OOA (Old Order Amish)

Inheritance: autosomal dominant
Genes: F5 F2 PROC

Protein C cofactor
Labile factor
APC cofactor
Activated protein C cofactor
Coagulation factor V
F5

Hemorrhagic disease
Thrombosis
Bleeding disorder
Thrombophilia
Premature births

Factor V Leiden Heterozygosity

Clinical Characteristics

General description (for patients):

This disease can be associated with both excessive bleeding and clotting (thrombosis).  It can be responsible for preterm births as well as an increased risk of blood clots forming in otherwise healthy adults.  The latter may occur in deep veins of the legs as well as in the brain.  Some adults note easy bruising and women may have excessive menstrual bleeding.

Medical description:

A large number of mutations in coagulation factor V glycoprotein have been found.  Disease results in both homozygotes and heterozygotes with a phenotype that is highly variable depending upon the nature of the mutation.  Some mutations result in absence or dysfunction of the activated form leading to hemorrhagic disease, whereas others result in prolonged longevity of this form and are responsible for increased risks of thrombosis. Clinically, factor V heterozygosity can be responsible for excessive preterm births, as well as deep vein and intracranial thromboses.

Genetics:

The F5 gene on chromosome 1 (1q23) encodes the inactive from of the factor V glycoprotein which is activated by thrombin (F2).  It is inactivated by yet another protein product, active protein C (PROC).  F5 is a large gene with 25 exons and the prevalence of mutations in many populations leads to frequent homozygosity and compound heterozygosity with highly variable clinical outcomes.  Factor V heterozygosity occurs in the Amish of Holmes County, Ohio, and is a known cause of premature Amish births in Geauga County, Ohio.

Treatment:

Anticoagulation for thrombosis susceptibility with prolonged therapy beyond the usual time frame.  Stroke victims and pulmonary emboli need not only conventional treatment but careful monitoring of clotting mechanisms.

Prognosis:

Dependent upon susceptibility and nature of risk.  Most patients live long, productive lives.

Ancillary treatments and support:

Tailored to nature of the clotting risks.

Specialists and specialty centers:

Internist, hematologist.

References:

Mann, K.G., and Kalafatis, M.:  Factor V: a combination of Dr Jekyll and Mr Hyde.  Blood 101: 20-30, 2003.  PubMed ID: 12393635

Ridker, P.M., Miletich, J.P., Stampfer, M.J., Goldhaber, S.Z., Lindpaintner, K., and Hennekens, C.H.:  Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.  Circulation 92: 2800-2802, 1995.  PubMed ID: 7586244

Hao, K., Wang, X., Niu, T., Xu, X., Li, A., Chang, W., Wang, L. Li, G., Laird, N., and Xu, X.:  A candidate, gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods. Hum. Molec. Genet. 13: 683-691, 2004.  PubMed ID: 14976157

Resources:

Thrombophilia Awareness Project
NLM Genetics Home Reference
National Hemophilia Foundation

Associated Graphics