English Version
C.R. Degrandi Oliveira

Glanzmann’s thrombasthenia

Glanzmann’s thrombasthenia

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Keywords Glanzmann’s thrombasthenia; ICD 10: D69.1; OMIM: 273800, 619267; Synonyms: Glanzmann syndrome; Glanzmann-Nägeli syndrome; Glycoprotein IIb (GPIIb/III) complex deficiency; Haemorrhagic thrombasthenia; Hereditary thrombasthenia; Hereditary thrombocytopenic purpura; Platelet fibrinogen receptor deficiency; Platelet glycoprotein IIb/IIIa deficiency; Thrombasthenia; Thrombocytasthenia. 
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Glanzmann's thrombasthenia (GT) is an autosomal recessive platelet function disorder caused by mutations in the ITGA2B and ITGB3 genes (chromosome 17) encoding the αIIbβ3 integrin, leading to abnormality of the platelet membrane glycoprotein complex IIb/IIIa. Genetic mutations split equally between GPIIb and GPIIIa. Some cases are suspected to be transmitted as an autosomal dominant trait. Glycoproteins play a major role in platelet functioning, as it is part of the membrane receptors indispensable for platelet aggregation and interaction with fibrinogen.

This medical condition was first described in 1918 by Eduard Glanzmann (1887–1959) and Otto Nägeli (1871–1938).

In most patients, the diagnosis of GT is made in childhood, and in some cases shortly after birth, with the presence of purpura in places of pressure during natural childbirth. The laboratory criteria for diagnosis include normal platelet count and morphology, prolonged bleeding time, marked absence or decrease in platelet aggregation in response to ADP, collagen and epinephrine, but normal for ristocetin, and study of normal plasma coagulation. In the clinical presentation of the disease, haemorrhagic signs (particularly mucocutaneous) occur, such as purpura, gingival haemorrhage, menorrhagia and mainly epistaxis. The severity of the bleeding is variable. The most serious episodes are the result of trauma or exacerbation of physiological bleeding. Menarche represents a risky situation, the same occurring with pregnancy and childbirth of patients with the disease. Clinical manifestations tend to decrease with adulthood. GT is rare with low incidence rates among the general population (1:1,000,000), but it can become frequent in racial groups where consanguineous marriages occur. 

The expression of GPIIb/IIIa on the platelet surface detected under flow cytometry determine three subtypes of GT. These are type I (GPIIb/IIIa 5 % or less), type II (GPIIb/IIIa 5–20 %) variant or type III (GPIIb/IIIa >20 % to normal, normal levels of integrin, but the protein is nonfunctional).

The standard treatment of haemorrhagic episodes and their prevention is platelet transfusion. This measure is generally effective, although alloimmunisation subsequently limits the average life of the infused platelets leading to platelet refractoriness. The alternative is recombinant activated factor VII (rFVIIa) currently approved in the EU for GT patients with platelet antibodies and past or present history of refractoriness to platelet transfusion, or when platelets are not readily available. 

An acquired form of GT is also seen which is caused by antibodies to platelet integrin αIIbβ3. These patients have a low platelet count with a moderate-to-severe bleeding tendency, while some patients may have normal platelet counts. It is commonly found in association with autoimmune disorders, haematological malignancies, and infections. Acquired GT may also result from taking GPIIb/IIIa inhibitory medications (e.g., abciximab, eptifibatide, or tirofiban).