Types of Rare Bleeding Disorders

Factor I (Fibrinogen) Deficiency
Factor I (also called fibrinogen) deficiency is an inherited bleeding disorder that is caused by a problem with factor I. Because the body produces less fibrinogen than it should, or because the fibrinogen is not working properly, the clotting reaction is blocked prematurely, and the blood clot does not form.
Factor I deficiency is an umbrella term for several related disorders known as congenital fibrinogen defects. Afibrinogenemia (a complete lack of fibrinogen) and hypofibrinogenemia (low levels of fibrinogen) are quantitative defects, meaning the amount of fibrinogen in the blood is abnormal. Dysfibrinogenemia is a qualitative defect in which fibrinogen does not work the way it should. Hypodysfibrinogenemia is a combined defect that involves both low levels of fibrinogen and impaired function.
Afibrinogenemia is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. Like all autosomal recessive disorders, afibrinogenemia is found more frequently in areas of the world where marriage between close relatives is common. Hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia can be either recessive (both parents carry the gene) or dominant (only one parent carries and transmits the gene). All types of factor I deficiency affect both males and females.

What are the symptoms?
The symptoms of factor I deficiency differ depending on which form of the disorder a person has.
AFIBRINOGENEMIA
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• heavy or prolonged menstrual bleeding (menorrhagia)
• muscle bleeds
• bleeding into joints (hemarthrosis)
• bleeding from the umbilical cord stump at birth
• bleeding in the mouth, particularly after dental surgery or tooth extraction
• abnormal bleeding during or after injury, surgery, or childbirth
• abnormal bleeding after circumcision
• problems during pregnancy (including miscarriage)
Other reported symptoms
• bleeding in the gut (gastrointestinal haemorrhage)
• bleeding in the central nervous system (the brain and spinal cord)
• formation of blood clots (thrombosis)
HYPOFIBRINOGENEMIA
Symptoms are similar to those seen in afibrinogenemia. As a general rule, the less factor I a person has in his/her blood, the more frequent and/or severe the symptoms.
DYSFIBRINOGENEMIA
Symptoms depend on how the fibrinogen (which is present in normal quantities) is functioning. Some people have no symptoms at all. Other people experience bleeding (similar to those seen in afibrinogenemia) and others show signs of thrombosis (abnormal blood clots in blood vessels) instead of bleeding.
HYPODYSFIBRINOGENEMIA
Symptoms are variable and depend on the amount of fibrinogen that is produced and how it is functioning.
How is it diagnosed?
Factor I deficiency is diagnosed by a variety of blood tests, including a specific test that measures the amount of fibrinogen in the blood. However, low fibrinogen levels or abnormal function may be a sign of another disease, such as liver or kidney disorders, which should be ruled out before a bleeding disorder is diagnosed. Diagnostic tests should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are three treatments available for factor I deficiency. All are made from human plasma.
• Fibrinogen concentrate
• Cryoprecipitate
• Fresh frozen plasma (FFP)
Treatment may also be given to prevent the formation of blood clots, as this complication can occur after fibrinogen replacement therapy.
Many people who have hypofibrinogenemia or dysfibrinogenemia do not need treatment. Excessive menstrual bleeding in women with factor I deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Factor II (Prothrombin) Deficiency
Factor II (also called prothrombin) deficiency is an inherited bleeding disorder that is caused by a problem with factor II. Because the body produces less prothrombin than it should, or because the prothrombin is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor II deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. Factor II deficiency is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
Factor II deficiency may be inherited with other factors deficiencies (see “Combined deficiency of vitamin K-dependent clotting factors”). It can also be acquired later in life as a result of liver disease, vitamin K deficiency, or certain medications such as the blood-thinning drug Coumadin®. Acquired factor II deficiency is more common than the inherited form.
What are the symptoms?
The symptoms of factor II deficiency are different for everyone. As a general rule, the less factor II a person has in his/her blood, the more frequent and/or severe the symptoms.
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• heavy or prolonged menstrual bleeding (menorrhagia)
• bleeding into joints (hemarthrosis)
• muscle bleeds
• bleeding in the mouth, particularly after dental surgery or tooth extraction
Other reported symptoms
• bleeding in the gut (gastrointestinal haemorrhage)
• bleeding from the umbilical cord stump at birth
• abnormal bleeding during or after injury, surgery, or childbirth
Rare symptoms
• bleeding in the central nervous system (the brain and spinal cord)
• blood in urine (hematuria)
How is it diagnosed?
