People with bleeding disorders are unable to form strong blood clots. A person’s blood has different clotting proteins called factors. Each factor plays a different role in the blood clotting process. If a person with a bleeding disorder is unable to form a proper blood clot, their bleeding cannot stop or continues for longer than it should.
Rare factor deficiencies are defined by which type of factor in the blood is low, missing or doesn't work properly. These rare factor deficiencies include factor I (1), II (2), V (5), VII (7), X (10), XI (11), XII (12), and XIII (13). While bleeding disorders are considered rare in the United States, rare factor deficiencies are even less common than other bleeding disorders like hemophilia or von Willebrand disease.
This section on rare factor deficiencies covers the following:
Description: Factor I (1) deficiency describes a group of three rare inherited bleeding disorders caused by a deficiency in fibrinogen. Fibrinogen is a blood protein that helps you form a fibrin mesh around a clot. The mesh keeps the clot firm while healing takes place. With factor I (1) deficiency, your body may make less fibrinogen than it should (Hypofibrinogenemia), no fibrinogen (Afibrinogenemia), or fibrinogen that doesn’t work properly (Dysfibrinogenemia). All three factor I (1) deficiency types are rare. Afibrinogenemia is the least common occurring in only 1 or 2 people per million people.
Symptoms: Afibrinogenemia and hypofibrinogenemia are commonly diagnosed when you are born due to major bleeding from the umbilical cord and circumcision. Other common symptoms include nosebleeds, easy bruising, bleeding in the mouth (for example after dental work), and soft tissue bleeds. Muscle bleeds and joint bleeds can also happen. Women, girls, and those with the potential to menstruate with afibrinogenemia commonly have heavy menstrual bleeding and issues with miscarriage. This is because fibrinogen is necessary for an embryo to attach to the uterus. With dysfibrinogenemia, it may take a long time for your wounds to heal, and you are at risk of blood clots in your veins.
Diagnosis: You may need more than one type of blood test to diagnosis factor I (1) deficiency. These tests include measuring fibrinogen in your blood and the time it takes for your blood to clot during a prothrombin time (PT) test. Diagnosis tests also include an activated partial thromboplastin time (aPTT) test and thrombin clotting time (TCT) test. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor II (2) deficiency is an inherited bleeding disorder caused by a problem with factor II (2), also called prothrombin. In this bleeding disorder, your body is either producing less prothrombin than it should (Hypoprothombinemia) or the prothrombin does not work (Dysprothrombinemia).4 It can also be acquired due to vitamin K deficiency, liver disease, long-term use of antibiotics, bile obstruction or an autoimmune disease. Factor II (2) deficiency affects 1 in 2 million people, and it affects men and women equally.
Symptoms: Symptoms of factor II (2) deficiency differ from person to person. Common symptoms that you may experience include frequent nosebleeds, easy bruising, heavy menstrual bleeding, excessive umbilical cord bleeding, hemorrhaging after surgery or injury, and postpartum hemorrhage.
Diagnosis: Factor II (2) deficiency is diagnosed through blood tests including a prothrombin time (PT) test and an activated partial thromboplastin time (aPTT) test. Levels of prothrombin deficiency can range from 2%-50% of normal levels. Inherited factor II (2) deficiency must be set apart from the acquired form. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor V (5) deficiency is an inherited bleeding disorder where you either do not make enough factor V (5) or the factor V (5) does not work well. The factor V (5) protein in your body speeds up changing prothrombin into thrombin during the beginning of forming a clot. Factor V (5) deficiency affects men and women equally. Fewer than 200 cases have been identified.
Symptoms: If you have factor V (5) deficiency symptoms may include easy bruising, bleeding under the skin, nosebleeds, mouth and gum bleeds, and heavy menstrual bleeding. Severe factor V (5) deficiency can lead to bleeding in the lungs and gastrointestinal tract, which can be life threatening. Babies with severe factor V (5) deficiency have an increased risk of bleeding in their brain.
