Facts

Overview | Hemophilia | Von Willebrand Disease | Rare Factor Deficiencies | Rare Platelet Disorders

Overview

Bleeding Disorders Vary Greatly in Severity and Frequency

“Bleeding disorder” is a general term for a wide range of medical problems that lead to poor blood clotting and prolonged bleeding. Health care providers call these conditions by many different terms, including coagulopathy, abnormal bleeding, and clotting disorders.

Each bleeding disorder has its own range of severity, which is generally categorized as mild, moderate, or severe. Approximately 20,000 individuals in the United States have hemophilia and up to 1% - 2% of the population has von Willebrand Disease (VWD), the most common type of bleeding disorder. Each of these disorders causes bleeding and each can be treated.

Hemophilia: there are several different types of hemophilia. The two most common are:

  • Hemophilia A (called classic hemophilia)
  • Hemophilia B (called Christmas disease)

von Willebrand Disease: researchers have identified many variations of this bleeding disorder, but most fall into the following classifications:

Type 1, 2, or 3
Subtype 2B, 2M or 2N

  • Rare Factor Deficiencies: there are several rare, inherited bleeding disorders in which one or more clotting factors are not in the blood, are only in small amounts, or don’t work properly:
  • Factor I (1) deficiency
  • Factor II (2) deficiency
  • Factor V (5) deficiency
  • Combined factor V (5) and VIII (8) deficiency
  • Factor VII (7) deficiency
  • Factor X (10) deficiency
  • Factor XI (11) deficiency
  • Factor XIII (13) deficiency

Rare Platelet Disorders: there are several rare bleeding disorders in which platelets lack a protein needed for blood to clot. These disorders are inherited in autosomal recessive fashion:

  • Bernard-Soulier syndrome
  • Glanzmann’s thrombasthenia
  • Platelet storage pool disease

BLEEDING DISORDERS FACTS adapted from the National Hemophilia Foundation©2011 All Rights Reserved

Bleeding Disorders FACTS

Types of Bleeding Disorders: Description, Diagnosis, and Treatment

Overview | Hemophilia | Von Willebrand Disease | Rare Factor Deficiencies | Rare Platelet Disorders

HEMOPHILIA

Description
Hemophilia is an inherited (genetically passed to the child through the parent’s DNA) bleeding disorder in which the blood does not clot properly. The overwhelming majority of people with hemophilia are males.

Blood contains many proteins (called clotting factors) that help stop bleeding. These clotting factors are numbered from 1 through 13, using roman numerals (such as I or X). People with hemophilia have either a low level of these clotting factors in their blood or none at all. The lower the level of clotting factor, the more serious the hemophilia. The result: problems, such as bleeding without an obvious cause and prolonged bleeding after an injury or surgery, are more likely.

There are three different types of hemophilia:

  • Hemophilia A (called classic hemophilia): this type is caused by a lack or decrease of clotting factor VIII (8)
  • Hemophilia B (called Christmas disease): this type is caused by a lack or decrease of clotting factor IX (9)
  • Hemophilia C (called Factor XI [11] deficiency)

Diagnosis
Many people who have or have had family members with hemophilia will ask that their male infants be tested soon after birth. It is important to remember, however, that about one-third of people who are diagnosed with hemophilia have no family members with the disorder. In these cases, hemophilia is caused by a spontaneous genetic mutation. A healthcare provider might check for hemophilia if a newborn shows certain signs; for example, a baby might bleed more than normal after being circumcised.

Screening tests and clotting factor tests, both of which are blood tests, are used to diagnose hemophilia. Screening tests show if the blood is clotting properly. Clotting factor tests (called factor assays) are used to confirm a diagnosis of a bleeding disorder. Factor assays are used to pinpoint the type of hemophilia and its severity. With this information, a health care provider can create the best treatment plan.