Factor II deficiency is diagnosed by a variety of blood tests. The doctor will need to measure the amount of factors II, V, VII, and X in the blood. Diagnostic tests should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are two treatments available for factor II deficiency. Both are made from human plasma.
Prothrombin complex concentrate (PCC)
Fresh frozen plasma (FFP)
Excessive menstrual bleeding in women with factor II deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Factor V Deficiency
Factor V deficiency is an inherited bleeding disorder that is caused by a problem with factor V. Because the body produces less factor V than it should, or because the factor V is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor V deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. Factor V deficiency is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
What are the symptoms?
The symptoms of factor V deficiency are generally mild. Some people may experience no symptoms at all. However, children with a severe deficiency of factor V may bleed very early. Some patients have experienced bleeding in the central nervous system (the brain and spinal cord) very early in life.
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• heavy or prolonged menstrual bleeding (menorrhagia)
• bleeding in the mouth, particularly after dental surgery or tooth extraction
Other reported symptoms
• bleeding in the gut (gastrointestinal haemorrhage)
• muscle bleeds
• abnormal bleeding during or after injury, surgery, or childbirth
Rare symptoms
• bleeding into joints (hemarthrosis)
• bleeding in the central nervous system (the brain and spinal cord)
How is it diagnosed?
Factor V deficiency is diagnosed by a variety of blood tests that should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre. People with abnormal levels of factor V should also have their factor VIII levels checked to rule out combined factor V and factor VIII deficiency, which is a completely separate disorder.
How is it treated?
Treatment for factor V deficiency is usually only needed for severe bleeds or before surgery. Fresh frozen plasma (FFP) is the usual treatment because there is no concentrate containing only factor V. Platelet transfusions, which contain factor V, are also sometimes an option.
Excessive menstrual bleeding in women with factor V deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS
Combined Factor V and Factor VIII Deficiency
Combined factor V and factor VIII deficiency is an inherited bleeding disorder that is caused by low levels of factors V and VIII. Because the amount of these factors in the body is lower than normal, the clotting reaction is blocked prematurely and the blood clot does not form. The combined deficiency is completely separate from factor V deficiency and factor VIII deficiency (Haemophilia A).
Combined factor V and factor VIII deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. The deficiency is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common. Most cases are found around the Mediterranean Sea, especially in Israel, Iran, and Italy.
Normally the disorder is caused by a single gene defect that affects the body’s ability to transport factor V and factor VIII outside the cell and into the bloodstream, and not by a problem with the gene for either factor.
What are the symptoms?
The combination of factor V and factor VIII deficiency does not seem to cause more bleeding than if only one or the other of the factors were affected. The symptoms of combined factor V and factor VIII deficiency are generally mild.
Common symptoms
• skin bleeding
• heavy or prolonged menstrual bleeding (menorrhagia)
• bleeding in the mouth, particularly after dental surgery or tooth extraction
• bleeding after circumcision
• abnormal bleeding during or after injury, surgery, or childbirth
Other reported symptoms:
• nosebleeds (epistaxis)
Rare symptoms
• bleeding into joints (hemarthrosis)
• muscle bleeds
How is it diagnosed?
Combined factor V and factor VIII deficiency is diagnosed by a variety of blood tests to determine if the levels of both factors are lower than normal. These tests should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are three treatments available for combined factor V and factor VIII deficiency.
• Factor VIII concentrate
• Fresh frozen plasma (FFP)
• Desmopressin
Excessive menstrual bleeding in women with combined factor V and factor VIII deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Factor VII Deficiency
Factor VII deficiency is an inherited bleeding disorder that is caused by a problem with factor VII. Because the body produces less factor VII than it should, or because the factor VII is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor VII deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. Factor VII deficiency is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
Factor VII deficiency may be inherited with other factor deficiencies (see “Combined deficiency of vitamin K-dependent clotting factors”). It can also be acquired later in life as a result of liver disease, vitamin K deficiency, or certain medications such as the blood-thinning drug Coumadin®.
What are the symptoms?
