Glanzmann's thrombasthenia overview
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Glanzmann's thrombasthenia |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Niyousha Danesh, M.D., MPH.
Overview
Glanzmann's thrombasthenia is an extremely rare autosomal recessive bleeding syndrome affecting the megakaryocyte lineage, in which the platelets lack glycoprotein IIb/IIIa (ITG αIIbβ3), [1] either qualitative or quantitative. Hence, no fibrinogen bridging can occur, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes.
GT is associated with clinical variability: some patients have only minimal bruising while others have frequent, severe and potentially fatal hemorrhages. The site of bleeding in GT is clearly defined: purpura, epistaxis, gingival bleeding, and menorrhagia are nearly constant features; gastrointestinal bleeding and hematuria are less common. In most cases, bleeding symptoms manifest rapidly after birth, even if GT is occasionally only diagnosed in later life. Diagnosis should be suspected in patients with mucocutaneous bleeding with absent platelet aggregation in response to all physiologic stimuli, and a normal platelet count and morphology. [2] Bleeding time is also significantly prolonged in this disease.
Historical Perspective
In 1918, Eduard Glanzmann, a Swiss pediatrician, first described this disease.[1]
In 1956, Braunsteiner and Pakesch reviewed disorders of platelet function and described thrombasthenia as an inherited disease characterized by platelets of normal size that failed to spread onto the surface and did not support clot retraction.
In 1964 the diagnostic features of GT, including the absence of platelet aggregation as the primary feature were clearly established by the classic report on 15 French patients by Caen et al.
Those patients with absent platelet aggregation and absent clot retraction were subsequently termed as having type I disease; those with absent aggregation but residual clot retraction, type II disease; while variant disease was first established in 1987.[2]
Classification
Glanzmann thrombasthenia (GT) is classified in to two types : hereditary GT, which is sub classified into 3 types,( type I
, II and III ) and acquired GT.
Hereditary GT
Glanzmann thrombasthenia (GT) is an autosomal recessive inherited qualitative platelet disorder characterized by absence or reduction of platelet glycoprotein GPIIb or GPIIIa. CD61, Glanzmann thrombasthenia is classified into three types :
Patients with less than 5% of normal GPIIb/IIIa are classified as type I
Type II variants have 5% to 20% normal GPIIb/IIIa .
And Type III patients possess near-normal GPIIb/ IIIa levels but dysfunctional receptors.
these classification is according to clot retraction and platelet fibrinogen content [3]
These subtypes vary based on ethnicity . For example Type I GT is found commonly in Arabs and Iraqi-Jews living in Israel, whilst type II GT is relatively frequent in the Japanese population.[4]
GT has also another subtype named as Variant GT, this group includes patients with platelets expression of αIIbβ3 more than 20% in which mainly the platelets are able to aggregate but they present the clinical phenotype of GT. The principal reason is that the stimulated platelets can not bind to soluble Fg or antibodies recognizing activation-dependent determinants on αIIbβ3. T It is commonly due to substitutions in single amino acid . [5]
Acquired GT
Acquired GT is defined by inhibition of platelet αIIbβ3 actual function due to the attack of autoantibodies. These antibodies can be produced in numerous disorders such as hematologic malignancy, transfusion, drugs and autoimmune diseases.
Pathophysiology
Glanzmann's thrombasthenia is an autosomal recessive hematologic disorder . Megakaryocyte lineage is affected in this disease, and leads to dysfunctional platelet aggregation.The pathogenesis is related to a quantitative and/or qualitative defect in GpIIb/IIIa (αIIbβ3 integrin) construction. This receptor mediates platelet aggregation and thrombus formation when the blood vessel is damaged.
The GpIIb/IIIa is an adhesion receptor and is expressed in platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen and thrombin. The GpIIb/IIIa integrin is essential to the blood coagulation since it has the ability to bind fibrinogen, the von Willebrand factor, fibronectin and vitronectin. This enables the platelet to be activated by contact with the collagen-von Willebrand-complex that is exposed when the endothelial blood vessel lining is damaged and then aggregate with other thrombocytes via fibrinogen.
Patients suffering from Glanzmann's thrombasthenia thus have platelets less able to adhere to each other and to the underlying tissue of damaged blood vessels.
Integrin (ITG) αIIbβ3 has roll in platelet aggregation and adhesion, connection between cells, cell migration and thrombus formation.
Causes
Differentiating Glanzmann's thrombasthenia overview from Other Diseases
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References
- ↑ 1.0 1.1 Solh T, Botsford A, Solh M (2015). "Glanzmann's thrombasthenia: pathogenesis, diagnosis, and current and emerging treatment options". J Blood Med. 6: 219–27. doi:10.2147/JBM.S71319. PMC 4501245. PMID 26185478.
- ↑ 2.0 2.1 Nurden AT (2006). "Glanzmann thrombasthenia". Orphanet J Rare Dis. 1: 10. doi:10.1186/1750-1172-1-10. PMC 1475837. PMID 16722529.
- ↑ Arimura H (1975). "Correlation between molecular size and interferon- inducing activity of poly I:C". Acta Virol. 19 (6): 457–66. PMID 1990;75:1383–95 Check
|pmid=value (help). - ↑ Kannan M, Ahmed RP, Jain P, Kumar R, Choudhry VP, Saxena R (2003). "Type I Glanzmann thrombasthenia: most common subtypes in North Indians". Am J Hematol. 74 (2): 139–41. doi:10.1002/ajh.10395. PMID 14508803.
- ↑ Nurden AT, Pillois X, Wilcox DA (2013). "Glanzmann thrombasthenia: state of the art and future directions". Semin Thromb Hemost. 39 (6): 642–55. doi:10.1055/s-0033-1353393. PMC 4011384. PMID 23929305.