Thrombophilia

• Thrombophilia refers to a group of conditions where the blood clots more easily than normal. This can lead to unwanted blood clots (called thromboses) forming within blood vessels.
• Thrombophilias can be inherited, acquired or mixed.
• Inherited thrombophilias:

  Factor V Leiden

  Prothrombin 20210

  Protein C deficiency

  Protein S deficiency

  Antithrombin deficiency

  Dysfibrinogenaemia

  Combined inherited thrombophilias
• Factor V Leiden:

  Common in people of European origin. It increases the risk of a blood clot in a vein by about eight times. Still a relatively low risk, so most people with factor V Leiden do not develop problems. Some people inherit two genes ('homozygous factor V Leiden'). This makes the risk much higher - eighty times the normal risk.

  This gene affects the factor V part of the clotting cascade. Due to this mutation, protein C, which normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state.
• Prothrombin 20210

  People with the 20210 gene have a change in their prothrombin which makes the blood clot more easily. It is more common in people of South European origin. It increases your risk of having a blood clot to twice the normal risk. This is low risk.

  Causes increased levels of prothrombin causing increased clotting tendencies.
• Protein C deficiency

  The deficiency can be genetic, or due to other conditions such as kidney disease. Risk of developing a clot varies depending on the alteration in protein C gene. If a child inherits two genes with protein C deficiency (one from each parent - this is very rare), they will have a more severe problem. They will get blood clots in the skin soon after birth (a condition called purpura fulminans).

  In protein C deficiency the coagulation cascade continues unchecked with the overactivity of factor V and factor VIII, resulting in excessive thrombin production.
• Protein S deficiency

  Protein S deficiency is rare. The risk of a blood clot forming varies between families.

  In protein S deficiency the coagulation cascade continues unchecked with the overactivity of factor V and factor VIII, resulting in excessive thrombin production.
• Antithrombin deficiency

  Antithrombin deficiency is a fairly severe type of thrombophilia. With this condition, a blood clot can occur not only in the legs or lung but also in the veins of the arms, gut, brain or liver. Long-term warfarin medication.

  Antithrombin inhibits factors 9, 10, 11, 12 and thrombin so when there is a deficiency these factors are activated and cause thrombosis.
• Dysfibrinogenaemia

  This is a rare genetic defect where a clot-dissolving chemical called fibrinogen does not work normally. There may be increased clotting, increased bleeding or both.

  Depending on the fibrinogen abnormality, defects may occur in one or more of the steps in fibrin clot formation.
• Combined inherited thrombophilias

  Some people inherit more than one thrombophilia gene - for example, factor V Leiden plus prothrombin 20210. With combined thrombophilias, the risk of developing a blood clot is multiplied and there is a much greater risk than with either condition alone.

  Dependent on which gene is affected.
• Acquired thrombophilias:

  Antiphospholipid syndrome

  It is caused by antibodies in the blood, which are called antiphospholipid antibodies. APS can cause a blood clot to form in arteries and veins.

  Other acquired conditions

  Other conditions can increase the risk of a blood clot. Some doctors classify these as thrombophilias. Examples are certain disorders affecting platelets, some bone marrow disorders, some kidney problems, inflammatory bowel disease and advanced cancer.
• Hyperhomocysteinaemia

  This is a raised level of a chemical called homocysteine in the blood, which is thought to increase your risk of arterial and venous blood clots. It damages blood vessels. This is a relatively mild condition but it can add to the risk factors for having a blood clot. Vitamin B12 and folic acid may help.
• Paroxysmal nocturnal haemoglobinuria

  This is a rare condition affecting the bone marrow. It can lead to venous blood clots, often in unusual sites such as the veins of the gut, liver or brain.
• Elevated factor VIII

  It is due to abnormally high levels of factor VIII, which is one of the blood chemicals that promotes clotting. Depending on the actual level of factor VIII, it can increase the clotting risk by about six times.

  Interacts with factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.
• Mixed thrombophilias include:

  Hyperhomocysteinaemia

  Paroxysmal nocturnal haemoglobinuria

  Elevated factor VIII
• Testing for thrombophilia:

  Thrombophilia screen

  Antiphospholipid syndrome:

  ·       Antiphospholipid antibodies, Anti-cardiolipin, lupus anticoagulant, or anti β2-glycoprotein I antibodies.

   

  Factor V Leiden

  Protein C and Protein S

  Fibrinogen