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Ultra-Rare Factor Deficiencies

Ultra-Rare Factor Deficiencies

When a person has a factor deficiency, they lack or don’t have enough of a clotting factor in their blood to help stop bleeding.

Ultra-rare factor deficiencies certainly live up to their name. They can affect as many as 1 in 500,000 people or as few as 1 in 5 million people. Of all the ultra-rare factor deficiencies combined, there are less than 200,000 reported cases in the U.S.

Very rare factor deficiencies are inherited, you are born with them. Only a few factor deficiencies can be acquired, meaning that they develop during your lifetime.

Common Symptoms of Ultra-Rare Factor Deficiencies

  • Heavy menstrual bleeding (menorrhagia)
  • Easy or unexplained bruising
  • Muscle and soft tissue bleeds
  • Nosebleeds
  • Mouth bleeds
  • Bleeding after surgery or trauma

Types of Ultra-Rare Factor Deficiencies

Factor I (1) Deficiency

Factor I (1) Deficiency is an inherited disorder that affects males and females equally. It is estimated to affect 1-2 in a million people. Fibrinogen helps platelets to stick together to form the initial “plug” after an injury. There are three fibrinogen deficiencies.

  • Afibrinogenemia – no fibrinogen is present
  • Dysfibrinogenemia – fibrinogen doesn’t work correctly
  • Hypofibrinogenemia – not enough fibrinogen is present

Factor I (1) deficiency is often diagnosed in newborns due to excessive bleeding from the umbilical cord or after circumcision. Miscarriage is common in afibrinogenemia. Generally, symptoms are mild, except in afibrinogenemia.

Treatment includes:

  • Factor concentrate for afibrinogenemia and hypofibrinogenemia
  • Fresh frozen plasma or cryoprecipitate for dysfibrinogenemia

Resources: NHF Factor I DeficiencyWorld Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor II (2) Deficiency

Factor II (2) Deficiency is also called Prothrombin Deficiency. It is an inherited disorder that affects males and females equally. Approximately 1 in 2 million people are affected. There are two types of factor II (2) deficiency:

  • Dysprothrombinemia – defect in the structure of prothrombin
  • Hypothrombinemia – not enough prothrombin

At birth, infants may have excessive umbilical cord bleeding. Following childbirth, females may have postpartum hemorrhage. In factor II (2) deficiency, bleeding is usually mild.

Treatment includes prothrombin complex concentrates or fresh frozen plasma.

Resources: NHF Factor II DeficiencyWorld Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor V (5) Deficiency

Factor V (5) deficiency is also called Owren’s disease or parahemophilia. It is an inherited disorder that affects males and females equally. It is estimated to affect 1 in 2 million people.

In severe factor V (5) deficiency, there is a higher risk of bleeding in the brain, lungs, and gastrointestinal tract — all of which can be life-threatening. For most people, the bleeding severity is mild. 

Treatment for factor V (5) deficiency is platelet transfusions or fresh frozen plasma. 

Factor V (5) deficiency is different from Factor V Leiden, which is a clotting disorder.

Resources: Healthline – Factor V Deficiency, NHF Factor V DeficiencyWorld Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor VII (7) Deficiency

Factor VII (7) deficiency is also called Alexander’s disease. It is an inherited disorder that affects males and females equally. Of the ultra-rare factor deficiencies, it is the most common, estimated to affect 1 in 300,000-500,000 people. 

Common symptoms include bleeding into the stomach or intestines. The bleeding severity for factor VII (7) deficiency varies, with severe symptoms with low factor levels.

Treatment for factor VII (7) deficiency includes:

  • Recombinant factor VIIa
  • Prothrombin complex concentrates have been used but both PCCs and FFP have led to thrombosis
  • Fresh frozen plasma

Resources: NORD Factor VII Deficiency, World Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor X (10) Deficiency

Factor X (10) deficiency is also called Stuart-Prower Factor Deficiency. It can be inherited or acquired, meaning it can develop as a result of certain medications or another medical condition. Factor X (10) deficiency affects males and females equally and affects between 1 in 500,000 to 1 in 1 million people.

The most severe bleeding symptom is bleeding into the brain. Bleeding severity in factor X (10) deficiency is moderate to severe with low factor levels.

Treatment:

  • Plasma-derived clotting factor
  • Fresh frozen plasma
  • Antifibrinolytic agents like aminocaproic acid and tranexamic acid
  • Topical therapies

Resources: NHF Factor X DeficiencyNORD – Factor X DeficiencyWorld Federation of Hemophilia, Blood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor XI (11) Deficiency

Factor XI (11) deficiency is also called hemophilia C. It is an inherited disorder that affects males and females equally. It is estimated to affect 1 in 1 million people, but is more common in those of Ashkenazi Jewish descent. In rare cases, factor XI (11) deficiency can be acquired, meaning you are not born with it.

The bleeding severity in factor XII (11) deficiency is usually mild to moderate, even with low factor levels.  Most frequently the bleeding occurs from mucus membranes such as gum bleeding and heavy menses.  

Treatment:

  • Fresh frozen plasma ( in Israel there is a Factor XI plasma product) 
  • Antifibrinolytic agents like aminocaproic acid and tranexamic acid
  • Topical therapies
  • In Europe, there are two factor XI concentrates available. However, neither are available in the U.S.

Resources: NHF Factor XI DeficiencyNORD – Factor XI DeficiencyWorld Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor XII (12) Deficiency

Factor XII (12) deficiency is also called Hageman Factor Deficiency. It is an inherited disorder that affects males and females equally. It is estimated to affect 1 in 1 million people but is more common in people of Asian descent. Patients with inherited FXII deficiency have very long screening blood clotting tests but do not have bleeding. 

Resources: NHF Factor XII DeficiencyNORD – Factor XII DeficiencyBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Factor XIII (13) Deficiency

Factor XII (13) deficiency is an inherited disorder affecting males and females equally. It is the most rare factor deficiency, affecting 1 in 2-5 million people. 

Patients often present with severe bleeding after birth from their belly button when the umbilical cord starts to fall off.  The most common symptom is bleeding into the brain that happens for no reason. Another common symptom is poor wound healing. Miscarriage is common and men can experience signs of infertility. For people with factor XIII (13) deficiency, bleeding severity is severe.

Treatment:

  • Plasma-derived or recombinant factor XIII (13) concentrate

Resource: NHF Factor XIII DeficiencyNORD – Factor XIII DeficiencyWorld Federation of HemophiliaBlood Clotting Factors: Rare Factor Deficiencies | HemAware

Other Rare Bleeding Disorders

Hereditary Hemorrhagic Telangiectasia (HHT)

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu Syndrome, is an inherited disease that leads to malformed blood vessels in multiple organs of the body. The small blood vessels called AVMs are often visible on the inside of the lips and in the nose. Bleeding often begins as nosebleeds during childhood but can progress to bleeding from the intestines or lungs. Both men and women can get this disorder. There is a genetic test to confirm this disorder and treatment consists of a medication that affects new blood vessel growth. 

Resource: Cure HHT