Prothrombin deficiency

Other Names: Hypoprothrombinemia, inherited; Congenital factor II deficiency; Dysprothrombinemia; Inherited prothrombin deficiency; Inherited hypoprothrombinemia; Factor II deficiency Prothrombin (or factor II) deficiency is a blood disorder that affects the ability of the blood to clot properly. Prothrombin deficiency is a disorder caused by a lack of a protein in the blood called prothrombin.

Types

There are two types of inherited prothrombin deficiency. Type I or hypoprothrombinemia and type II or dysprothrombinemia.

Cause

Prothrombin deficiency can be caused by changes (mutations) in the F2 gene. The F2 gene provides instructions to the body to make a protein called prothrombin. Prothrombin helps the body make blood clots in response to injury. One step of the process involves prothrombin binding to platelets, which helps the body form clots. When there are disease causing changes to the F2 gene, not enough working prothrombin protein is made, so the body cannot form clots properly. There are two types of inherited prothrombin deficiency, type I and type II.

Type I or hypoprothrombinemia is more severe, and it is characterized by a decreased level of normally functioning protein, and therefore, by a decrease in proteinactivity. Type II or dysprothrombinemia is characterized by normal or low-normal levels of an abnormal (dysfunctional) protein. Bleeding symptoms vary depending on the amount of residual functional activity.

Inheritance

Autosomal recessive inheritance, a 25% chance

When prothrombin deficiency is caused by genetic changes (mutations) to the F2 gene, it is inherited in an autosomal recessive manner. This means that both copies of the F2 gene must be changed in order for a person to have symptoms of the disease. We inherit one copy of each gene from our mother and the other one from our father. Men and women with a disease-causing change in only one copy of the F2 gene are known as carriers of prothrombin deficiency (or factor II deficiency). When two carriers have children together, for each child there is a: 25% chance that the child will have prothrombin deficiency 50% chance that the child will be a carrier of prothrombin deficiency like the parents 25% chance that the child will have two working copies of the F2 gene, so the child will not have prothrombin deficiency and will not be a carrier Carriers of prothrombin (factor II) deficiency typically do not show severe signs and symptoms of the disease, but some may have increased bleeding after surgery.

When prothrombin (factor II) deficiency is acquired, it is not caused by genetic changes in the F2 gene. In these cases, the disease typically does not run in families, unless the underlying cause of the associated disease is also passed from parents to children.

Signs and symptoms

Symptoms of the deficiency include prolonged bleeding, especially after an injury or after surgery. Women with prothrombin deficiency may have heavy menstrual bleeding. The severity of the disease can vary, with some people experiencing severe bleeding without any known cause, and others only experiencing increased bleeding after a surgery or serious injury.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Prolonged partial thromboplastin time
• Prolonged prothrombin time
• Reduced prothrombin antigen

30%-79% of people have these symptoms

• Epistaxis(Bloody nose)
• Intracranial hemorrhage(Bleeding within the skull)
• Joint hemorrhage(Bleeding within a joint)

5%-29% of people have these symptoms

• Abnormal umbilical stump bleeding
• Anemia(Low number of red blood cells or hemoglobin)
• Cephalohematoma
• Excessive bleeding from superficial cuts
• Intramuscular hematoma
• Menorrhagia(Abnormally heavy bleeding during menstruation)
• Microscopic hematuria(Small amount of blood in urine)
• Oral cavity bleeding(Bleeding from mouth)
• Post-partum hemorrhage(Bleeding post-delivery)
• Prolonged bleeding after dental extraction
• Prolonged bleeding following circumcision

Diagnosis

Tests that may be done include:

• Factor II assay
• Partial thromboplastin time
• Prothrombin time (PT)
• Mixing study (a special PTT test to confirm prothrombin deficiency)

Treatment

The treatment of prothrombin deficiency depends on the exact cause and severity of the disease. When a person with prothrombin (factor II) deficiency has bleeding episodes, fresh frozen plasma, the part of the blood that contains the clotting factors, can be used to treat the bleeding. If a person with prothrombin deficiency requires surgery, plasma exchange therapy may be used to increase factor II (prothrombin) levels prior to surgery.

People who have acquired prothrombin deficiency may benefit from taking vitamin K. Some people with prothrombin deficiency may be recommended to avoid activities that can result in physical contact or injuries. In some cases, prothrombin complex concentrates can be used to increase factor II levels. However, because these concentrates contain clotting factors other than factor II, they can result in an increased risk for blood to clot too quickly within the blood vessels (thromboembolic event).

Prognosis

The outcome is good with proper treatment. Inherited prothrombin deficiency is a lifelong condition. The outlook for acquired prothrombin deficiency depends on the cause. If it is caused by liver disease, the outcome depends on how well your liver disease can be treated. Taking vitamin K supplements will treat vitamin K deficiency.

Possible Complications Severe bleeding in the organs can occur.

Prevention

There is no known prevention for inherited prothrombin deficiency. When a lack of vitamin K is the cause, using vitamin K can help.

NIH genetic and rare disease info

• NIH info on Prothrombin deficiency

Prothrombin deficiency is a rare disease.

Prothrombin deficiency Resources
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