Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease

Hagstrom, J. Nathan; Walter, Johannes; Bluebond-Langner, Rachel; Amatniek, Joan; Manno, Catherine S.; High, Katherine A.

doi:10.1016/s0022-3476(98)70150-7

Cited by 135 publications

(72 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another important risk factor is inherited thrombophilia as a result of a deficit in antithrombin 9 or proteins C or S, the presence of factor V Leiden, 10 or antiphospholipid syndrome. 11 Inherited thrombotic disorders become manifest in Ͻ5% of affected children.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Aortic Arch Thrombosis as a Result of Congenital Cytomegalovirus Infection

et al. 2001

View full text Add to dashboard Cite

ABSTRACT. Thrombotic disease is rare in neonates. The main risk factors at this age are perinatal asphyxia, maternal diabetes, sepsis, polycythemia, dehydration, a low cardiac output, and in primis the catheterization of central lines. Another important risk factor is inherited thrombophilia. Arterial thrombosis is even more rare than venous thrombosis and less related to most of the risk factors listed above; it occurs more frequently in the iliac, femoral, and cerebral arteries but very rarely in the aorta. Most of the described cases of aortic thrombosis are associated with the catheterization of an umbilical artery and involve the descending tract and the renal arteries; very few relate to the ascending tract and the aortic arch. The possible role of virus-induced primary vascular endothelium damage in the etiopathogenesis of neonatal arterial thrombosis has been previously hypothesized. Herpesviruses, particularly human cytomegalovirus (HCMV), can infect endothelial cells and directly damage intact vascular endothelium, altering its thromboresistant surface as a result of procoagulant activity mediated by specific viral surface phospholipids, necessary for the coagulation enzyme complex assembly that leads to thrombin generation. We describe a case of congenital aortic arch thrombosis. The clinical, laboratory, and virologic pictures; the anatomopathologic findings (fully compatible with viral infection); the detection of HCMV in various tissues (including the aorta); and the absence of other causes of aortic thrombosis make it possible to attribute the case to a severe congenital HCMV infection with multiple organ involvement, after the primary infection of the mother. We describe a case of congenital aortic arch thrombosis in which, on the basis of clinical and virologic findings (and having excluded other thrombosis-favoring conditions), the most likely cause was a severe congenital HCMV infection with multiple organ involvement. The hemostatic system disorders and hemodynamic disturbances related to viral cardiac damage explain the clinical features of the case and indicate that congenital HCMV infection should be included among the causes of neonatal aortic thrombosis. CASE REPORTA female infant was delivered by cesarean section after 37 weeks of gestation because ultrasonography revealed fetal cardiomegaly, cardiac hypertrophy, and pericardial effusion, and it was difficult to image the aorta and aortic flow. Moreover, the pregnancy was complicated by intrauterine growth retardation (IUGR) and oligohydramnios. Genetic amniocentesis performed during the 18th week of gestation revealed a fetal 46XX karyotype. Maternal serologic tests for transmissible infections were performed only during the first trimester of pregnancy; the mother was immune to toxoplasmosis and rubella and negative for HCMV, hepatitis C, hepatitis B, and human immunodeficiency virus; the presence of herpes simplex viruses was not investigated. The pregnancy was uncomplicated until the 30th week, when fetal echography first revealed I...

show abstract

Section: Discussionmentioning

confidence: 99%

Neonatal Aortic Arch Thrombosis as a Result of Congenital Cytomegalovirus Infection

et al. 2001

View full text Add to dashboard Cite

show abstract

“…12,13 Factor V Leiden (FVL) is the most commonly identified risk factor 14 and has been associated with an increased incidence of both spontaneous and catheter-associated thrombosis. 12,[15][16][17] The risk of spontaneous thrombosis increases eightfold in the heterozygous state, and 80-fold in the homozygous state. 18 Prevalence of heterozygous FVL in the North American Caucasian population is 4 to 6%.…”

Section: Introductionmentioning

confidence: 99%

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

et al. 2007

View full text Add to dashboard Cite

Objective: To evaluate the prevalence of hereditary prothrombotic mutations, and their effect on the incidence and severity of umbilical arterial or venous catheter (UAC or UVC)-associated thrombosis.Study Design: All neonates with a UAC or UVC were studied prospectively for the presence, severity and timing of thrombosis with duplex Doppler ultrasound scan. Genetic testing for factor V Leiden (FVL), prothrombin mutation (PTm) and methylene-tetrahydrofolate reductase (MTHFR) mutations was performed using PCR and restriction fragment length polymorphism assays.Result: Umbilical catheter (UC)-associated thrombosis developed in 16/53 (31%) neonates; 23% of UACs and 22% of UVCs were associated with thrombosis. The prevalence of a significant prothrombotic mutation was present in 10/51 (20%) of infants: FVL (8%), MTHFR667 homozygosity (10%), MTHFR1298 homozygosity (2%) and PTm (0%). There was no increase in the risk of UC-associated thrombus in patients carrying these prothrombotic mutations; our study had the power to detect a 2.5-fold increased risk of thrombosis for any of these significant mutations. In addition, MTHFR667 heterozygosity was found in 41% of infants and MTHFR1298 heterozygosity in 52% and also were not associated with increased risk of UC-associated thrombus. The risk of MTHFR double heterozygosity (db het) was 14%, the risk of a significant or db het was 17/51 (33%) and the risk of any mutation was 90%.Conclusion: Prothrombotic genetic mutations are common in our Neonatal Intensive Care Unit population but do not appear to increase the risk of UC-associated thrombosis.

show abstract

“…There are at least three potential independent risk factors for TEs in pediatric patients: the presence of factor V Leiden, prothrombin gene 20210A, and antiphospholipid antibodies (APLAs). [17][18][19][20][21][22][23][24] Factor V Leiden is a mutation in the factor V (FV), which renders FVa resistant to inactivation by activated protein C (APC). 25 FV Leiden is present in 5% of the Caucasian population and in approximately 40% of adults with idiopathic TEs.…”

mentioning

confidence: 99%

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L‐asparaginase

Mitchell

2003

Cancer

250

199

View full text Add to dashboard Cite

show abstract

Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease

Cited by 135 publications

References 26 publications

Neonatal Aortic Arch Thrombosis as a Result of Congenital Cytomegalovirus Infection

Neonatal Aortic Arch Thrombosis as a Result of Congenital Cytomegalovirus Infection

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L‐asparaginase

Contact Info

Product

Resources

About