The symptoms of factor VII deficiency are different for everyone. As a general rule, the less factor VII a person has in his/her blood, the more frequent and/or severe the symptoms. People with very low levels of factor VII can have very serious symptoms.
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• heavy or prolonged menstrual bleeding (menorrhagia)
• bleeding in the mouth, particularly after dental surgery or tooth extraction
• bleeding in the head (newborns)
• heavy bleeding at circumcision
Other reported symptoms
• bleeding in the gut (gastrointestinal bleeding)
• bleeding into joints (hemarthrosis)
• muscle bleeds
• bleeding in the central nervous system (the brain and spinal cord)
• abnormal bleeding during or after injury, surgery, or childbirth
Rare symptoms
• blood in urine (hematuria)
• bleeding from the umbilical cord stump at birth
How is it diagnosed?
Factor VII deficiency is diagnosed by a variety of blood tests that should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are several treatments available for factor VII deficiency.
• Recombinant factor VIIa concentrates (rFVIIa)
• Factor VII concentrate
• Prothrombin complex concentrate (PCC) containing factor VII
• Fresh frozen plasma (FFP)
• Excessive menstrual bleeding in women with factor VII deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Factor X Deficiency
Factor X deficiency is an inherited bleeding disorder that is caused by a problem with factor X. Because the body produces less factor X than it should, or because the factor X is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor X deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. Factor X deficiency is one of the rarest inherited clotting disorders, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
Factor X deficiency may also be inherited with other factor deficiencies (see “Combined deficiency of vitamin K-dependent clotting factors”).
What are the symptoms?
As a general rule, the less factor X a person has in his/her blood, the more frequent and/or severe the symptoms. People with severe factor X deficiency can have serious bleeding episodes.
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• bleeding in the gut (gastrointestinal haemorrhage)
• bleeding into joints (hemarthrosis)
• muscle bleeds
• bleeding from the umbilical cord stump at birth
• bleeding from the mouth, particularly after dental surgery or tooth extraction
• bleeding during or after surgery or injury
Other reported symptoms
• heavy or prolonged menstrual bleeding (menorrhagia)
• bleeding after circumcision
• abnormal or prolonged bleeding after childbirth
• first-trimester miscarriage (spontaneous abortion)
• blood in urine (hematuria)
• bleeding in the central nervous system (the brain and spinal cord)
How is it diagnosed?
Factor X deficiency is diagnosed by a variety of blood tests that should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are two treatments available for factor X deficiency. Both are made from human plasma.
• Factor X Concentrate
• Prothrombin complex concentrate (PCC) containing factor X
• Fresh frozen plasma (FFP)
• Excessive menstrual bleeding in women with factor X deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Combined Deficiency of Vitamin K- Dependent Clotting Factors
Inherited combined deficiency of the vitamin K-dependent clotting factors (VKCFD) is a very rare inherited bleeding disorder that is caused by a problem with clotting factors II, VII, IX, and X. In order to continue the chain reaction of the coagulation cascade, these four factors need to be activated in a chemical reaction that involves vitamin K. When this reaction does not happen the way it should, the clotting reaction is blocked and the blood clot does not form.
VKCFD is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. VKCFD is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
VKCFD can also be acquired later in life as a result of disorders of the bowel, liver disease, dietary vitamin K deficiency, or certain medications such as the blood-thinning drug Coumadin®. Acquired VKCFD is more common than the inherited form. Some newborn babies have a temporary vitamin K deficiency, which can be treated with supplements at birth.
What are the symptoms?
The symptoms of VKCFD vary a great deal from one individual to another but are generally mild. The first symptoms may appear at birth or not until later in life. Symptoms at birth must be differentiated from the acquired deficiency. People with severe deficiencies can have serious bleeding episodes, but the more serious symptoms are generally rare and only occur in those individuals with very low factor levels.
Reported symptoms
• bleeding from the umbilical cord stump at birth
• bleeding into joints (hemarthrosis)
• bleeding in soft tissue and muscle
• bleeding in the gut (gastrointestinal haemorrhage)
• easy bruising
• excessive bleeding after surgery
Rare symptoms
• bleeding in the brain (intracranial haemorrhage)
• skeletal abnormalities and mild hearing loss (in severe cases)
How is it diagnosed?
VKCFD is diagnosed by a variety of blood tests that should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre. Care should be taken, particularly in newborns, to exclude causes of acquired vitamin K deficiency or exposure to certain medications.
How is it treated?
There are three treatments available for VKCFD.
• Vitamin K
• Prothrombin complex concentrates (PCC)
• Fresh frozen plasma (FFP)
• For more information on TREATMENT OPTIONS

Factor XI Deficiency
Factor XI deficiency is an inherited bleeding disorder that is caused by a problem with factor XI. Because the body produces less factor XI than it should, or because the factor XI is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor XI deficiency is also called Haemophilia C. It differs from Haemophilia A and B in that there is no bleeding into joints and muscles. Factor XI deficiency is the most common of the rare bleeding disorders and the second most common bleeding disorder affecting women (after von Willebrand disease).
Some people have inherited factor XI deficiency when only one parent carries the gene. The disorder is most common in Ashkenazi Jews, that is, Jews of Eastern European ancestry.
What are the symptoms?
Most people with factor XI deficiency will have little or no symptoms at all. The relationship between the amount of factor XI in a person’s blood and the severity of his/her symptoms is unclear; people with only a mild deficiency in factor XI can have serious bleeding episodes. Symptoms of factor XI deficiency vary widely, even among family members, which can make it difficult to diagnose.
Common symptoms
• nosebleeds (epistaxis)
• easy bruising
• heavy or prolonged menstrual bleeding (menorrhagia)
• abnormal bleeding during or after injury, surgery, or childbirth
Other reported symptoms
• bleeding in the gut (gastrointestinal haemorrhage)
• bleeding in the mouth, particularly after dental surgery or tooth extraction
• blood in the urine (hematuria)

How is it diagnosed?
Factor XI deficiency is diagnosed by a variety of blood tests that should be performed by a specialist at a Haemophilia/bleeding disorders treatment centre.
How is it treated?
There are several treatments available to help control bleeding in people with factor XI deficiency.
• Factor XI concentrate
• Antifibrinolytic drugs
• Fibrin glue
• Fresh frozen plasma (FFP)
• Excessive menstrual bleeding in women with factor XI deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS

Factor XIII Deficiency
Factor XIII deficiency is an inherited bleeding disorder that is caused by a problem with factor XIII. Because the body produces less factor XIII than it should, or because the factor XIII is not working properly, the clotting reaction is blocked prematurely and the blood clot does not form.
Factor XIII deficiency is an autosomal recessive disorder, which means that both parents must carry the defective gene in order to pass it on to their child. It also means that the disorder affects both males and females. Factor XIII deficiency is very rare, but like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common.
What are the symptoms?
Most people with factor XIII deficiency experience symptoms from birth, often bleeding from the umbilical cord stump. Symptoms tend to continue throughout life. As a general rule, the less factor XIII a person has in his/her blood, the more frequent and/or severe the symptoms.
Common symptoms
• bleeding from the umbilical cord stump at birth
• nosebleeds (epistaxis)
• easy bruising
• bleeding into joints (hemarthrosis)
• bleeding in the central nervous system (the brain and spinal cord)
• bleeding in the mouth, particularly after dental surgery or tooth extraction
• poor wound healing and abnormal scar formation
• bleeding in soft tissue
• problems during pregnancy (including recurrent miscarriages)
• bleeding after circumcision
• abnormal bleeding during or after injury or surgery
Other reported symptoms
• heavy or prolonged menstrual bleeding (menorrhagia)
• blood in urine (hematuria)
• bleeding in the gut (gastrointestinal hemorrhage)
• muscle bleeds
Rare symptoms
• bleeding in the spleen, lungs, ears, or eyes
How is it diagnosed?
Factor XIII deficiency is difficult to diagnose. Standard blood clotting tests do not detect the deficiency, and many laboratories are not equipped with more specialized tests that measure the amount of factor XIII in a blood sample or how well factor XIII is working. The high rate of bleeding at birth usually leads to early diagnosis.
How is it treated?
There are several treatments available to help control bleeding in people with factor XIII deficiency.
• Factor XIII concentrate
• Cryoprecipitate
• Fresh frozen plasma (FFP)
• Excessive menstrual bleeding in women with factor XIII deficiency may be controlled with hormonal contraceptives (birth control pills) or antifibrinolytic drugs.
For more information on TREATMENT OPTIONS