Related Terms

• Alpha-granule deficiency, desmopressin, GPS, gray platelet syndrome, platelet alpha-granule deficiency, platelet transfusion, thrombocytopenia.

Background

• Gray platelet syndrome (GPS) is a rare inherited condition that affects platelets, whose irregular shape and sticky surface allow them to help form clots to stop blood loss on the inside and outside of the body. In GPS, the platelets do not function properly, which interferes with the process of clotting and may lead to prolonged bleeding time, excessive blood loss, and anemia.

• GPS is caused by decreased or absent alpha-granules, a type of granule, or vesicle, that contains several types of growth factors, such as insulin growth factor, platelet-derived growth factor, platelet factor 4, and other clotting proteins. The platelets in patients with GPS tend to be large and contain few granules, which gives the cells a gray color. Researchers believe that GPS is caused by a genetic mutation or defect, although the specific location of the mutation is currently unknown.

• There is limited information regarding the prevalence of GPS. The condition appears to affect males, females, and individuals of all ethnic and racial groups in equal numbers. The life expectancy of patients with GPS is unknown.

Risk Factors

• Gray platelet syndrome (GPS) is inherited. Therefore, the only known risk factor is a family history of the disorder. GPS is rare, and the exact prevalence of the disorder is not known.

• GPS is believed to be inherited, or passed down among family members, as an autosomal dominant trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit an autosomal dominant trait, an individual needs to inherit only one copy of the defective gene. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.

Causes

• Genetic mutations: Researchers believe that gray platelet syndrome (GPS) is caused by mutations, or defects, in one or more genes. However, these genes have not yet been identified.

• GPS is caused by decreased or absent alpha-granules, which are a type of granule, or vesicle, that contains several types of growth factors, such as insulin growth factor, platelet derived growth factor, platelet factor 4, and other clotting proteins. The platelets in patients with GPS tend to be large and contain few granules, which gives the cells a gray color.

• Autosomal dominant inheritance: GPS is believed to be inherited, or passed down among family members, as an autosomal dominant trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit a dominant trait, an individual needs to inherit only one copy of the defective gene. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.

• Autosomal recessive inheritance: There have been conflicting reports of GPS inherited as an autosomal recessive trait, although this pattern is not commonly accepted for GPS. For an autosomal recessive trait, an individual must inherit two copies of the defective recessive gene, one from each parent, for the disease to occur. Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers, because they can pass on the disorder to their children.

• Random occurrence: It is unknown whether GPS can occur as the result of a spontaneous genetic mutation with no family history of the disease, although there have been reports of this occurrence in some cases.

Signs and Symptoms

• People with gray platelet syndrome (GPS) are prone to thrombocytopenia (abnormal and excessive bleeding episodes). These result from decreased or absent components of platelets, the cells in the blood that help with clotting. People with GPS may experience frequent bruising, nosebleeds, bleeding gums, and gastrointestinal bleeding, and prolonged bleeding during menstruation or childbirth and after dental or other surgery. People with GPS may have an enlarged spleen.

Diagnosis

• Blood test: Blood tests may be used to assess the number and quality of platelets, the cells that help with clotting. Platelets may need to be examined under an electron microscope to detect the distinctive abnormalities of gray platelet syndrome (GPS). Specifically, platelets look pale and can be hard to detect. There is variation in platelet size (called anisocytosis), even though GPS is classified as a large platelet syndrome. GPS is usually suspected based on observation of the characteristic gray appearance of the platelets, which can be seen with the May-Grünwald-Giesma stained blood film.

• Clotting screen procedure: Individuals with GPS may have prolonged bleeding, which can be assessed by measuring clotting time using a clotting screen procedure.

• Western blot analysis: A diagnosis of GPS can be confirmed through Western blot analysis of alpha-granule proteins. Western blot uses gel electrophoresis, which is a technique used for the separation of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or proteins. Using an electric current applied to a gel matrix, proteins are separated by their length or 3-D structure. The proteins are then transferred to a membrane where they are detected using antibodies specific to the target protein, in this case, alpha-granule proteins.

Complications

• Abnormal bleeding: People with gray platelet syndrome (GPS) are prone to abnormal and excessive bleeding episodes, known as thrombocytopenia. These result from decreased or absent components of platelets, the cells in the blood that help with clotting. People with GPS may experience frequent bruising, nosebleeds, bleeding gums, and gastrointestinal bleeding, or prolonged bleeding during menstruation or childbirth, after dental or other surgery, or during childbirth.

• Anemia: Anemia diminishes the capability of affected individuals to perform physical activities. This is a result of a reduced supply of oxygenated red blood cells available to the muscles, causing them to depend instead on anaerobic metabolism. The lack of iron associated with anemia can cause many complications, including hypoxemia, which is inadequate oxygen supply to various organs; brittle or rigid fingernails; cold intolerance; and possible behavioral disturbances in children. Individuals with GPS can develop anemia from the inability of blood to clot, which may lead to excessive bleeding and loss of red blood cells.

