Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy, in which the platelets contain defective or low levels of glycoprotein IIb/IIIa, which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
Signs and symptoms
Characteristically, there is increased mucosal bleeding:
Glanzmann's thrombasthenia can be inherited in an autosomal recessive manner or acquired as an autoimmune disorder. The bleeding tendency in Glanzmann's thrombasthenia is variable, some individuals having minimal bruising, while others have frequent, severe, potentially fatal hemorrhages. Moreover, platelet αIIbβ3 levels correlate poorly with hemorrhagic severity, as virtually undetectable αIIbβ3 levels can correlate with negligible bleeding symptoms, and 10%–15% levels can correlate with severe bleeding. Unidentified factors other than the platelet defect itself may have important roles.
Pathophysiology
Glanzmann's thrombasthenia is associated with abnormal integrin αIIbβ3, formerly known as glycoprotein IIb/IIIa, which is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen, which is required for fibrinogen-dependent platelet-platelet interaction.In contrast, glycoproteinIb receptors are normal with Glanzmann's thrombasthenia. The role of GpIb is to enable platelet activation by contact with the von Willebrand factor-collagen complex that is exposed when the endothelial blood vessel lining is damaged. GpIb receptors are deficient in a disease known as Bernard–Soulier syndrome. Understanding of the role of GpIIb/IIIa in Glanzmann's thrombasthenia led to the development of GpIIb/IIIa inhibitors, a class of powerful antiplatelet agents.
Treatment
Therapy involves both preventive measures and treatment of specific bleeding episodes.
It is named after Eduard Glanzmann, the Swiss pediatrician who originally described it.
History
The subsequent studies, following Eduard Glanzmann’s description of hemorrhagic symptoms and “weak platelets” demonstrated that these patients have prolonged bleeding times and their platelets failed to aggregate in response to activation.In the mid 1970s Nurden and Caenand Phillips and colleaguesdiscovered that thrombasthenic platelets are deficient in integrins αIIbβ3.
