Factor V Leiden

Question 1

what is factor V Leiden?

Answer 1

FVL is an abnormal form of factor V caused by a hereditary mutation in the factor V gene

Question 2

what populations if FVL found in?

Answer 2

worldwide

but much more common in Caucasians, particularly those of European ancestry

Question 3

what is the most common hereditary thrombotic disease?

Answer 3

FVL

40-50% of all cases of unexplained thrombosis (that is, thrombosis that happens in the absence of known risk factors like age, smoking, and oral contraceptive use)

Question 4

what does factor V normally do?

Answer 4

participates in coagulation cascade in the communal final pathway

Question 5

what activates factor V?

Answer 5

thrombin

thrombin activates factor V –> Va reaction

Question 6

what is factor Va?

Answer 6

it’s a cofactor in the coagulation cascade

meaning that it acts like an accelerant and really cranks up the production of fibrin

Question 7

how do you turn off the coagulation cascade?

Answer 7

When the time has come to turn off the coagulation cascade, one way to do this is to inhibit factor Va

Question 8

what inhibits Va?

Answer 8

protein C

it grabs on to factor Va and cleaves it, rendering it useless for further involvement in the cascade, causing fibrin formation to dwindle to basically nothing

Question 9

whats the mutation that causes FVL?

Answer 9

factor V Leiden gene contains a single point mutation that results in substitution of glutamine for arginine in the factor V Leiden protein

the problem is that this mutation happens at the place where protein C cleaves and inactivates factor V!!

this means that FVL can participate in the coagulation cascade like normal factor V but when it comes time to stop making fibrin, protein C can’t cleave and inactive FVL

so fibrin continues to be made and the patient runs the risk of getting unwanted clots

arginine –> glutamine

Question 10

What is the mechanism of factor V Leiden?

Answer 10

A mutation in the factor V gene causes resistance to inactivation by activated Protein C

Question 11

what are the clinical manifestos of patients with FVL?

Answer 11

increased clotting risk

Question 12

what factors increase the risk for thrombosis?

Answer 12

• smoking
• old age
• oral contraceptives

Question 13

where do thrombi in patients with FVL occur?

Answer 13

venous system - usually i deep veins of the leg (DVT)

not arterial system

unless there’s something weird like a patent foramen oval or arterial venous fistula, then maybe you could have venous thrombi

Question 14

what should raise suspicion for a possible hereditary thrombotic disorder?

Answer 14

thrombi in weird places like the cerebral, mesenteric, or portal veins

thrombus in a young patient <45

family history of thrombosis

history of previous thrombi

Question 15

how do you diagnose a FVL mutation?

Answer 15

1. analyze genomic DNA from peripheral blood cells

2. aPTT test

Question 16

how does an aPTT test help diagnose FVL?

Answer 16

Normally, when activated protein C is added to an aPTT assay, the clotting time is prolonged by a certain amount

in FVL it’s not prolonged to the same extent

the reduction in prolongation is generally proportional to whether one or two copies of the mutation are present

two tests are run simultaneously; one test is run in the presence of activated protein C (APC), and the other, in the absence. A ratio is determined based on the two tests and the results signify to the laboratory whether APC is working or not

Question 17

how does an FVL mutation effect the time it takes for blood to clot?

Answer 17

it decreases the time it takes for blood to clot

Question 18

what’s the treatment for FVL?

Answer 18

anticoagulation meds

but you have to consider the benefits of anticoagulation vs. risk of bleeding, especially in old people

Question 19

what factors would make you consider a genetic defect?

Answer 19

• young
• no apparent risk factors for
• family history of thrombosis thrombosis

Question 20

aPTT vs. PTT

Answer 20

Partial thromboplastin time (PTT) and activated partial thromboplastin time (aPTT) are used to test for the same functions

however, in aPTT, an activator is added that speeds up the clotting time and results in a narrower reference range

in the case of FVL, activated protein C is added