Treatment

• General: There is no cure for gray platelet syndrome (GPS). Instead, treatment aims to reduce symptoms and prevent complications. Depending on individual symptoms and complications, individuals with GPS should be regularly seen by a geneticist and a blood disorder specialist.

• Medications: Desmopressin may be provided by injection to improve clotting ability. This drug should not be used in individuals allergic or hypersensitive to desmopressin or in people with platelet-type von Willebrand disease. Side effects of desmopressin include headache, facial flushing, and nausea. The U.S. Food and Drug Administration (FDA) considers desmopressin safe for use by pregnant women, because it has been shown not to cause harm to the fetus. Corticosteroids may be used to increase platelet production and reduce the risk of thrombocytopenic (abnormal and excessive bleeding) episodes. Lithium carbonate may also be used to stimulate the bone marrow production of platelets for this same purpose. Antifibrinolytic agents may also be administered to reduce bleeding and the need for platelet transfusion. Aminocaproic acid (Amicar®) or tranexamic acid (Cyklokapron®) are medications that inhibit the action of certain enzymes that prevent blood clots from forming at a bleeding site. Side effects of both aminocaproic acid and tranexamic acid may include nausea, vomiting, abdominal pain, and diarrhea.

• Medications to avoid: People with gray platelet syndrome (GPS) should not use blood-thinning agents such as aspirin and warfarin, because these agents further inhibit blood clotting. Taking these medications may lead to excessive bleeding in individuals with GPS.

• Patient education: People with GPS should be educated by medical professionals on how to care for themselves. Patient education for individuals with GPS should include the bleeding risks associated with playing contact sports and with surgery, as well as the importance of proper dental care to avoid the need for oral surgery.

• Skin care: Minor cuts that fail to clot should be treated with thrombin-soaked Gelform®, which is a sponge that contains thrombin, a protein that promotes coagulation. Humidifiers may reduce the incidence of nosebleeds.

• Surgical precautions: Individuals with GPS having planned surgery should meet with their hematologist, anesthesiologist, and surgeon beforehand to determine whether drugs such as desmopressin, which may improve blood clotting and decrease bleeding time, should be used.

• Transfusions: Platelet transfusions are used to treat patients with severely low platelet levels who are at high risk of hemorrhage, especially infants. The goal is to maintain healthy platelet levels and prevent bleeding without further complications. Transfusions involve the infusion of platelets from donors and are performed using a small tube connected to a vein in the patient's arm or hand. Platelet transfusions may be used to stop abnormal bleeding during a thrombocytopenic episode but must be performed based on the patient's individual needs. Potential risks of platelet transfusion include infection, anaphylaxis (a multisystem allergic reaction), and hemolytic reactions (allergic reactions to the transfused blood components). Hepatitis viruses (B, C, and others) and the human immunodeficiency virus (HIV) are the most common infective agents that may be transmitted with the transfusion of blood products. The only way to prevent these from being transmitted through a blood transfusion is to thoroughly screen all donated blood for these viruses.

Integrative Therapies

• Note: Currently there is limited scientific evidence on the use of integrative therapies for the treatment or prevention of gray platelet syndrome (GPS). The therapies listed below have been studied for anemia, a potential complication of GPS. These integrative therapies should be used only under the supervision of a qualified healthcare provider and should not replace other proven therapies.

• Strong scientific evidence:

• Iron: Iron is an essential mineral and an important component of proteins involved in oxygen transport and metabolism. Ferrous sulfate (e.g., Feratab®, Fer-Iron®, Slow-FE®) is the standard treatment for treating iron deficiency anemia. Dextran-iron (e.g., INFeD®) is given intravenously to restore adequate iron levels in bone marrow when oral iron therapy has failed.

• Iron is a trace mineral, and hypersensitivity is unlikely. Avoid with known allergy or hypersensitivity to products containing iron. Avoid excessive intake. Avoid iron supplements with blood disorders that require frequent blood transfusions. Use iron supplementation cautiously with a history of kidney disease, intestinal disease, peptic ulcer disease, enteritis, colitis, pancreatitis, hepatitis, or alcoholism; in those who plan to become pregnant; or in those who are over age 55 with a family history of heart disease. Pregnant or breastfeeding women should consult a healthcare professional before beginning iron supplementation.

• Vitamin A: Vitamin A deficiency has been shown to impair the mobilization of iron status and erythropoiesis, and increase susceptibility to infection. Vitamin A supplementation has been shown to raise hemoglobin levels and serum iron concentrations, particularly in children and pregnant women. It has also been shown to enhance the efficacy of iron supplementation in patients with vitamin A deficiency and iron deficiency anemia.

• Vitamin A toxicity can occur if taken at high dosages. Vitamin A appears to be safe in pregnant women if taken at recommended doses. However, vitamin A excess, as well as deficiency, has been associated with birth defects. Vitamin A is excreted in human breast milk. The benefits or dangers to nursing infants are not clearly established. Use cautiously in children and infants. Use cautiously in patients using alcohol, bile acid sequestrants, birth control pills, chemotherapeutic agents (such as busulfan), mineral oil, neomycin, or orlistat. Avoid if allergic or hypersensitive to vitamin A. Avoid with agents toxic to the liver, blood thinners (such as warfarin (Coumadin®)), retinoids, or tetracycline antibiotics. Avoid in patients with liver disease, intestinal infections, fat malabsorption syndromes, severe protein energy malnutrition, or type V hyperlipoproteinemia (a genetic disorder). Avoid high-dose vitamin A and beta-carotene in patients at high risk of lung cancer.

• Vitamin B12: Vitamin B12 deficiency is a cause of megaloblastic anemia, in which red blood cells are larger than normal and the ratio of nucleus size to cell cytoplasm is increased. There are other potential causes of megaloblastic anemia, including folate deficiency or various inborn metabolic disorders. Pernicious anemia is a type of megaloblastic anemia caused by vitamin B12 deficiency, and it should be treated with vitamin B12. Patients with anemia should be evaluated by a physician in order to diagnose and address the underlying cause.

• Vitamin B12 is generally considered safe when taken in amounts that are not higher than the recommended dietary allowance (RDA). There are not enough scientific data available about the safety of larger amounts of vitamin B12 during pregnancy or breastfeeding. Use cautiously in patients with heart problems (including coronary stenting), elevated blood pressure, skin concerns, genitourinary concerns, gastrointestinal concerns, blood disorders, subnormal serum levels of potassium, gout, or elevated uric acid levels. Use cautiously in patients taking the following agents, as they have been associated with reduced absorption or reduced blood levels of vitamin B12: ACE inhibitors, acetylsalicylic acid (aspirin), antibiotics, anticonvulsants, bile acid sequestrants, colchicine, H2 blockers, metformin, neomycin, nicotine, nitrous oxide, oral contraceptives, para-aminosalicylic acid, potassium chloride, proton pump inhibitors (PPIs), and zidovudine (AZT, Combivir®, Retrovir®). Additionally, vitamin C may cause the degradation of vitamin B12 in multivitamin supplements, and chloramphenicol may inhibit the biosynthesis of vitamin B12. Avoid in patients sensitive or allergic to cobalamin, cobalt, or any other vitamin B12 product ingredients.

• Unclear or conflicting scientific evidence:

• Folic acid: The effect of folic acid on iron deficiency anemia is not clear. Well-designed clinical trials of folic acid supplementation are needed in iron-supplemented individuals before a conclusion may be drawn.

• Avoid if allergic or hypersensitive to folate or any folate product ingredients. Use cautiously if receiving coronary stents and with anemia and seizure disorders. It is suggested that pregnant women consume 400 micrograms daily in order to reduce the risk of the fetus developing a defect. Folate is likely safe if breastfeeding.

• Riboflavin: Riboflavin is a water-soluble B vitamin involved in vital metabolic processes in the body, and it is essential for normal cell function, growth, and energy production. Some research suggests that riboflavin may play an adjunct role in the treatment of iron deficiency anemia, and levels of riboflavin may be low in this condition. Correction of riboflavin deficiency in individuals who are both riboflavin deficient and iron deficient appears to improve response to iron therapy.

• Avoid if allergic or hypersensitive to riboflavin. Since the amount of riboflavin a human can absorb is limited, riboflavin is generally considered safe. Riboflavin is generally regarded as safe during pregnancy and breastfeeding. The U.S. recommended dietary allowance (RDA) for riboflavin in pregnant women is higher than that for nonpregnant women, at 1.4 milligrams daily; the RDA is 1.6 milligrams for breastfeeding women.

Prevention

• General: Because gray platelet syndrome (GPS) is inherited, there are no known means of preventing the condition. Because the exact genetic mutation that causes GPS is currently unknown, genetic tests cannot detect the condition in a developing fetus. Precautions can be taken in order to prevent an individual with GPS from bleeding to death.

• Dental care: Individuals with GPS should adhere to a strict schedule of preventive dental care in order to prevent bleeding of the gums.

• Participation in physical activity: Although individuals with bleeding disorders such as GPS can participate in sports, there is a risk of increased bleeding during an injury. Therefore, precautions should be taken to avoid and prepare for such an injury.

• Surgery precautions: Because of their increased risk of bleeding, individuals with GPS who are having planned surgery should meet with their hematologist, anesthesiologist, and surgeon beforehand to determine whether drugs such as desmopressin, which may improve blood clotting ability and decrease bleeding time, should be used.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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