Glanzmann's thrombasthenia laboratory findings
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Glanzmann's thrombasthenia |
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Differentiating Glanzmann's thrombasthenia from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]
Overview
Glanzmann's thrombasthenia is commonly mistaken with other acquired platelet disorders , while they have similar clinical and laboratory presentations, such as epistaxis, easily bruising or heavy menstruation or severe bleeding after minor trauma ,hence the diagnosis of GT begins with the aforementioned symptoms, family history of consanguineous marriage and the clinical presentation (petechia, purpura, ecchymoses,...).
Routine laboratory tests after these symptoms are not generally diagnostic , since the complete blood count (CBC) can be completely normal. The platelet count in Glanzmann's thrombasthenia is usually normal (mostly on the lower end of normal), as in GT the quality of the platelet is disordered,not the quantity. The red blood cell count may be normal or reveal anemia due to bleeding.
The prolonged bleeding time warns the potential of GT, however the activated partial thromboplastin (PTT) and prothrombin time (PT) are in this disease usually normal.
Flow cytometry is also useful .In flow cytometry various monoclonal antibodies are used for measuring different platelet receptor densities. Since the glycoprotein receptor in Glanzmann's thrombasthenia is dysfunctional or deficient.
Among the patients with GT in flow cytometric analysis the αIIbβ3 is nonfunctional or deficient, CD41 and CD61 markers are absent or reduced, but the levels of CD42 is normal.
Other beneficial test for Glanzmann's thrombasthenia diagnosis is platelet function analyzer (PFA-100) study. This test is highly sensitive and it is prolonged in patients with GT.
In PFA-100 study a destructed vessel endothelium is simulated by using cartridges of collagen + implanted epinephrine and collagen + ADP . When the citrated whole blood moves along these cartridges with high shear stress rate ,the platelets adhere and a platelet plug is manufactured.
The most accurate method of GT diagnose is Genomic DNA analysis. in which the mutation in sequence of the 45 exons containing the αIIbβ3 unit is investigated, accompanied by the splice spots of the ITGA2B and ITGB3 gene. Moreover second DNA sample analysis is mandatory for the the confirmation of diagnosis.
Light transmission aggregometry (LTA) is highly specific for diagnosis of Glanzmann's thrombasthenia . In this test a platelet agonist is added to the centrifuged platelet-rich plasma samples and they are observed before and after the addition of the agonist.
The agonists include : ADP, ristocetin, arachidonic acid, collagen, thromboxane A2 mimetic, thrombin receptor activating peptide and epinephrine.
This test assesses mainly the platelet aggregation, specifically the percent of aggregation, the slope of aggregation, deaggregation, shape changes and the lag phase are investigated . Through LTA platelet aggregation is disturbed with any agonist, other than ristocetin, in which the reaction is preserved.
LTA is greatly acknowledged as the gold standard diagnostic method for platelet function assessment. Although it is a very accurate test but it is personnel dependent and requires a lot of time consuming, moreover experienced laboratories are needed.
Another inconvenience of LTA assessment is among pediatric patients and thrombocytopenic patients, as obtaining platelet-rich plasma is difficult in them.
All in all the diagnosis of Glanzmann's thrombasthenia is through the prolonged bleeding time, normal platelet count and prolonged PFA time in blood tests. Platelets aggregation failure in LTA with all agonists except ristocetin is diagnostic of GT. [1]
Laboratory Findings
CBC and peripheral smear examination
Initial evaluation of a patient for a suspected functional platelet disorder should include a complete blood count and examination of the peripheral blood smear. The red blood cell count (CBC) is usually normal. Some patients with Glanzmann's thrombasthenia may have reduced count of red blood cell, because of coexisting iron deficiency or bleeding. The platelet count in Glanzmann's thrombasthenia is mostly on the lower end of normal.[2][3]
Thromboplastin (PTT) and Prothrombin time (PT)
The activated partial thromboplastin (PTT) and prothrombin time (PT) are in this disease commonly normal.[4][5]
Platelet aggregation assays
Platelet aggregation assays which is panel of assays measuring platelet aggregation and activation in vitro. using like ADP, arachidonic acid, collagen, epinephrine, thrombin, and ristocetin. [6][7]
Automated platelet function screening tests
There are several newer technologies in current clinical use measuring various aspects of platelet function.[8][9][10][11][12]
Platelet Function Analyzer (PFA-100)
The most widely tested is the PFA-100 device. It is used to distinguish between an aspirin-induced defect and more severe platelet dysfunction [8][9][10][11][12][13][14].Platelets aggregation failure in LTA with all agonists except ristocetin is diagnostic of Glanzmann's thrombasthenia. Laboratory findings consistent with the diagnosis of Glanzmann's thrombasthenia include prolonged bleeding time (BT) and failure of platelets plugging to the collagen-based filter in the PFA-100 test.
