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Glanzmann's thrombasthenia
Glanzmann's thrombasthenia
Other names	Thrombasthenia of Glanzmann and Naegeli
	This condition is inherited in a autosomal recessive manner
Specialty	Hematology

Glanzmann's thrombasthenia is an abnormality of the platelets.^[2] 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:^[3]

heavy menstrual bleeding
easy bruising
nosebleeds
Bleeding from the gums
gastrointestinal bleeding
postpartum bleeding
increased postoperative bleeding.

The bleeding tendency is variable but may be severe. Bleeding into the joints, particularly spontaneous bleeds, are 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.^{[citation needed]}

Cause

Glanzmann's thrombasthenia can be inherited in an autosomal recessive manner^[3]^[4] or acquired as an autoimmune disorder.^[3]^[5]

The bleeding tendency in Glanzmann's thrombasthenia is variable,^[3] some individuals having minimal bruising, while others have frequent, severe, potentially fatal hemorrhages. Moreover, platelet α_IIbβ₃ levels correlate poorly with hemorrhagic severity, as virtually undetectable α_IIbβ₃ levels can correlate with negligible bleeding symptoms, and 10%–15% levels can correlate with severe bleeding.^[6] Unidentified factors other than the platelet defect itself may have important roles.^[3]

Pathophysiology

Glanzmann's thrombasthenia is associated with abnormal integrin α_IIbβ₃, formerly known as glycoprotein IIb/IIIa (GpIIb/IIIa),^[7] 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).^{[citation needed]} 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.^[4]^[8]

Diagnosis

Light transmission aggregometry is widely accepted as the gold standard diagnostic tool for assessing platelet function, and a result of absent aggregation with any agonist except ristocetin is highly specific for Glanzmann's thrombasthenia.^[9] Following is a table comparing its result with other platelet aggregation disorders:

Platelet aggregation function by main disorders and agonists edit
Further information: Platelet § Tests of function
	ADP	Epinephrine	Collagen	Ristocetin
P2Y receptor inhibitor or defect^[10]	Decreased	Normal	Normal	Normal
Adrenergic receptor defect^[10]	Normal	Decreased	Normal	Normal
Collagen receptor defect^[10]	Normal	Normal	Decreased or absent	Normal
Von Willebrand disease (except Type 2B) Bernard–Soulier syndrome^[10]	Normal	Normal	Normal	Decreased or absent
Glanzmann's thrombasthenia^[10]	Decreased	Decreased	Decreased	Normal or decreased

Treatment

Therapy involves both preventive measures and treatment of specific bleeding episodes.^[3]

Dental hygiene lessens gingival bleeding^[11]
Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and anticoagulants
Iron or folate supplementation may be necessary if excessive or prolonged bleeding has caused anemia
Hepatitis B vaccine
Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic acid (Amicar)
Desmopressin (DDAVP) does not normalize the bleeding time in Glanzmann's thrombasthenia but anecdotally improves hemostasis
Hormonal contraceptives to control excessive menstrual bleeding
Topical agents such as gelfoam, fibrin sealants, polyethylene glycol polymers, custom dental splints
Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization)
Recombinant factor VIIa, AryoSeven or NovoSeven FDA approved this drug for the treatment of the disease in July 2014.
Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages

Eponym

It is named after Eduard Glanzmann (1887–1959), the Swiss pediatrician who originally described it.^[12]^[13]^[14]

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 Caen^[15] and Phillips and colleagues^[16] discovered that thrombasthenic platelets are deficient in integrins α_IIbβ_3.

References

^ "Glanzmann thrombasthenia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 30 October 2019. Retrieved 30 October 2019.
^ "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, Uri (2002). "Glanzmann thrombasthenia: a model disease which paved the way to powerful therapeutic agents". Pathophysiology of Haemostasis and Thrombosis. 32 (5–6): 216–7. doi:10.1159/000073569. PMID 13679645.
^ 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. doi:10.1111/j.1365-2141.2004.05173.x. PMID 15461628. S2CID 33436277.
^ Nurden, Alan T (2006). "Glanzmann thrombasthenia". Orphanet Journal of Rare Diseases. 1: 10. doi:10.1186/1750-1172-1-10. PMC 1475837. PMID 16722529.
^ Nurden, A. T.; Fiore, M.; Nurden, P.; Pillois, X. (2011). "Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models". Blood. 118 (23): 5996–6005. doi:10.1182/blood-2011-07-365635. PMID 21917754.
^ "Glanzmann Thrombasthenia Workup: Laboratory Studies, Histologic Findings".
^ Solh, Melhem; Solh, Tia; Botsford, Ashley (2015). "Glanzmann's thrombasthenia: pathogenesis, diagnosis, and current and emerging treatment options". Journal of Blood Medicine. 6: 219–227. doi:10.2147/JBM.S71319. ISSN 1179-2736. PMC 4501245. PMID 26185478.
^ ^a ^b ^c ^d ^e Borhany, Munira; Pahore, Zaen; ul Qadr, Zeeshan; Rehan, Muhammad; Naz, Arshi; Khan, Asif; Ansari, Saqib; Farzana, Tasneem; Nadeem, Muhammad; Raza, Syed Amir; Shamsi, Tahir (2010). "Bleeding disorders in the tribe: result of consanguineous in breeding". Orphanet Journal of Rare Diseases. 5 (1). doi:10.1186/1750-1172-5-23. ISSN 1750-1172. PMID 20822539.
^ 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. 15 (2): 152–165. doi:10.1177/1076029608326165. PMID 18930954. S2CID 25455222.
^ Nurden AT, Caen JP (1974). "An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia". British Journal of Haematology. 28 (2): 253–260. doi:10.1111/j.1365-2141.1974.tb06660.x. PMID 4473996. S2CID 39906589.
^ Phillips DR, Jenks CS, Luscher EF, Larrieu M (1975). "Molecular differences of exposed surface proteins on thrombasthenic platelet plasma membrane". Nature. 257 (5527): 599–600. Bibcode:1975Natur.257..599P. doi:10.1038/257599a0. PMID 1172605. S2CID 4188393.{{cite journal}}: CS1 maint: multiple names: authors list (link)