The table below shows the various levels of severity in hemophilia:

Severity Level of Factor VIII (8) or IX (9) in the blood
Normal (person who does not have hemophilia) 50%-100%
Mild hemophilia Greater than 5% but less than 50%
Moderate hemophilia 1%-5%
Severe hemophilia Less than 1%


Treatments
"The information contained in this Web site is provided for your general information only. It is not intended as a substitute for visiting with your physician, nurse, or social worker. GLHF  does not give medical advice or engage in the practice of medicine. GLHF  under no circumstances recommends particular treatments for specific individuals and in all cases recommends that you consult your physician or local treatment center before pursuing any course of treatment."

Hemophilia is a complex disorder and, therefore, requires a multifaceted approach. The goal of treatment is to prevent bleeds and the damage associated with bleeding. Quality medical care from health care providers with expertise in this bleeding disorder can help prevent many serious problems. Often the best choice for care is a comprehensive Hemophilia Treatment Center (HTC).

A Hemophilia Treatment Center provides care to address all issues related to the bleeding disorder, as well as offers patient and caregiver education.

The HTC team consists of physicians (hematologists), nurses, social workers, physical therapists, and other health care professionals who specialize in the care of people with bleeding disorders.

The best way to treat hemophilia is to replace the missing clotting factor.

Replacing the missing blood clotting factor is done by injecting commercially prepared clotting factor concentrates into a person’s vein. The two main types of clotting factor concentrates available are:

  • Plasma-derived factor concentrates: plasma is the liquid part of blood. It is pale yellow or straw colored and contains proteins such as antibodies, albumin, and clotting factors. Several factor concentrates made from human plasma proteins are available. The clotting proteins are separated from other parts of the plasma, purified, and made into a freeze-dried product. This product is tested and treated to kill any potential viruses before it is packaged for use.
  • Recombinant factor concentrates: before 1992, all factor replacement products were made from human plasma. In that year, the US Food and Drug Administration approved recombinant factor VIII (8) concentrate, which differs from plasma-derived products in two ways: they are either completely free of human plasma or use tiny amounts of pasteurized human serum albumin for cell culture or as a stabilizer. Pasteurized human serum albumin has a 50-year safety record. Recombinant factors VIII (8) and IX (9) are available and do not contain any plasma or albumin and, therefore, cannot transmit any viruses that are known to be transmitted in blood.

Creating Recombinant Factor Concentrates
Here is a quick description of the process used to create recombinant factor concentrates:

  1. The human factor VIII (8) (or IX [9]) gene is isolated through genetic engineering. The gene contains the code that instructs the cell on how to make human factor VIII (8) or IX (9)
  2. The gene is inserted into nonhuman cells, such as baby hamster kidney cells or Chinese hamster ovary cells
  3. These cells are grown in a cell culture, where they produce factor VIII (8) or IX (9)
  4. The factor VIII (8) or IX (9) is separated from the cell culture and purified
  5. A sugar is then added to some products to stabilize the final factor VIII (8) or IX (9) product

The products can be used as needed when a person is bleeding or they can be used routinely to help prevent bleeds. Today, people with hemophilia and their families can learn how to give clotting factors at home (called home therapy). Giving factor at home means that bleeds can be treated quicker, resulting in less serious bleeding, as well as fewer long-term problems.

Other treatment products include:

  • Desmopressin acetate (DDAVP): a synthetic form of the naturally occurring hormone that helps to release factor VIII (8) from where it is stored in the body’s tissues. For people with mild, and some cases of moderate, hemophilia, it can help increase their own factor VIII (8) levels enough so that they do not have to use a clotting factor. This medicine can be given through a vein or by nasal spray.
  • Epsilon amino caproic acid and tranexamic acid: chemicals that prevent clots from breaking down, resulting in a firmer clot. This medicine is often used to prevent bleeding in the mouth or after a tooth has been removed because it blocks an enzyme in the saliva that causes clots to come apart. Amino caproic acid can be given in a vein or taken by mouth (as a pill or a liquid). Tranexamic acid can be given as an injection or by mouth (as a pill).