Diagnosis: Factor V (5) deficiency is diagnosed through blood tests including an activated thromboplastin time (aPTT) test, prothrombin test (PT), and thrombin clotting time test (TCT). A factor V (5) assay, a test that measures factor activity, can confirm diagnosis for you. Platelet function may be affected, too. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Combined factor V (5) and VIII (8) deficiency is an inherited bleeding disorder where the amount of these two factors in your body is lower than normal. It is very rare and found in fewer than 100 people from 60 families worldwide, mostly in Iran, Italy, and Israel. The combined deficiency is different from having factor V (5) deficiency and factor VIII (8) deficiency individually.
Symptoms: Symptoms are generally mild to moderate and include frequent nosebleeds, easy bruising, and excessive bleeding after injury or surgery.
Diagnosis: Combined factor V (5) and factor VIII (8) deficiency is diagnosed by blood tests to determine the levels of these two factors. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor VII (7) deficiency (also known as proconvertin deficiency or Alexander’s Disease) is an inherited disorder. It can also be an acquired disorder due to liver disease, blood cell disorders, certain drugs, or vitamin K deficiency.1 In factor VII (7) deficiency, you have a low amount of factor VII (7) or the factor VII (7) you do have does not work well. It is the most common type of the ultra-rare bleeding disorders. About 1 person per 300,000-500,000 people is diagnosed with factor VII (7) deficiency.
Symptoms: Symptoms of factor VII (7) deficiency can differ from person to person. Your symptoms are not always linked to the level of factor VII (7) in your blood. For example, you may have low factor VII (7) levels but mild symptoms. Symptoms include severe heavy menstrual bleeding and bleeds in the skin, mouth, nose, and the genitourinary tract (which includes the genitals and urinary organs). If you have severe factor VII (7) deficiency you may experience joint and muscle bleeds, easy bruising, and bleeding after surgery. Babies are often diagnosed within the first 6 months of life. Babies may experience a bleed in the central nervous system like a brain bleed, a gastrointestinal tract bleed, or heavy bleeding after circumcision.
Diagnosis: Factor VII (7) deficiency is diagnosed by blood tests including an activated partial thromboplastin time (aPTT) test and a prothrombin time (PT) test. Diagnosis can be confirmed with a factor VII (7) assay, a blood test to measure factor activity. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor X (10) (also known as Stuart-Prower factor) deficiency is an inherited bleeding disorder where your body makes less factor X (10) than it needs, or your factor X (10) does not work well. Factor X (10) turns on enzymes that help you form a blood clot. The factor X (10) protein needs vitamin K, so you can develop factor X (10) deficiency if you have a vitamin K deficiency or liver disease (vitamin K is made by the liver). It can also be acquired if you have amyloidosis (a disease where a protein builds up in your body and affects body functions) or certain cancers. Factor X (10) deficiency affects about 1 in 500,000 people to 1 in a million people and affects men and women equally.
Symptoms: Symptoms of mild factor X (10) deficiency include easy bruising, nose or mouth bleeds, and bleeding after trauma or surgery.2 If you have severe factor X (10) deficiency, symptoms can also include excessive umbilical cord bleeding, joint bleeds, intramuscular bleeds, and a high risk of brain bleeds in the first weeks of life. Women, girls, and those who have the potential to menstruate with factor X (10) deficiency can experience heavy menstrual bleeding. Those who are pregnant may experience a first trimester miscarriage or post-partum hemorrhage.
Diagnosis: Factor X (10) deficiency is diagnosed through family history and by blood tests, including a prothrombin time (PT) test, partial thromboplastin time (PTT) test, or activated partial thromboplastin time (aPTT) test. Diagnosis can be confirmed by a factor X (10) assay, a blood test to measure factor activity. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor XI (11) deficiency (also known as hemophilia C, plasma thromboplastin antecedent deficiency, or Rosenthal syndrome) is an inherited bleeding disorder where your body produces less factor XI (11) than it should, or the factor XI (11) does not work well. Factor XI (11) helps make more of the protein thrombin which is needed to make a fibrin clot. Factor XI (11) deficiency affects about 1 in 100,000 people with about 8% of Ashkenazi Jews in Israel being affected.