The diagnosis of Glanzmann thrombasthenia is confirmed through monoclonal antibody testing and Flow cytometry. The coagulation tests and platelet count are usually normal among patients with Glanzmann's thrombasthenia. The platelet morphology on peripheral blood smears is normal in patients with Glanzmann's thrombasthenia. [5] [4]
References
- ↑ Fiore M, Nurden AT, Nurden P, Seligsohn U (2012). "Clinical utility gene card for: Glanzmann thrombasthenia". Eur J Hum Genet. 20 (10). doi:10.1038/ejhg.2012.151. PMC 3449071. PMID 22781097.
- ↑ Gunay-Aygun M, Zivony-Elboum Y, Gumruk F, Geiger D, Cetin M, Khayat M, Kleta R, Kfir N, Anikster Y, Chezar J, Arcos-Burgos M, Shalata A, Stanescu H, Manaster J, Arat M, Edwards H, Freiberg AS, Hart PS, Riney LC, Patzel K, Tanpaiboon P, Markello T, Huizing M, Maric I, Horne M, Kehrel BE, Jurk K, Hansen NF, Cherukuri PF, Jones M, Cruz P, Mullikin JC, Nurden A, White JG, Gahl WA, Falik-Zaccai T (December 2010). "Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p". Blood. 116 (23): 4990–5001. doi:10.1182/blood-2010-05-286534. PMC 3012593. PMID 20709904.
- ↑ Drouin A, Favier R, Massé JM, Debili N, Schmitt A, Elbim C, Guichard J, Adam M, Gougerot-Pocidalo MA, Cramer EM (September 2001). "Newly recognized cellular abnormalities in the gray platelet syndrome". Blood. 98 (5): 1382–91. PMID 11520786.
- ↑ 4.0 4.1 Nurden AT (April 2006). "Glanzmann thrombasthenia". Orphanet J Rare Dis. 1: 10. doi:10.1186/1750-1172-1-10. PMC 1475837. PMID 16722529.
- ↑ 5.0 5.1 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.
- ↑ Quiroga T, Goycoolea M, Matus V, Zúñiga P, Martínez C, Garrido M, Aranda E, Leighton F, Panes O, Pereira J, Mezzano D (December 2009). "Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays". Br. J. Haematol. 147 (5): 729–36. doi:10.1111/j.1365-2141.2009.07890.x. PMID 19775303.
- ↑ Jennings I, Woods TA, Kitchen S, Walker ID (August 2008). "Platelet function testing: practice among UK National External Quality Assessment Scheme for Blood Coagulation participants, 2006". J. Clin. Pathol. 61 (8): 950–4. doi:10.1136/jcp.2008.057174. PMID 18663056.
- ↑ 8.0 8.1 Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti ML (November 1999). "Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion". Thromb. Res. 96 (3): 213–7. PMID 10588464.
- ↑ 9.0 9.1 Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, Larkin EC, Liles D, Nugent DJ (1998). "PFA-100 system: a new method for assessment of platelet dysfunction". Semin. Thromb. Hemost. 24 (2): 195–202. doi:10.1055/s-2007-995840. PMID 9579642.
- ↑ 10.0 10.1 Jilma B (September 2001). "Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction". J. Lab. Clin. Med. 138 (3): 152–63. doi:10.1067/mlc.2001.117406. PMID 11528368.
- ↑ 11.0 11.1 Favaloro EJ (March 2001). "Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations". Haemophilia. 7 (2): 170–9. PMID 11260277.
- ↑ 12.0 12.1 Harrison P (December 2000). "Progress in the assessment of platelet function". Br. J. Haematol. 111 (3): 733–44. PMID 11122132.
- ↑ Hayward CP, Pai M, Liu Y, Moffat KA, Seecharan J, Webert KE, Cook RJ, Heddle NM (April 2009). "Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments". J. Thromb. Haemost. 7 (4): 676–84. doi:10.1111/j.1538-7836.2009.03273.x. PMID 19143930.
- ↑ BORN GV (June 1962). "Aggregation of blood platelets by adenosine diphosphate and its reversal". Nature. 194: 927–9. PMID 13871375.