BLEEDING DISORDERS FACTS adapted from the National Hemophilia Foundation©2011 All Rights Reserved

 

Bleeding Disorders FACTS

Types of Bleeding Disorders: Description, Diagnosis, and Treatment

Overview | Hemophilia | Von Willebrand Disease | Rare Factor Deficiencies | Rare Platelet Disorders

VON WILLEBRAND DISEASE

Description
von Willebrand disease (VWD) is a disorder that is caused by a problem with one of the proteins in the blood (von Willebrand factor or vWF). People with VWD either don’t have enough vWF or what they have doesn’t work properly.

vWF plays two important roles in blood clotting. It makes platelets stick to the wall of an injured blood vessel and to each other. Without it, a platelet plug cannot be made. vWF is also a called acarrier protein because it carries one of the clotting factors, factor VIII (8), with it. This means that it helps make sure there is enough factor VIII (8) in the blood and that it gets to where it’s needed. Without vWF, factor VIII (8) will be broken down in the bloodstream and there may not be enough of it to stop bleeding.

There are several different classifications of VWD.

Classifications of von Willebrand Disease
Type 1 Most common and mildest form

A person with Type 1 VWD has lower-than-normal levels of vWF and may also have low levels of factor VIII, which is another type of blood-clotting protein
 

Type 2 Body makes normal amounts of vWF but it does not work the way it should

Type 2 VWD is further broken down into four Subtypes?2A, 2B, 2M, and 2N? depending on the specific problem with the person’s vWF.

Each type is treated differently
Subtype 2A vWF levels are reduced, as is the ability of platelets to clump together
Subtype 2B Although the factor itself is defective, the ability of platelets to clump together is actually increased
Subtype 2M vWF levels are decreased and the interaction of vWF with platelets or connecting tissue is reduced
Subtype 2N Binding of vWF to factor VIII (8) is markedly decreased
Type 3 Most severe form of VWD; a person has very little or no vWF and low levels of factor VIII (8)

 

Diagnosis
Some people may have VWD for years and never know it because they don’t have symptoms or their symptoms are so mild they’re easily overlooked.

The signs and symptoms of VWD are similar in both men and women. Bleeding in persons with VWD usually involves the mucous membranes of the body. Many people may not be diagnosed because their symptoms are subtle, ignored, or believed to be caused by something else. Some of these symptoms include frequent nosebleed, easy bruising, heavy menstrual bleeding (called menorrhagia) and prolonged bleeding after surgery, childbirth or dental work.

A combination of blood tests is needed to diagnose VWD. In fact, these tests may need to be repeated several times before a definitive diagnosis can be made, because the amount of clotting factor in the blood can vary over time (for example, during pregnancy or if the person has an infection), which can affect the test results.

Treatment
"The information contained in this Web site is provided for your general information only. It is not intended as a substitute for visiting with your physician, nurse, or social worker. NHF does not give medical advice or engage in the practice of medicine. NHF under no circumstances recommends particular treatments for specific individuals and in all cases recommends that you consult your physician or local treatment center before pursuing any course of treatment."

Treatments may be given by injection, nasal spray, or pills. The treatment for VWD depends on the type and severity of the bleeding disorder. For minor bleeds, treatment might not be needed.

The most commonly used treatments are:

  • Desmopressin acetate (DDAVP) injection: this medicine is injected into a vein or just under the skin to treat milder forms of VWD (mainly Type 1). DDAVP is the synthetic form of a naturally occurring hormone. It works by making the body release more vWF into the blood from storage sites along the blood vessel walls. This helps the body form a stable, firm clot and increase the level of factor VIII (8) in the blood.
  • Desmopressin acetate (DDAVP) nasal spray: this spray is the nasal form of the injection. This high-dose nasal spray is used to treat milder forms of VWD. It works by boosting the levels of vWF and factor VIII (8) in the blood.
  • Factor replacement therapy: the plasma-derived clotting factor products used to treat VWD are rich in vWF and factor VIII (8). They are used to treat more severe forms of VWD or milder forms of VWD in people who do not respond well to desmopressin acetate given either by nasal spray or injection. These clotting factor products are injected into a vein in the arm to replace the missing factor in the blood.
  • Antifibrinolytic drugs: these drugs help slow or prevent the breakdown of blood clots. They are either injected or taken orally.
  • Birth control pills (called oral contraceptives): the hormones in birth control pills can increase the levels of vWF and factor VIII (8) in the blood and reduce menstrual blood loss. A healthcare provider can prescribe these pills for heavy menstrual bleeding (called menorrhagia).