Symptoms: Factor XI (11) levels in your blood do not always determine bleeding symptoms. If you have low levels in your blood, you may bleed less than someone with higher levels. Common symptoms can include nosebleeds and soft tissue bleeding, but it is not uncommon for people to discover they have factor XI (11) deficiency after excessive bleeding from a tooth extraction, surgeries, or other traumas. Women, girls, and those who have the potential to menstruate may not realize they have factor XI (11) deficiency until they experience heavy menstrual bleeding or postpartum bleeding.
Diagnosis: Factor XI (11) deficiency is diagnosed by blood tests including a bleeding time test, platelet function tests, a prothrombin time (PT) test, and an activated partial thromboplastin time (aPTT) test. A factor XI (11) assay, a blood test to measure factor activity, helps confirm the diagnosis. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor XII (12) (also known as Hageman factor) deficiency is an inherited bleeding disorder. It affects men and women equally and is more common in Asian people than others. Factor XII (12) helps generate thrombin which you need to make a fibrin clot.
Symptoms: With factor XII (12) deficiency you may experience poor wound healing. Most people, however, do not experience excessive bleeding, even after major surgery.
Diagnosis: Since bleeding time is usually normal with factor XII (12) deficiency, diagnosis is made by a prolonged activated partial thromboplastin time (aPTT) test. A factor XII (12) assay helps confirm the diagnosis. A hematologist at an HTC will order these diagnostic tests and can explain the results to you.
Description: Factor XIII (13) (also known as fibrin stabilizing factor) deficiency is an inherited bleeding disorder where your body either makes less factor XIII (13) than it should, or the factor XIII (13) does not work well. The factor XIII (13) protein stabilizes the formation of a blood clot.3 Without it, a clot can still form but will then break down causing repeated bleeds. Factor XIII (13) deficiency can also be acquired with liver failure, inflammatory bowel disease, and myeloid leukemia. It is the rarest factor deficiency occurring in 1 per 5 million births. It affects men and women equally.
Symptoms: Most people with factor XIII (13) deficiency have symptoms from the time of birth, often bleeding from the umbilical cord (reported in almost 80% of the cases). Up to 30% of those with factor XIII (13) deficiency experience a brain bleed, which is very serious. If you have factor XIII (13) deficiency, your symptoms may include nosebleeds, easy bruising, bleeding in the mouth (for example after dental work), and muscle bleeds. Women, girls, and those who have the potential to menstruate may experience heavy menstrual bleeding and repeat miscarriages. Those with factor XIII (13) deficiency may show signs of infertility.
Diagnosis: Factor XIII (13) deficiency is difficult to diagnose because standard blood clotting tests do not find the deficiency. This is because you can still form a clot with factor XIII (13) deficiency, so clotting tests come back normal. Instead, diagnosis is made using factor XIII (13) assays and a clot solubility test. The high rate of bleeding at birth usually leads to an early diagnosis. A specialized testing laboratory, generally at an HTC, is most often used to complete the tests to confirm factor XIII (13) deficiency.
Finding Resources
The National Hemophilia Foundation has developed several resources for people with rare bleeding disorders, as well as information on lab testing.
If you have a rare factor deficiency, then you have clotting factors in your blood that are missing, low, or not working properly. If you think you may have a rare factor deficiency, it is important to talk with a hematologist, a health care provider who specializes in disorders of the blood. A Hemophilia Treatment Center (HTC) can help you find the right care and treatment to help you thrive.
If you want more information on how treatments for bleeding disorders work, please go to How Do Treatments Work?
1. GARD. (2021, November 8). Factor VII Deficiency | Genetic and Rare Diseases Information Center (GARD). National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/2238/factor-vii-deficiency
2. GARD. (2021, November 8). Factor X Deficiency | Genetic and Rare Diseases Information Center (GARD). National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/6404/factor-x-deficiency
3. GARD. (2021, November 8). Factor XIII Deficiency | Genetic and Rare Diseases Information Center (GARD). National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/10766/factor-xiii-deficiency
4.GARD. (2021, November 8). Prothrombin Deficiency | Genetic and Rare Diseases Information Center (GARD). National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/2926/congenital-factor-ii-deficiency