Glanzmann's thrombasthenia
| Glanzmann's thrombasthenia | |
|---|---|
| Classification and external resources | |
| Specialty | hematology |
| ICD-10 | D69.1 |
| ICD-9-CM | 287.1 |
| OMIM | 187800 273800 |
| DiseasesDB | 5224 |
| MedlinePlus | 001305 |
| eMedicine | med/872 |
| MeSH | D013915 |
Glanzmann's thrombasthenia is an abnormality of the platelets.[1] 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:[2]
- menorrhagia
- easy bruising
- epistaxis
- gingival bleeding
- gastrointestinal bleeding
- postpartum bleeding
- increased bleeding post-operatively.
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.
Cause
Glanzmann's thrombasthenia can be inherited in an autosomal recessive manner[2][3] or acquired as an autoimmune disorder.[2][4]
The bleeding tendency in Glanzmann's thrombasthenia is variable,[2] 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.[5] Unidentified factors other than the platelet defect itself may have important roles.[2]
Pathophysiology
Glanzmann's thrombasthenia is associated with abnormal integrin αIIbβ3, formerly known as glycoprotein IIb/IIIa (GpIIb/IIIa),[6] 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, 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.[3]
Treatment
Therapy involves both preventive measures and treatment of specific bleeding episodes.[2]
- Dental hygiene lessens gingival bleeding[7]
- 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 on July 2014.
- Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages
Eponym
It is named after Eduard Glanzmann (1887-1959), the German pediatrician who originally described it.[8][9][10]
See also
References
- ↑ "Glanzmann thrombasthenia" at Dorland's Medical Dictionary
- 1 2 3 4 5 6 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
- 1 2 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.
- ↑ 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.
- ↑ 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.