BLEEDING DISORDERS FACTS adapted from the National Hemophilia Foundation©2011 All Rights Reserved

 

Bleeding Disorders FACTS

Types of Bleeding Disorders: Description, Diagnosis, and Treatment

Overview | Hemophilia | Von Willebrand Disease | Rare Factor Deficiencies | Rare Platelet Disorders

RARE FACTOR DEFICIENCIES

Description
A number of rare bleeding disorders exist. People with these rare disorders will find specialized treatment at a Hemophilia Treatment Center (HTC) under the care of a specialty hematologist.
Because these deficiencies are so rare, there may be no standard treatment in many cases. So, it’s important to work closely with an experienced hematologist to find the most appropriate treatment.

Clotting factors are proteins in the blood that control bleeding. If any of the clotting factors is missing or not working properly, the normal steps leading to coagulation are blocked. When this happens, the blood clot does not form and the bleeding continues for longer than it should. A deficiency of any one of these clotting factors can cause a rare bleeding disorder.


BLEEDING DISORDERS FACTS adapted from the National Hemophilia Foundation©2011 All Rights Reserved

 

Bleeding Disorders FACTS

Types of Bleeding Disorders: Description, Diagnosis, and Treatment

Overview | Hemophilia | Von Willebrand Disease | Rare Factor Deficiencies | Rare Platelet Disorders

RARE PLATELET DISORDERS

Description
A number of rare platelet bleeding disorders exist. People with these rare disorders will find specialized treatment at a Hemophilia Treatment Center (HTC) under the care of a hematologist. Rare platelet disorders may be inherited or acquired after birth. These disorders can last a short time or be a chronic condition. Platelet disorders are usually milder than the other types of bleeding disorders.

 

There’s much we don’t know about platelet disorders. In some cases, patients may only know they have an “unspecified” platelet disorder.

Platelets are tiny, irregularly shaped blood cell pieces (called fragments) that play an important role in clotting blood. When an injury occurs and a blood clot is needed, the platelets become sticky and help plug the site of the injury. They attract other proteins needed in the clotting process and they help form a stable clot. There are several ways or reasons that platelets may not work properly.

The specific problem may result in rare platelet disorders, such as:

  • Bernard-Soulier Syndrome (BSS): a very rare platelet disorder that causes a deficiency of glycoprotein lb, the receptor for von Willebrand factor, which is important in clot formation. A person with BSS can bleed for a very long time before a clot forms. In fact, it may take more than 20 minutes for the bleeding to stop from even a small cut.
  • Laboratory tests are needed to diagnose BSS. Some people with BSS have only slightly lower-than- normal platelet counts. Interestingly, under a microscope, the platelets of people with BSS are much larger than normal.
  • Glanzmann’s Thrombasthenia (GT): an extremely rare bleeding disorder in which the platelets lack glycoprotein IIb/IIIa, the binding sites for von Willebrand factor, on the surface. In people with GT, platelets do not adhere or stick to each other as they should. Bleeding continues significantly longer than normal.
  • Laboratory tests are necessary to diagnose GT. In people with GT, the platelet count is normal. Under a microscope, their platelets are normal in size and shape. Blood tests are available to check for deficiency of glycoprotein IIb/IIIa in the platelets.
  • Platelet Storage Pool Disease (SPD): a name given to several rare disorders in which the platelet granules are affected. During the process of making a platelet plug, the platelets change shape. Chemicals inside the granules are pushed out (called secretion) into the bloodstream, signaling other platelets to the plug. In SPD, a certain type of granule in the platelets may be missing or be abnormal. The result: the body takes longer to form a clot.
  • SPD usually causes mild to moderate bleeding. While bleeding lasts longer than normal, usually the bleeding does stop. People with SPD rarely require treatment except when they are having surgery or have a serious injury. Blood tests are needed to diagnose SPD

BLEEDING DISORDERS FACTS adapted from the National Hemophilia Foundation©2011 All Rights Reserved