Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: A prospective study,☆☆

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Abstract

Objective: To determine the association between catheter-related thromboses and hereditary causes of thrombophilia, including the factor V Leiden mutation, deficiencies of protein C or protein S, or increased lipoprotein (a).

Study design: To evaluate the incidence of genetic risk factors for familial thrombophilia in catheter-related thrombosis, 163 consecutively admitted infants and children (cardiac disease and catheter placement [C] n = 140; Broviac catheter [B] n = 23) were prospectively investigated. In addition, an age-matched, healthy control group undergoing elective surgery (S: n = 155) was investigated.

Results: Heterozygous factor V Leiden mutation was diagnosed in 20 of the 318 study subjects (C: n = 5; B: n = 4; S: n = 11), homozygous factor V Leiden mutation was found in two subjects (C: n = 1; S: n = 1), protein C deficiency type I was diagnosed in nine subjects (C: n = 4; B: n = 1; S: n = 4), and five subjects showed increased lipoprotein (a) (C: n = 3; S: n = 2). The frequency of thrombosis (C: n = 13; B: n = 5) in patients with familial thrombophilia was significantly higher ( p < 0.0001; chi square: 27.79) in the catheter groups (15 of 17 subjects) than in control subjects after minor elective surgery (none of 18). Fifteen of the 18 infants with thrombosis had congenital thrombophilia; two children with congenital thrombophilia did not have documented thrombosis, and three infants with vascular occlusion had no inherited predisposition to thrombophilia.

Conclusions: Genetic risk factors for familial thrombophilia play an important role in the manifestation of catheter-related thromboembolism in children. (J Pediatr 1997;131:608-12)

Section snippets

Methods

Over a 2-year period, 163 consecutively admitted infants and children, ranging in age from neonate to 18 years, were enrolled in the study. In addition, to compare the prevalence of familial thrombophilia, 155 age-matched, healthy children undergoing elective minor surgery (S) were investigated in the same fashion.

One hundred forty children (C) without previously diagnosed thromboembolism underwent diagnostic percutaneous venous cardiac catheterization, and in 105 of these 140 children, central

Results

No difference was seen in the prevalence of familial thrombophilia in the two age-matched populations studied: heterozygous factor V Leiden mutation was diagnosed in 20 of the 318 subjects (C: n = 5; B: n = 4; S: n = 11), homozygous factor V Leiden mutation was found in two subjects (C: n = 1; S: n = 1), protein C deficiency type I was diagnosed in nine subjects (C: n = 4; B: n = 1; S: n = 4), and five of the 318 subjects showed increased plasma concentrations of Lp (a) (C: n = 3; S: n = 2).

Discussion

Data from this prospective study demonstrate, both clinically and sonographically, 8, 9, 12 an 11% overall incidence of catheter-related thrombus formation in children with indwelling central lines, which was in most cases associated with genetic risk factors for familial thrombophilia. The factor V Leiden mutation, also stated to be a genetic risk factor for childhood thromboembolism, 15, 21, 22, 23 plays the major role in catheter-related thrombosis in the population studied. Deficiencies of

Acknowledgements

We thank Susan Griesbach for editing this manuscript.

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    Reprint requests: Ulrike Nowak-Göttl, MD, Westfälische Wilhelms-Universität, Pediatric Hematology and Oncology, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany.

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