Coagulation Factors

Coagulation factor levels are used by health care professionals to determine if the factor is low or absent, associated with reduced clot formation and bleeding, or too high, sometimes associated with too much clot formation and thrombosis. Coagulation factor levels may also be measured to monitor the level during therapy.

Coagulation factor tests may be requested when someone is experiencing excessive bleeding or bruising or has a prolonged Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT). These tests are used as screening tools to determine whether one has a coagulation problem.

Factor testing may be done if an inherited factor deficiency is suspected, especially when bleeding episodes begin early in life or when a close relative has an inherited factor deficiency. If an inherited deficiency is suspected, other family members may also be tested to help confirm the patient’s diagnosis and to establish whether they may be carriers of the condition or have the deficiency themselves (in an asymptomatic or less severe form).

Coagulation factors may be measured when the patient is suspected of having an acquired condition that is causing bleeding, such as vitamin K deficiency or liver disease.

Sometimes factor testing may be done on a patient with a known deficiency to monitor the factor deficiency and to evaluate the effectiveness of treatment.

Normal coagulation factor activity usually means normal clotting function. Low activity of one or more coagulation factors usually means impaired clotting ability. Each coagulation factor must be present in sufficient quantity in order for normal clotting to occur, but the level required is different for each factor. Results are frequently reported as a percentage with 100% being normal. For example, a factor VIII that is 30% would be considered abnormally low.

Deficiencies in coagulation factors may be acquired (due to other diseases) or inherited, mild or severe, permanent or temporary. Those that are inherited are rare and tend to involve only one factor, which may be reduced or absent. Haemophilia A and B are the most common examples of inherited disorders. They are X-linked deficiencies of factors VIII and IX that occur almost exclusively in men (women are usually carriers who are asymptomatic or have mild bleeding). Other inherited factor deficiencies, not associated with the X chromosome, are found equally in both men and women.

The severity of symptoms experienced by a patient with an inherited factor deficiency depends on the factor involved and amount available. Symptoms may vary from episode to episode, from excessive bleeding after dental procedures to severe recurrent bleeding into joints or muscles. Patients with a modest reduction in coagulation factor level may experience few symptoms and may discover their deficiency as an adult - after a surgical procedure or trauma or during screening that includes a Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) test. Those with severe factor deficiencies may have their first bleeding episode very early; for example, a male infant with a deficiency of Factor VIII, IX, or XIII may bleed excessively after circumcision.

Acquired deficiencies may be due to chronic diseases, such as liver disease or cancer; to an acute condition such as disseminated intravascular coagulation (DIC), which uses up clotting factors at a rapid rate; or to a deficiency in vitamin K or treatment with a vitamin K antagonist like warfarin (the production of factors II, VII, IX, and X require vitamin K). If more than one clotting factor is decreased, it is usually due to an acquired condition. Factors may be decreased because of:  

• consumption due to extensive clotting
• liver disease
• some cancers
• severe infections
• exposure to snake venom
• vitamin K deficiency
• anticoagulation therapy
• accidental ingestion of the anticoagulant warfarin or some poisons
• multiple blood transfusions (stored units of blood lose some of their clotting factors)

Elevated levels of several factors are seen in situations of acute illness, stress, or inflammation. Some patients have persistent elevations of factor VIII that may be associated with an increased risk of venous thrombosis.

For both inherited and acquired factor deficiencies, the missing factor(s), once identified, can be replaced as needed. This may be done with a transfusion of fresh frozen plasma (FFP), which contains all of the missing factors, with a concentrated cryoprecipitate, with replacement factors (available commercially either recombinant factor predominantly used in children or plasma derived factors), or with desmopressin (DDAVP) - a drug that stimulates the body to release more factor VIII. These treatments may be used during a bleeding episode or to prevent excessive bleeding during an upcoming surgery or dental procedure.

von Willebrand factor is responsible for helping platelets stick to the injured blood vessel wall. A blood clot then occurs around platelets at the site of injury. A deficiency or abnormality in von Willebrand factor can cause von Willebrand disease, an inherited bleeding disorder. It is associated with a secondary decrease in factor VIII concentration, as von Willebrand factor also binds to and stabilizes factor VIII in the blood stream. While von Willebrand factor may be used with coagulation factors if an inherited factor deficiency is suspected, it is usually considered separately because it is associated with platelets and not part of the classic coagulation cascade.