Inherited Platelet Disorders
There are many different kinds of platelet function disorders. They can be divided into two categories:
- hereditary disorders (meaning that they run in the family)
- acquired disorders (meaning they are caused by other diseases or the use of medications).
Disorders of platelet adhesion
This rare disorder is called Bernard-Soulier Syndrome and is named after the two French haemotologists who discovered it. It is caused by a deficiency of Glycoprotein Ib/IX, the receptor for von Willebrand factor. Platelets are typically abnormally large, resulting in platelets failing to adhere to one another and assemble at the site of injury.
Usually, diagnosis happens at a young age, particularly when a family history is present. Children may present with bruises, and nose/mouth/gum bleeds for example after a visit to the dentist. There may also be incidence of gastrointestinal bleeding. In women, a symptom is heavy menstrual bleeding. Men and women are affected equally, but it is rare, with an estimated 50 patients in the UL.
Two copies of the mutant gene are inherited one each from the mother and father. It is thus more common in families where relationships between blood relatives exist. In general carriers who only have one mutated gene do not experience any clinical problems, although there are exceptions
Blood tests confirm a longer than normal measure of time for bleeding to cease e.g. from a small wound, as well as a lower than usual platelet count. Under a microscope, platelets appear larger than normal, and do not clump together as expected. Treatment should be recommended by a haematologist with experience in bleeding disorders. Treatment is in line with other platelet disorders. This includes but isn’t limited to avoidance of medications that inhibit platelet function further such as aspirin and treatment by platelet transfusion.
Disorders of platelet aggregation
Glanzmann Thrombasthenia is a life-threatening deficiency of a protein on the surface of the platelet, called Glycoprotein IIb/IIIa. As a result, platelets fail to stick together at the site of injury meaning blood cannot clot. As with Bernard-Soulier Syndrome, children experience easy bruising, nasal, mouth and gum bleeds and women are liable to heavy or prolonged bleeding (menorrhaegia) during childbirth.
Women may experience heavy or prolonged menstrual bleeding (menorrhagia) and bleeding at the time of childbirth. With disorders of platelet aggregation, patients bleed longer than is usual and platelets do not clump at all.
Disorders of platelet secretion
There are at least three disorders of platelet secretion dysfunction:
Alpha Granule Deficiency
Alpha Granule Deficiency, also known as Gray Platelet Syndrome, is characterised by a scarcity of important proteins within the platelet’s alpha granule. As a consequence, functions of platelet adhesion, aggregation and blood vessel repair are
Bleeding time is usually long and the platelet count may be low. A test of platelet aggregation shows some abnormalities. Seen through a microscope, platelets show an absence of granules.
In Dense Granule Deficiency
called Delta Storage Pool Deficiency, there is a lack of storage granules for certain substances needed for normal platelet activation. Their absence slows down platelet activation and blood vessel constriction. (See Figure 1, stages 2 and 3.)
Bleeding time is sometimes longer than normal. A platelet aggregation test shows an abnormal pattern. Examination of the platelets using an electron microscope shows an absence of dense granules.
Some people with this disorder also have abnormalities in hair colour, difficulties with vision and are more prone to infection.
Abnormalities of the granule secretory mechanism
These occur when the normal granules fail to release their contents when platelets are activated. People with this disorder have platelet dysfunction like that of individuals who have been given drugs such as aspirin to stop their platelets from clumping together.
Disorders of platelet procoagulant activity
This very rare disorder is called Scott Syndrome. Platelets fail to promote activation of the blood clotting proteins which are necessary in the formation of the fibrin clot. (See Figure 1, stage 4.)
Bleeding time and platelet aggregation are normal but there are abnormalities of the platelet surface membrane. Specific tests are required to determine platelet procoagulant activity if this disorder is suspected.
Combined abnormalities of number and function
Some hereditary disorders of platelet production show low platelet counts and platelets of abnormal size. Many of these conditions are associated with other medical problems such as:
- May-Hegglin Anomaly
- Alport Syndrome
- Wiskott-Aldrich Syndrome
The Haemophilia Society can advise in relation to inherited bleeding disorders Hereditary platelet function disorders can be divided into five groups depending on the type of abnormality: