Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/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:
The bleeding tendency is variable but may be severe. Hemarthrosis, particularly spontaneous, is very rare, in contrast to the hemophilias.
Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin, but impaired with other agonists such as ADP, thrombin, collagen or epinephrine.
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 hemorrhage. Unidentified factors other than the platelet defect itself may have important roles.
Glanzmann's thrombasthenia is associated with abnormal glycoprotein IIb/IIIa (GpIIb/IIIa), also known as αIIbβ3, 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 (as well as von Willebrand factor, fibronectin, and vitronectin), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation).
In contrast, glycoprotein Ib 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.
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.
Therapy involves both preventive measures and treatment of specific bleeding episodes.
It is named after Eduard Glanzmann (1887-1959), the Swiss pediatrician who originally described it.
- ^ "Glanzmann thrombasthenia" at Dorland's Medical Dictionary
- ^ a b c d e f Kaushansky K, Lichtman M, Beutler E, Kipps T, Prchal J, Seligsohn U. (2010; edition 8: pages 1933-1941) Williams Hematology. McGraw-Hill.ISBN 978-0071621519
- ^ a b Seligsohn U (2002). "Glanzmann thrombasthenia: a model disease which paved the way to powerful therapeutic agents" (PDF). Pathophysiol. Haemost. Thromb. 32 (5-6): 216–7. PMID 13679645. doi:10.1159/000073569.
- ^ Tholouli E, Hay CR, O'Gorman P, Makris M (2004). "Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder". Br. J. Haematol. 127 (2): 209–13. PMID 15461628. doi:10.1111/j.1365-2141.2004.05173.x.
- ^ Nurden, A. T. (2006). "Glanzmann thrombasthenia". Orphanet Journal of Rare Diseases 1: 10. PMC 1475837. PMID 16722529. doi:10.1186/1750-1172-1-10.
- ^ F.Z. Elmouatarif, B. Badre, S. Elarabi (2013). "Thrombasthénie de Glanzmann". Le courrier du dentiste.
- ^ synd/1289 at Who Named It?
- ^ Glanzmann, WE (1918). "Hereditäre hämorrhagische Thrombasthenie. Ein Beitrag zur Pathologie der Blutplättchen.[Hereditary haemorrhagic thrombasthenia. A contribution to the pathology of platelets] (German)". Jahrbuch für Kinderheilkunde [Yearbook of Pediatrics] 88 (1-42): 113–141.
- ^ Kannan, M.; Saxena, R. (2009). "Glanzmann's thrombasthenia: an overview". Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 15 (2): 152–165. PMID 18930954. doi:10.1177/1076029608326165.
- Internet database of mutations giving rise to Glanzmann's thrombasthenia: