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Inherited Platelet Disorders

Platelets are small cells that circulate in the blood. They are involved in the formation of blood clots and the repair of damaged blood vessels.

When a blood vessel is injured, platelets stick to the damaged area and spread along the surface to stop the bleeding (this process is called adhesion). At the same time, chemical signals are released from small sacks inside the platelets called granules (this process is called secretion). These chemicals attract other platelets to the site of injury and make them clump together to form what is called a platelet plug (this process is called aggregation).

Sometimes the platelet plug is enough to stop the bleeding. However if the wound is large, other proteins called clotting factors are recruited to the site of injury. These clotting factors work together on the surface of the platelets to form and strengthen the blood clot.

What are platelet function disorders?

Platelet function disorders are conditions in which platelets don’t work the way they should, resulting in a tendency to bleed or bruise. Since the platelet plug does not form properly, bleeding can continue for longer than normal.

Since platelets have many roles in blood clotting, platelet function disorders can lead to bleeding disorders of various intensities.

Updated May 2012

What is Bernard-Soulier syndrome?

Bernard-Soulier syndrome is a platelet function disorder caused by an abnormality in the genes for glycoprotein Ib/IX/V. These genes code for a group of linked proteins normally found on the surface of platelets, the glycoprotein Ib/IX/V receptor (also called the von Willebrand factor or VWF receptor). Because this receptor is absent or is not working properly, platelets do not stick to the injured blood vessel wall the way they should and it is difficult for the normal blood clot to form.

Bernard-Soulier syndrome is an autosomal recessive disorder, meaning that both parents must carry an abnormal gene (even though they themselves don’t have the disease) and pass that abnormal gene on to their child. Like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common. Bernard-Soulier syndrome affects both males and females.

Symptoms

Symptoms of Bernard-Soulier syndrome vary from one individual to the next. Signs of the disorder are usually first noticed during childhood.

People with Bernard-Soulier syndrome may experience:

  • Easy bruising
  • Nose bleeds
  • Bleeding from gums
  • Heavy or prolonged menstrual bleeding (menorrhagia) or bleeding after childbirth
  • Abnormal bleeding after surgery, circumcision, or dental work
  • Rarely, vomiting blood or passing blood in stool due to bleeding from the gut (gastrointestinal hemorrhage)

Bernard-Soulier syndrome often causes more problems for women than men because of menstruation and childbirth.

Diagnosis

The diagnosis of platelet function disorders requires a careful medical history and a series of laboratory tests that should be performed by a specialist at a hemophilia treatment centre.

In people with Bernard-Soulier syndrome:

  • The bleeding time (a standardized test of the time it takes for a small cut to stop bleeding) is longer than normal. This test may be difficult to perform in young children
  • The closure time (a test that measures the time it takes for a platelet plug to form in a sample of blood) is longer than normal
  • Platelets appear larger than normal under a microscope
  • There are usually fewer platelets than normal
  • Platelets do not clump together normally in the presence of ristocetin (a substance that normally promotes platelet aggregation)
  • GP Ib/IX/V is not detectable in blood samples (using a test called flow cytometry)
Note: Some tests are not available in all centres.

 

In children, Bernard-Soulier syndrome is sometimes misdiagnosed as immune thrombocytopenic purpura, another type of bleeding problem in which there are also fewer platelets than normal.

Treatment

Most people with platelet function disorders only need treatment during surgical procedures (including dental work) and after injury or accidents. When needed, Bernard-Soulier syndrome may be treated with:

  • Antifibrinolytic drugs
  • Recombinant factor VIIa
  • Desmopressin
  • Fibrin sealants
  • Hormonal contraceptives (to control excessive menstrual bleeding)
  • Iron replacement (if necessary to treat anemia caused by excessive or prolonged bleeding)
  • Platelet transfusions (only if bleeding is severe)

People with inherited platelet function disorders should not take Aspirin®, nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen), and blood thinners, which can make their bleeding symptoms worse.

Updated May 2012

What is Glanzmann thrombasthenia?

Glanzmann thrombasthenia is a platelet function disorder that is caused by an abnormality in the genes for glycoproteins IIb/IIIa. These genes code for a group of linked proteins normally found on the surface of platelets, the glycoprotein IIb/IIIa receptor (also called the fibrinogen receptor). Because this receptor is absent or is not working properly, platelets do not stick to each other at the site of injury and it is difficult for the normal blood clot to form.

Glanzmann thrombasthenia is an autosomal recessive disorder, meaning that both parents must carry an abnormal gene (even though they themselves don’t have the disease) and pass that abnormal gene on to their child. Like all autosomal recessive disorders, it is found more frequently in areas of the world where marriage between close relatives is common. Glanzmann thrombasthenia affects both males and females.

