Types of Bleeding Disorders

Although there are many different types of bleeding disorders, here you will find information on hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease, and rare factor deficiencies including I, II, V, VII, X, XI, XII and XIII.

Hemophilia A

Hemophilia A, also called factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a change in a gene.

According to the US Centers for Disease Control and Prevention, hemophilia occurs in approximately 1 in 5,000 live births. There are about 20,000 people with hemophilia in the US. All races and ethnic groups are affected. Hemophilia A is four times as common as hemophilia B while more than half of patients with hemophilia A have the severe form of hemophilia.

Genetics

The X and Y chromosomes are called sex chromosomes. The gene for hemophilia is carried on the X chromosome. Hemophilia is inherited in an X-linked recessive manner.  Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). That means if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. It also means that fathers cannot pass hemophilia on to their sons.

But because daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, most likely they will inherit a healthy X chromosome from their father and not have hemophilia. A daughter who inherits an X chromosome that contains the gene for hemophilia is called a carrier. She can pass the gene on to her children. Hemophilia can occur in daughters, but is rare.

For a female carrier, there are four possible outcomes for each pregnancy:

  1. A girl who is not a carrier
  2. A girl who is a carrier
  3. A boy without hemophilia
  4. A boy with hemophilia

Severity

(percentage breakdown of overall hemophilia population by severity)

  • Severe (factor levels less than 1%) represent approximately 60% of cases
  • Moderate (factor levels of 1-5%) represent approximately 15% of cases
  • Mild (factor levels of 6%-30%) represent approximately 25% of cases

Symptoms

People with hemophilia A often bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures or trauma. How frequently a person bleeds and the severity of those bleeds depends on how much FVIII is in the plasma, the straw-colored fluid portion of blood.

Normal plasma levels of FVIII range from 50% to 150%. Levels below 50%, or half of what is needed to form a clot, determine a person’s symptoms.

  • Mild hemophilia A- 6% up to 49% of FVIII in the blood. People with mild hemophilia generally experience bleeding only after serious injury, trauma or surgery. In many cases, mild hemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild hemophilia often experience menorrhagia, heavy menstrual periods, and can hemorrhage after childbirth.
  • Moderate hemophilia A. 1% up to 5% of FVIII in the blood. People with moderate hemophilia A tend to have bleeding episodes after injuries. Bleeds that occur without obvious cause are called spontaneous bleeding episodes.
  • Severe hemophilia A. <1% of FVIII in the blood. People with severe hemophilia A experience bleeding following an injury and may have frequent spontaneous bleeding episodes, often into their joints and muscles.

Diagnosis

The best place for patients with hemophilia to be diagnosed and treated is at one of the federally-funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers.

A medical health history is important to help determine if other relatives have been diagnosed with a bleeding disorder or have experienced symptoms. Tests that evaluate clotting time and a patient’s ability to form a clot may be ordered. A clotting factor test, called an assay, will determine the type of hemophilia and its severity.

Treatment

The main medication to treat hemophilia A is concentrated FVIII product, called clotting factor or simply factor. Recombinant factor products, which are are developed in a lab through the use of DNA technology, , preclude the use of human-derived pools of donor-sourced plasma. And while plasma-derived FVIII  products are still available, approximately 75% of the hemophilia community takes a recombinant FVIII product.

These factor therapies are infused intravenously through a vein in the arm or a port in the chest. The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation encourages the use of recombinant clotting factor products because they are safer. Your doctor or your HTC will help you decide which is right for you.

Patients with severe hemophilia may be on a routine treatment regimen, called prophylaxis, to maintain enough clotting factor in their bloodstream to prevent bleeds. MASAC recommends prophylaxis as optimal therapy for children with severe hemophilia A.

DDAVP (desmopressin acetate) is the synthetic version of vasopressin, a natural antidiuretic hormone that helps stop bleeding. In patients with mild hemophilia, it can be used for joint and muscle bleeds, for bleeding in the mucous membranes of the nose and mouth, and before and after surgery. It comes in an injectable form and a nasal spray.

Aminocaproic acid prevents the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds. It is taken orally, as a tablet or liquid. MASAC recommends that a dose of clotting factor be taken first to form a clot, then aminocaproic acid, to preserve the clot and keep it from being broken down prematurely.

Source: Adapted from National Hemophilia Foundation

Hemophilia B

Hemophilia B, also called factor IX (FIX) deficiency or Christmas disease, is a genetic disorder caused by missing or defective factor IX, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a change in a gene.

According to the US Centers for Disease Control and Prevention, hemophilia occurs in approximately 1 in 5,000 live births. There are about 20,000 people with hemophilia in the US. All races and ethnic groups are affected. Hemophilia B is four times less common than hemophilia A.

