The symptoms of Glanzmann thrombasthenia usually begin at birth or shortly thereafter and include the tendency to bruise and bleed easily and sometimes profusely, especially after surgical procedures. Other symptoms may include susceptibility to easy bruising, nosebleeds (epistaxis), bleeding from the gums (gingival), intermittent gastrointestinal bleeding, and/or variably large red or purple colored spots on the skin that are caused by bleeding in the skin (purpura). Women with GT often also have unusually heavy menstrual bleeding, irregular uterine bleeding, and excess bleeding in childbirth. Rarely, internal bleeding and blood in the urine (hematuria) can occur. The severity of the symptoms varies greatly. Some affected individuals have mild bruising and others have severe hemorrhages that can be life threatening.
Glanzmann thrombasthenia is inherited as an autosomal recessive genetic trait. An abnormality in one or the other genes for the platelet aIIbb3 (GPIIb/IIIa) integrin family receptor prevents platelets from forming a plug when bleeding occurs. The genes for the receptor proteins aIIb (glycoprotein IIb; GPIIb) and ß3 (glycoprotein IIIa; GPIIIa) are located on the long arm of chromosome 17 (17q21.32). Many different abnormalities in these genes have been identified.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. This is true for carriers of Glanzmann thrombasthenia. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive the normal genes from both parents and therefore be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Glanzmann thrombasthenia is a rare disorder that affects males and females in equal numbers. The symptoms of this disease are usually apparent at birth (neonates) or during infancy. Approximately 300 cases have been reported. This condition occurs with greater frequency in populations in which intermarriage within a group (consanguinity) is more prevalent such as in some regions of the Middle East, India, and France.
Most individuals affected with Glanzmann thrombasthenia have a normal number of platelets but have a prolonged bleeding time, which means it takes longer than usual for a standardized cut to stop bleeding. Platelet aggregation studies are abnormal and show that platelets are not able to clump together when stimulated as they should to form platelet aggregates. Glanzmann thrombasthenia is definitively diagnosed by tests that determine if there is a deficiency of the aIIbb3 (GPIIb/GPIIIa) receptor. These tests usually involve monoclonal antibodies and flow cytometry. Genetic tests can identify the DNA mutations responsible for the disorder.
Carrier and prenatal testing by DNA analysis is possible if the specific gene abnormality has been identified in an affected family member.
Some individuals with GT may require blood platelet transfusions. Since transfusions may continue to be necessary throughout life, affected individuals may benefit from transfusions from HLA matched donors. Activated factor VII (FVIIa) is an experimental therapy that has shown benefit in patients with GT. It is a recombinant protein and so does not have the infectious and other risks associated with blood platelets. It has a risk of increased blood clots, but that appears to be rare in GT patients.
Treatment is usually given prior to most surgical procedures or should be available if needed. Platelet transfusions are sometimes necessary prior to delivery.
Nosebleeds can usually be treated with nasal packing or application of foam soaked in thrombin. Regular dental care is important to prevent bleeding from the gums.
Hormonal therapy can be used to suppress menstrual periods.
Other treatment of GT is symptomatic and supportive.
Genetic counseling may be of benefit for people with GT and their families.
Bone marrow transplantation has successfully cured a few patients with severe disease.
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