Symptoms

Symptoms of Glanzmann thrombasthenia vary quite a bit from one individual to the next, from very mild to potentially life-threatening bleeding. Signs of the disorder are usually first noticed during childhood.

People with Glanzmann thrombasthenia may experience:

  • Easy bruising
  • Nose bleeds
  • Bleeding from gums
  • Heavy or prolonged menstrual bleeding (menorrhagia) or bleeding after childbirth
  • Abnormal bleeding after surgery, circumcision, or dental work
  • Rarely, vomiting blood or passing blood in urine or stool due to bleeding in the gut (gastrointestinal hemorrhage) or genito-urinary tract (kidneys, ureters, bladder, and urethra)

Glanzmann thrombasthenia often causes more problems for women than men because of menstruation and childbirth.

Diagnosis

The diagnosis of platelet function disorders requires a careful medical history and a series of tests that should be performed by a specialist at a hemophilia treatment centre.

In people with Glanzmann thrombasthenia:

  • The bleeding time (a standardized test of the time it takes for a small cut to stop bleeding) is longer than normal. This test may be difficult to perform in young children
  • The closure time (a test that measures the time it takes for a platelet plug to form in a sample of blood) is longer than normal
  • Platelets do not clump together the way they should with several different chemicals in a laboratory test (platelet aggregation)
  • GP IIb/IIIa is not detectable in blood samples (using a test called flow cytometry)
Note: Some of these tests may not be available in all centres.

 

Treatment

Most people with platelet function disorders only need treatment during surgical procedures (including dental work) and after injury or accidents. When needed, Glanzmann thrombasthenia may be treated with:

  • Antifibrinolytic drugs
  • Recombinant factor VIIa
  • Fibrin sealants
  • Hormonal contraceptives (to control excessive menstrual bleeding)
  • Iron replacement (if necessary to treat anemia caused by excessive or prolonged bleeding)
  • Platelet transfusions (only if bleeding is severe)

People with inherited platelet function disorders should not take Aspirin®, nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen), and blood thinners, which can make their bleeding symptoms worse.

Updated May 2012

What are storage pool deficiencies?

Storage pool deficiencies are a group of disorders caused by problems with platelet granules. Granules are little sacks inside the platelet in which proteins and other chemicals important to its function are stored. There are two types of granules: alpha granules and dense granules.

Some storage pool deficiencies are caused by a lack of granules, but the most common ones are caused by a failure of the platelets to empty the contents of the granules into the bloodstream (this is called the secretory or release mechanism).

  • Release defects are a diverse group of disorders caused by a problem with the secretory mechanism. Even though the granules are present within the platelets, their contents are not emptied into the bloodstream properly.
  • Delta storage pool deficiency is a platelet function disorder caused by a lack of dense granules and the chemicals normally stored inside them. Without these chemicals, platelets are not activated properly and the injured blood vessel does not constrict to help stop bleeding. This type of bleeding problem can be a feature of other inherited conditions (such as Hermansky-Pudlak syndrome and Chediak-Higashi syndrome).
  • Grey platelet syndrome is a very rare platelet function disorder caused by a lack of alpha granules and the chemicals normally stored inside them. Without these proteins, platelets can not stick to the blood vessel wall, clump together the way they should, or repair the injured blood vessel.

Symptoms

Symptoms of storage pool deficiencies vary from one individual to the next, but they are usually mild to moderate.

People with storage pool deficiencies may experience:

  • Easy bruising
  • Nose bleeds
  • Bleeding from gums
  • Heavy or prolonged menstrual bleeding (menorrhagia) or bleeding after childbirth
  • Abnormal bleeding after surgery, circumcision, or dental work

Diagnosis

The diagnosis of storage pool deficiencies requires a careful medical history and a series of tests that should be performed by a specialist at a hemophilia treatment centre.

In people with storage pool deficiencies:

  • The bleeding time (a standardized test of the time it takes for a small cut to stop bleeding) is often longer than normal. This test may be difficult to perform in young children
  • Platelets do not clump together the way they should in special laboratory tests (platelet aggregation)
  • Granules may not be visible when platelets are looked at with an electron microscope

Treatment

Most people with storage pool deficiencies only need treatment during surgical procedures (including dental work) and after injury or trauma. When needed, storage pool deficiencies may be treated with:

  • Antifibrinolytic drugs
  • Desmopressin (may not be useful in alpha granule deficiency)
  • Platelet transfusions

People with inherited platelet function disorders should not take Aspirin®, nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen), and blood thinners, which can make their bleeding symptoms worse.

Updated May 2012