Genetics

The X and Y chromosomes are called sex chromosomes. The gene for hemophilia is carried on the X chromosome. Hemophilia is inherited in an X-linked recessive manner.  Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). That means if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. It also means that fathers cannot pass hemophilia on to their sons.

 

But because daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, most likely they will inherit a healthy X chromosome from their father and not have hemophilia. A daughter who inherits an X chromosome that contains the gene for hemophilia is called a carrier. She can pass the gene on to her children. Hemophilia can occur in daughters, but is rare.

For a female carrier, there are four possible outcomes for each pregnancy:

  1. A girl who is not a carrier
  2. A girl who is a carrier
  3. A boy without hemophilia
  4. A boy with hemophilia

Severity

(percentage breakdown of overall hemophilia population by severity)

  • Severe (factor levels less than 1%) represent approximately 60% of cases
  • Moderate (factor levels of 1-5%) represent approximately 15% of cases
  • Mild (factor levels of 6%-30%) represent approximately 25% of cases

Symptoms

People with hemophilia B bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures or trauma. How frequently a person bleeds and how serious the bleeds are depends on how much FIX is in the plasma, the straw-colored fluid portion of blood.

Normal plasma levels of FIX range from 50% to 150%. Levels below 50%, or half of what is needed to form a clot, determine a person’s symptoms.

  • Mild hemophilia B. 6% up to 49% of FIX in the blood. People with mild hemophilia B typically experience bleeding only after serious injury, trauma or surgery. In many cases, mild hemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild hemophilia often experience menorrhagia, heavy menstrual periods, and can hemorrhage after childbirth.
  • Moderate hemophilia B. 1% up to 5% of FIX in the blood. People with moderate hemophilia B tend to have bleeding episodes after injuries. Bleeds that occur without obvious cause are called spontaneous bleeding episodes.
  • Severe hemophilia B. <1% of FIX in the blood. People with severe hemophilia B experience bleeding following an injury and may have frequent spontaneous bleeding episodes, often into their joints and muscles.

Diagnosis

The best place for patients with hemophilia to be diagnosed and treated is at one of the federally-funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers.

A medical health history is important to help determine if other relatives have been diagnosed with a bleeding disorder or have experienced symptoms. Tests that evaluate clotting time and a patient’s ability to form a clot may be ordered. A clotting factor test, called an assay, will determine the type of hemophilia and its severity

Treatment

The main medication to treat hemophilia B is concentrated FIX product, called clotting factor or simply factor. Recombinant factor products, which are developed in a lab through the use of DNA technology, , preclude the use of human-derived pools of donor-sourced plasma. And while plasma-derived FIX  products are still available, approximately 75% of the hemophilia community takes a recombinant FIX product.

These factor therapies are infused intravenously through a vein in the arm or a port in the chest. The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation encourages the use of recombinant clotting factor products because they are safer. Your doctor or your HTC will help you decide which is right for you.

Patients with severe hemophilia may be on a routine treatment regimen, called prophylaxis, to maintain enough clotting factor in their bloodstream to prevent bleeds. MASAC recommends prophylaxis as optimal therapy for children with severe hemophilia B.

Aminocaproic acid is an antifibrinolytic, preventing the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds. It is taken orally, as a tablet or liquid. MASAC recommends that a dose of clotting factor be taken first to form a clot, then aminocaproic acid, to preserve the clot and keep it from being broken down prematurely.

von Willebrand (VWD) Disease

Von Willebrand disease (VWD) is a genetic disorder caused by missing or defective von Willebrand factor (VWF), a clotting protein. VWF binds factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process. The condition is named after Finnish physician Erik von Willebrand, who first described it in the 1920s.

VWD is the most common bleeding disorder, affecting up to 1% of the US population. It is carried on chromosome 12 and occurs equally in men and women.

Symptoms

People with VWD experience frequent nosebleeds, easy bruising and excessive bleeding during and after invasive procedures, such as tooth extractions and surgery. Women often experience menorrhagia, heavy menstrual periods that last longer than average, and hemorrhaging after childbirth.

There are three main types of VWD based on qualitative or quantitative defects in VWF. A fourth type, acquired VWD, is not hereditary.

