Introduction:
Platelets are an important part of hemostasis. The damaged subendothelium releases adhesion proteins and fibrinogen that combine with platelets that are aggregated at the injury site to form a platelet plug. Platelets provide a surface and phospholipid source for the binding of clotting cofactors. Subsequent activation results in adhesion to activated platelets and thrombus formation. Impairments in platelet function, whether acquired or hereditary, lead to bleeding.
Acquired platelet disorders are likely to occur in the clinical setting and are often attributed to drug initiation or underlying disease. In contrast, hereditary platelet disorders are rare and poorly studied. Glanzmann thrombasthenia (GT) is one of today's most well-known diseases associated with abnormal hemostasis. This helped pave the way for important research in hematology.
Eduard Glanzmann was a Swiss pediatrician who first discovered thrombotic conditions in 1918. Formerly known as "hereditary hemorrhagic thrombosis," Glanzmann recognized the disorder as not due to abnormal numbers of platelets but due to defects in thrombus retraction, paving the way for future research.
What Are the Other Names of Glanzmann Thrombasthenia?
Glanzmann thrombasthenia is known by various other names as well. They are as follows:
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Deficiency of GP 2B 3A complex.
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Dicyclo thrombopathia 2B 3A.
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Glanzmann thrombasthenia type A.
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Platelet fibrinogen receptor.
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Platelet glycoprotein 2B 3A deficiency.
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Thrombasthenia of Glanzmann and Naegeli.
What Is Glazmann Thrombasthenia?
Glanzmann thrombasthenia (GT) is an unusual hereditary bleeding disorder denoted by the dysfunction of specialized blood cells called platelets that are essential for proper blood clotting. Symptoms of this condition usually include breakthrough bleeding, which can be serious too. Prolonged untreated or unsuccessful bleeding associated with Glanzmann thrombosis can be life-threatening.
What Causes Glazmann Thrombasthenia?
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Glanzmann thrombasthenia is an autosomal recessive genetic disorder. Abnormalities in the IIb (glycoprotein IIb; GPIIb) gene or the β3 (glycoprotein IIIa; GPIIa) gene result in abnormal receptors for the platelet IIbβ3 (GPIIb/IIIa) integrin family, preventing platelets from forming thrombi during bleeding.
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Various types of gene abnormalities have been seen with this disorder. Recent scientific evidence claims that around 0.5 % of healthy individuals in the general population are likely to carry genes with aberrant variants in aIIb or β3.
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Genetic diseases are characterized by the gene combination for specific traits on the chromosomes of the father and the mother. Recessive genetic disorders occur when a person inherits an abnormal gene variant from each parent. A person with one normal gene and one abnormal gene variant is a carrier but usually has no symptoms. This applies, for example, to carriers of Glanzmann thrombosis as well.
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The risk of two carrier parents transmitting the defective gene, resulting in an affected child, is 25 % in each pregnancy. In all pregnancies, there is a 50 % chance of having a child who is a carrier like both parents. A child has a 25 % chance of inheriting normal genes from both parents and being genetically normal for that particular trait. Men and women are at the same risk for this disorder.
What Are the Signs and Symptoms Associated With Glanzmann Thrombasthenia?
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The symptoms of Glanzmann thrombasthenia usually begin at birth or shortly thereafter, with easy bruising, bleeding, and sometimes profuse bleeding, especially after surgery.
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Other symptoms include easy bruising, nosebleeds (epistaxis), bleeding gums, intermittent gastrointestinal bleeding, and red or purple spots of various sizes caused by skin bleeding (purpura).
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Women with GT also often have heavy menstrual bleeding, irregular uterine bleeding, and heavy bleeding during childbirth.
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In rare cases, internal bleeding or hematuria (presence of blood in urine) may occur. The severity of symptoms varies greatly. Some people bruise easily, while others have severe bleeding that can be life-threatening.
How Is Glanzmann Thrombasthenia Diagnosed?
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Most people with Glanzmann thrombosis have average platelet counts. Still, they have a longer bleeding time, so a standardized cut will take longer than usual to stop bleeding. Furthermore, platelet aggregation studies are aberrant, indicating that platelets cannot aggregate when stimulated, as they should normally form platelet aggregates.
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Glanzmann thrombasthenia is definitively diagnosed by testing to determine whether a person has a receptor deficiency of αIIbβ3 (GPIIb/GPIIIa). These tests typically include monoclonal antibodies and flow cytometry. In addition, genetic testing can identify DNA mutations that cause the condition.
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If a certain genetic abnormality has been identified in an affected family member, then the carrier and prenatal testing by DNA analysis is feasible. Otherwise, prenatal testing can be done based on the analysis of fetal platelet aIIbβ3.
How Is Glanzmann Thrombosthenia Treated?
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Some people with GT need platelet transfusions. Because blood transfusions can be lifelong, affected individuals may benefit from transfusions from HLA-matched donors.
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Some patients may develop antibodies to the transfused platelets, reducing the benefit of subsequent platelet transfusions.
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In 2014, NovoSeven RT, a recombinant factor VIIa product, was approved for the treatment of Glanzmann thrombasthenia. This drug is indicated for the management of bleeding episodes and perioperative management when platelet transfusions are ineffective. Novo Nordisk manufactures NovoSeven RT.
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The treatment is usually given before most surgical procedures or should be available when needed. Platelet transfusions are usually required before birth.
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Nosebleeds are generally treated by nasal packing or thrombin-soaked foam. Regular and proper dental care is imperative for the prevention of gum bleeding.
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Hormone therapy can be used to suppress increased menstrual bleeding.
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Other treatments for GT include symptomatic and supportive care, including antifibrinolytics.
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Genetic counseling is recommended for GT patients and their families.
Conclusion:
Glanzmann thrombasthenia (GT) is a rare congenital bleeding disorder that occurs at birth. It is characterized by the dysfunction of specialized blood cells called platelets that are essential for proper blood clotting. Signs and symptoms vary significantly from person to person. However, symptoms usually include severe abnormal bleeding. The condition is inherited in an autosomal recessive manner and is caused by genetic alterations in the ITGA2B or ITGB3 genes. Its early diagnosis, proper management of symptoms, and adequate treatment can help better handle the condition.
