Grey Platelet Syndrome (GPS)

What are the other Names for this Condition? (Also known as/Synonyms)

• GPS
• Gray Platelet Syndrome (GPS)
• Platelet Alpha-Granule Deficiency

What is Grey Platelet Syndrome? (Definition/Background Information)

• Grey Platelet Syndrome (GPS) is a highly infrequent, inherited bleeding disorder characterized by the presence of unusually large, grey-colored platelets (a type of blood cell), and deficient production of platelet alpha-granules (small particles containing many platelet-related growth factors) in blood
• Bleeding disorders are disorders in which continuous bleeding occurs, following poor blood clotting properties
• GPS is an autosomal recessive condition, meaning that the defective genes are transferred to the child by both parents
• Management of the condition involves anticipating and avoiding any circumstances that can cause a bleeding incident

Who gets Grey Platelet Syndrome? (Age and Sex Distribution)

• Grey Platelet Syndrome affects the newborn child. It is present at birth, but sometimes not discovered until early childhood or even much later, until a bleeding event occurs. However, a blood platelet count test may reveal this disorder much earlier
• The general incidence of this condition is extremely low; only about 60 cases have been described worldwide
• Both sexes are equally affected; no male-female gender inequality is observed
• Among the cases reported, no ethnic or geographical predisposition is seen

What are the Risk Factors for Grey Platelet Syndrome? (Predisposing Factors)

The risk factors for Grey Platelet Syndrome include:

• GPS runs in the families and hence, children born in families with a medical history of the condition are at risk
• Those having consanguineous partners/spouses have the greatest risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Grey Platelet Syndrome? (Etiology)

• Anomalous genetic mutations in gene ‘NBEAL2’ is said to cause Grey Platelet Syndrome. The reason behind the mutations and the exact mechanism of how platelets are affected, is being currently researched upon
• Both parents have to be affected with, or be carriers of the defective genes, for their offspring to be affected with GPS; a feature known as autosomal recessive pattern of inheritance

What are the Signs and Symptoms of Grey Platelet Syndrome?

Generally, mild to moderate bleeding problems are observed with Grey Platelet Syndrome; rarely are they severe. However, the condition may progressively worsen from childhood to adulthood. Key signs and symptoms are:

• Continuous bleeding following injuries, minor cuts & bruises, nosebleeds, and surgeries. In women vaginal bleeding (during a period) can be unusually heavy, and for an extended period
• Enlarged spleen
• Bone marrow fibrosis (which can be observed on a bone marrow biopsy)

How is Grey Platelet Syndrome Diagnosed?

Diagnosis of Grey Platelet Syndrome is made by:

• Physical exam with evaluation of family medical history of the newborn/child/adult
• Blood analysis consisting of platelet and alpha-granule protein examination, platelet count, bleeding time
• Bone marrow biopsy
• Prenatal diagnosis can help when a family history of the condition is known to exist

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Grey Platelet Syndrome?

Complications caused by Grey Platelet Syndrome are:

• Severe bleeding (when platelet count is less than 30,000/microliter) can cause life-threatening situations

How is Grey Platelet Syndrome Treated?

Early detection of Grey Platelet Syndrome bleeding disorder helps create an awareness of the condition, thus anticipating future risks for bleeding. Management measures normally involve forecasting and preventing circumstances that could lead to blood loss, or treating a bleeding situation when it actually occurs. The treatment measures include:

• To prevent bleeding: Women may use oral contraceptives when possible (to reduce vaginal bleeding), maintain dental care and hygiene to avoid bleeding from the gums, avoid medications (like aspirin) that damage platelets, or reduce their function
• Platelet transfusion could be performed prior to any surgical procedure, or if a bleeding situation occurs
• Prescription of desmopressin (a drug used for coagulation disorders) to improve clotting time
• Partial or complete removal of spleen (splenectomy) to help increase platelet count. This procedure is performed rather infrequently

How can Grey Platelet Syndrome be Prevented?

• Currently there are no specific methods or guidelines to prevent Grey Platelet Syndrome genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for  treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Grey Platelet Syndrome? (Outcomes/Resolutions)

• Among the 50-60 cases described worldwide, no fatalities have been reported with Grey Platelet Syndrome. The prognosis is generally good
• The factors that create a very favorable outcome are when GPS is detected early and careful medical follow-up with appropriate and timely treatment is given
• If the platelet count is less than 30,000/microliter, then a severe bleeding situation may result in death

Additional and Relevant Useful Information for Grey Platelet Syndrome:

• A platelet transfusion risk, termed as alloimmunization (which causes the body to gain immunity against some of its own cells), is sometimes higher than the benefits associated with such a transfusion
• Frequent platelet transfusion can cause alloimmunization, which results in the body creating antibodies against the platelets. Such antibodies can destroy the platelets, making platelet transfusion less effective