal blood or the relationship of this dysfunctional factor V to neonatal thrombosis. This study compared a modified activated protein C resistance functional assay with the PCR-based DNA assay for the factor V mutation in 115 prospectively collected umbilical cord blood samples. The incidence of activated protein C resistance in cord blood was 6%. The sensitivity and specificity of the modified assay for the factor V Leiden mutation was 100%.

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