  • Type 1 VWD is found in 60%-80% of patients. People with type 1 VWD have a quantitative deficiency of VWF. Levels of VWF in the blood range from 20%-50% of normal. The symptoms are usually mild.
  • Type 2 VWD is found in 15%-30% of patients. People with type 2 VWD have a qualitative deficiency in their VWF. Type 2 is broken down into four subtypes: type 2A, type 2B, type 2M and type 2N, depending on the presence and behavior of multimers, molecular chains of VWF. Symptoms are mild to moderate.
  • Type 3 VWD is found in 5%-10% of patients. People with type 3 VWD have a quantitative deficiency of VWF. Symptoms are typically severe, and include spontaneous bleeding episodes, often into their joints and muscles.
  • Acquired VWD. This type of VWD in adults results after a diagnosis of an autoimmune disease, such as lupus, or from heart disease or some types of cancer. It can also occur after taking certain medications.

Diagnosis

The best place for patients with bleeding disorders to be diagnosed and treated is at one of the federally-funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers.

A medical health history is important to help determine if other relatives have been diagnosed with a bleeding disorder or have experienced symptoms. Tests that evaluate clotting time and a patient’s ability to form a clot may be ordered. A clotting factor test, called an assay, and tests measuring platelet function also may be performed. The VWF antigen test measures the amount of VWF in blood plasma. Patients with VWD typically have <50% of normal VWF in their plasma. After VWD is confirmed, a test to determine the exact type is performed.

It should be noted that diagnostic testing to confirm VWD may have to be repeated because levels of VWF fluctuate. VWF can rise due to stress, exercise, the use of oral contraceptives, pregnancy and hyperthyroidism.

Treatment

Treatment for VWD depends on the diagnosis and severity. The mainstay of treatment is DDAVP (desmopressin acetate), the synthetic version of a natural hormone vasopressin,. It stimulates the release of VWF from cells, which also increases FVIII.DDAVP comes in two forms: injectable and nasal spray. Because DDAVP is an antidiuretic, causing the body to retain water, fluid restrictions are important so patients don’t develop hyponatremia, reduced sodium in the bloodstream.

There are a few clotting factor concentrates that are rich in VWF, and are recommended for patients with VWD. These therapies are given by intravenous infusion. In December 2015, the US Food and Drug Administration (FDA) approved Baxalta’s Vonvendi®, the first recombinant VWF product. Unlike other products, it contains VWF only, not VWF and factor VIII. It is approved to treat on-demand and for control of bleeding in adults 18 and older.

Aminocaproic acid and tranexamic acid are antifibrinolytics agents that prevent the breakdown of blood clots. These drugs are often recommended before dental procedures, to treat nose and mouth bleeds, and for menorrhagia.  Antifibrinolytics are taken orally, as a tablet or liquid. MASAC recommends that a dose of clotting factor be taken first to form a clot, then aminocaproic acid, to preserve the clot and keep it from being prematurely broken down.

Note: Adapted from National Hemophilia Foundation.

Other Factor Deficiencies

In the US, a rare disease or disorder is defined as one that affects fewer than 200,000 people, making hemophilia A and B, and still less prevalent factor deficiencies such as I, II, V, VII, X, XI, XII and XIII, rare disorders. These very rare factor deficiencies, from factor XIII deficiency, the rarest, occurring in an estimated 1 out of 5 million people, to factor XI deficiency, occurring in about 1 out of 100,000, were all discovered and identified in the 20th century. The majority of these conditions were only identified within the last 60-70 years. Here you will find information on how factor deficiencies I, II, V, VII, X, XI, XII and XIII are inherited identified and managed.

Factor 1: Factor 1 deficiency is a collective term for three rare inherited fibrinogen deficiencies.

Factor 2: Learn more out the symptoms, testing and treatment for factor II (FII) deficiency, or prothrombin deficiency.

Factor V: Learn more bout the symptoms, testing and treatment for factor V (FV) deficiency which as several alternate names.

Factor VII: Learn more about the symptoms, testing and treatment for factor VII (FVII) deficiency, or proconvertin deficiency.

Factor X: Learn more about the symptoms, testing and treatment for factor X (FX) deficiency, or Stuart-Prower factor deficiency.

Factor XI: Learn more about the symptoms, testing and treatment for factor XI (FXI) deficiency, which has several alternate names including hemophilia C.

Factor XII: Learn more about factor XII (FXII) deficiency, also called Hageman factor deficiency.

Factor XIII: Learn more about factor XIII (FXIII) deficiency, also called Fibrin Stabilizing Factor Deficiency.

Additional Information about Bleeding Disorders

Internal and External Bleeds: People with bleeding disorders experience external and internal bleeds.

Inhibitors & Other Complications: Having hemophilia and other bleeding disorders can mean coping with various complications that can arise throughout the patient’s lifetime. Some patients have more severe complications, while others have only mild complications. Some of the complications that can occur in patients with hemophilia are discussed here.

Future Therapies: Experimental methods are currently being investigated as possible breakthroughs for curing bleeding disorders.