What does thrombophilia due to V Leiden mutation mean?
Q: My brother, 22 years old, started sweating in his palms and felt some uneasiness yesterday. We went to the doctor who suggested some tests to him. His reports says: APCR ratio (Activated protein C resistance) is 0.95 L and a normal person should have anywhere between 1.67- 3.75. The doctor says that he may be having thrombophilia, which may be due to factor V Leiden mutation. Can you please explain what this is, why this happens and what can be done?
A:The blood clotting system of the body comprises multiple plasma proteins that interact with platelets (a type of blood cells) to promote physiological coagulation. The formation of a fibrin clot depends on generation of thrombin, which is a key regulator in the haemostatic process. Protein C inhibits thrombin generation by changing into its active form, activated protein C (APC). The condition APC resistance is a resistance to the anticoagulant function of APC, which promotes clotting of blood in the blood vessels (thrombosis). The most common cause of APC resistance (APCR) is a genetic mutation referred to as factor V Leiden. Factor V is a clotting factor whose function is to help blood to clot when an appropriate stimulus is present. It is regulated so that clots don't form too easily or too quickly and this regulation of factor V is done by APC and another substance called Protein S. Activated protein C combines with Protein S to inactivate factor V so that clotting stops. If an individual has the factor V Leiden mutation, there is a change in the structure of factor V and APC/Protein S can no longer inactivate it. This results in resistance to degradation of the activated factor V, thus promoting clotting. This is why factor V Leiden is also (erroneously) known as APC resistance. The condition may be heterozygous (one bad gene but the other factor V gene is normal) or homozygous (both copies of the factor V gene are mutated). The homozygous state results in the entire factor V being resistant to inactivation and such individuals are at higher risk of thrombosis. Thrombosis may also result if factor V is normal but there is deficiency of Protein C or Protein S or there is abnormal Protein C. The APCR assay is not completely specific for factor V Leiden as it may be positive in any condition that affects the activity of APC. In other words, factor V Leiden is characterised by APC resistance but not all APCR is caused by factor V Leiden. There may also be coexistent Protein C deficiency along with factor V Leiden. The assay is not sensitive enough to pick up borderline defect. The condition can be confirmed by a genetic (DNA) test for factor V Leiden, which will pick up the mutation.