Thrombosis in otherwise well children with the factor V Leiden mutation☆,☆☆,★,★★

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Abstract

OBJECTIVE: To determine whether resistance to activated protein C caused by the factor V Leiden mutation (Arg506 to Gln) is associated with thrombosis occurring during childhood. STUDY DESIGN: Children with thrombosis were screened for activated protein C resistance. Children found resistant to activated protein C had DNA analysis for the factor V Leiden mutation. Family members of the children with activated protein C resistance were similarly studied. RESULTS: Three of fourteen children examined had abnormal normalized activated protein C sensitivity ratios. One child had protein S deficiency. The children had hyperlipidemia. Molecular confirmation of the factor V Leiden mutation was obtained for all three children. Family members of each of the three children were affected. CONCLUSIONS: Children have thromboses in association with the factor V Leiden mutation, as do adults. This mutation may be identified as an isolated risk factor or in association with other risk factors for thrombosis. (J PEDIATR 1996;128:324-8)

Section snippets

Clinical methods

All children with thrombosis referred to the authors since April 1994 have been screened for APCR. Stored frozen plasma from children seen before April 1994 with thrombosis was also screened after informed consent was obtained. Children with abnormal screening results had molecular confirmation of the factor V Leiden mutation. After recognition of abnormal function by assay, consent was obtained from members of the children's families for functional and molecular studies for the factor V Leiden

Control values

The 22 control children (12 boys) had a mean age of 11 years with a range of 5 to 16 years. Their mean n-APC-SR was 1.22 (SD 0.24) with an observed range of 0.89 to 1.89. Seventy-nine adults (32 women) with a mean age of 38 years (range, 21 to 54 years) composed the adult control group. Their mean n-APC-SR was 1.02 (SD 0.17) and observed range 0.71 to 1.51.

Case reports

Three of fourteen children with thrombosis had an abnormal n-APC-SR and had molecular confirmation of the factor V Leiden mutation.

Patient 1.

DISCUSSION

The protein C system serves a critical role in the regulation of coagulation.16 Recent recognition of the factor V Leiden mutation, which results in resistance of activated factor V to inactivation by activated protein C, has expanded our understanding of this system and familial thrombophilia.17, 18, 19, 20

Our first patient had a family history suggestive of familial thrombophilia, and he had recurrent thrombotic events, including pulmonary emboli. An abnormality predisposing the patient to

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    • Cited by (0)

    ☆

    From the Department of Pediatrics, University of Colorado Health Sciences Center and Children's Hospital, Denver, and Scripps Research Institute, La Jolla, California

    ☆☆

    Supported by grants (Nos. 5 MO1 RR00069 and R37HL52246) from the General Clinical Research Centers Program for the National Center for Research Resources, National Institutes of Health.

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    Reprint requests: Rachelle Nuss, MD, University of Colorado Health Sciences Center, Box C-220, 4200 East Ninth Ave., Denver, CO 80218.

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    0022-3476/96/$5.00 + 0 9/20/70006

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