8/12/2019 Factorv Leiden

http://slidepdf.com/reader/full/factorv-leiden 1/4

Factor V LeidenFactor V Leiden is a genetically acquired trait that can result in a thrombophilic(hypercoaguable) state resulting in the phenomenon of activated protein C resistance

(APCR) as described below. Associated with factor V Leiden, APCR was first described

in 1993; factor V Leiden was subsequently discovered in 1994. Over 95% of patients

with APCR have factor V Leiden. Factor V Leiden’s overall impact on the coagulationcascade described below.

Mechanism of Action of Factor V Leiden:

Factor V Leiden is characterized by a phenomenon called APCR where a genetic

mutation in the factor V gene causes a change in the factor V protein making it resistant

to inactivation by protein C.

A detailed description of the clotting process is found on the clotting information web

page. The function of protein C is to inactivate factor Va and factor VIIIa (the ‘a’ denotes

the active form). The first step in this process is the activation of thrombomodulin by

thrombin. Subsequently, protein C combines with thrombomodulin in order to produceactivated Protein C (see Figure 1). Activated protein C then combines with protein S on

the surface of a platelet (platelets are the clotting cells that circulate in the blood andprovide phospholipids to support that clotting process). Activated protein C can then

degrade factor Va and factor VIIIa (see Figure 2). When one has factor V Leiden, thefactor Va is resistant to the normal effects of activated protein C, thus the term activated

protein C resistance. The result is that factor V Leiden is not inactivated by activatedprotein C at a much slower rate (see Figure 3), thus leading to a thrombophilic(propensity to clot) state by having increased activity of factor Va in the blood.

8/12/2019 Factorv Leiden

http://slidepdf.com/reader/full/factorv-leiden 2/4

8/12/2019 Factorv Leiden

http://slidepdf.com/reader/full/factorv-leiden 3/4

Factor V Leiden is seen more commonly in the northern European populations. About 4-7% of the general population is heterozygous  for factor V Leiden. About 0.06 to 0.25%

of the population is homozygous  for factor V Leiden. The factor V Leiden mutation isrelatively uncommon in the native populations of Asia, Africa and North America. In

contrast, in Greece and southern Sweden, rates above 10% have been reported.

Risks of Factor V Leiden:

The overall estimated incidence of deep venous thrombosis is 1 episode for every 1000

persons. This figure does not separate patients who had predisposing conditions from

those who do not.

At this time, the data available do not suggest any role between factor V Leiden and

arterial thrombosis (stroke, heart attack).

The role of factor V Leiden and venous thromboembolic disease is shown in the table

below. The table shows the increase in risk compared with a patient without a knownthrombophilic state.

Thrombophilic Status Relative Risk of Venous

Thrombosis

Normal 1

Oral contraceptive (birth control pill) use in apatient with otherwise normal clotting

system

4

Factor V Leiden, heterozygous 5-7

Factor V Leiden,  heterozygous combined

with oral contraceptive use.

30-35

Factor V Leiden, homozygous 80

Factor V Leiden,  homozygous  combined

with oral contraceptive use.

??? >100

Prothrombin Gene Mutation , heterozygous 3

Prothrombin Gene Mutation, homozygous ??? Also possible risk of 

arterial thrombosis

Prothrombin Gene Mutation, heterozygous

combined with oral contraceptive use.16

Protein C deficiency, heterozygous 7

Protein C deficiency, homozygous Severe thrombosis at birth

Protein S deficiency, heterozygous 6Protein S deficiency, homozygous Severe thrombosis at birth

Antithrombin deficiency, heterozygous 5

Antithrombin deficiency, homozygous Thought to be lethal prior tobirth

Hyperhomocysteinemia 2-4

Hyperhomocysteinemia combined with

Factor V Leiden, heterozygous

20

8/12/2019 Factorv Leiden

http://slidepdf.com/reader/full/factorv-leiden 4/4

Treatment of Factor V Leiden:

Treatment of a patient with factor V Leiden depends upon the individual patient’s risk of 

recurrent thromboembolic disease. When one has a venous clot, regardless of whatthrombophilic state(s) one may have, that person will receive anticoagulation. This is

accomplished by several different medications: 1) heparin, 2) warfarin and 3) low-molecular-weight heparins. These medications are generally used for 3-6 months.Further continuation is generally not indicated in factor V Leiden heterozygotes  after a

single thromboembolic episode given the risk of bleeding associated with

anticoagulation. Patients that have had multiple thromboembolic episodes or are at high

risk of further episodes (for example, multiple deficiencies or factor V Leidenhomozygotes) are likely started on long-term anticoagulation.

The use of long-term anticoagulation has risks associated with it (approximately a 3%chance per year of having a major hemorrhage, of which approximately 1/5 are fatal).

Beginning long-term anticoagulation is influenced by the patient’s overall risk of 

recurrent thrombosis balanced against the risks associated with long-term anticoagulationon an individual basis.

Further Information:

For further information on the other thrombophilic states, please refer to their respectivepages. Brief information on the various medications that are discussed above and are

regularly used to treat clotting disorders is discussed on the medication pages. Aselection of the references used to compile this information is listed on the references

page.