Role of platelets in the pathogenesis of antiphospholipid syndrome
DOI:
https://doi.org/10.15305/ijrci/v1i1/21Keywords:
antiphospholipid syndrome, platelet activation, platelet degranulationAbstract
Aim
To delineate the role of platelets in thrombotic process in APS patients.
Background
Pathogenesis of APS is an ongoing area of research and studying the role of platelets will be helpful in developing newer diagnostic and therapeutic strategies.
Materials and methods
Forty patients with APS, diagnosed as per modified 2006 Sapporo’s Criteria and who were not on aspirin or any other antiplatelet drug, were included. The same number of age- and sex-matched healthy controls was also recruited for comparison. The following platelet function studies were performed using the blood samples collected from APS patients as well as healthy controls: platelet aggregation studies, platelet secretion of dense granules (a. total degranulation b. platelet secretion of granules in relation to time c. visualization of platelet degranulation), clot retraction studies, and western blot studies on clot retracted samples for demonstration of activated proteomes.
Results
A significant increase (P < 0.001) in the platelet aggregation in APS patients as compared to healthy controls was noted. The subjects also showed a significant increase (P < 0.05) in the platelet granule release as well as more degranulation (P < 0.001) in relation to time at stored condition, which were well-visualized under phase-contrast microscope. Sixty-five percent of APS patients showed lesser as well as delayed clot retraction as compared to healthy controls, signifying that the platelet clots are less retractile in APS patients.
Conclusion
The study clearly demonstrates the hyperactivity of platelets in APS patients in each step of their activation as compared to the controls. This indicates the major role played by platelets in APS pathogenesis.
References
Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346(10):752–63.
Alarcon-Segovia D, Deleze M, Oria CV, et al.. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients. Medicine (Baltimore). 1989; 68(6): 353-65.
Arnold J, Holmes Z, Pickering W, Farmer C, Regan L, Cohen H. Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage. Br J Haematol 2001; 113(4):911–14.
Rand JH, Wu XX, Andree HA, Lockwood CJ, Guller S, Scher J, et al.. Pregnancy loss in the antiphospholipid-antibody syndrome—a possible thrombogenic mechanism. N Engl J Med 1997; 337(3):154–60.
Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelisms with heparin-induced thrombocytopenia. Thromb Haemost. 1996; 75(4): 536-41.
Forastiero R, Martinuzzo M, Carreras LO, Maclouf J. Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. Thromb Haemost 1998; 79 (1): 42–45.
Galli M, Cortelazzo S, Viero P, Finazzi G, de Gaetano G, Barbui T. Interaction between platelets and lupus anticoagulant. Eur J Haematol 1988; 41(1): 88–94.
Fanelli A, Bergamini C, Rapi S, Caldini A, Spinelli A, Buggiani A & Emmi L. Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies. Lupus 1997; 6(3): 61-67.
Miyakis S, Lockshin MD, Atsumi T, et al.. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4(2):295–306.
Shrivastava S, Bera T, Singh SK, Singh G, Ramachandrarao P, Dash D. Characterization of Antiplatelet Properties of Silver Nanoparticles. ACS Nano. 2009;3(6): 1357-64.
Law DA, DeGuzman FR, Heiser P, et al.. Integrin cytoplasmic tyrosine motif is required for outside-in IIb3 signalling and platelet function. Nature. 1999;401(6755):808-11.
Osdoit S, Rosa JP. Fibrin clot retraction by human platelets correlates with IIb3 integrin-dependent protein tyrosine dephosphorylation. J Biol Chem. 2001; 276: 6703-10.
Podolnikova NP, Yakubenko VP, Volkov G L, Plow EF, Ugarova TP. Identification of a Novel Binding Site for Platelet Integrin _IIb_3 (GPIIbIIIa) and α5β1 in the ϒCDomain of Fibrinogen. J. Biol. Chem. 2003; 278: 32251-58.
Stenberg PE, Mc Ever RP, Shuman MA, Jacques YV, Bainton DF. A platelet al.pha-granule membrane protein (GMP- 140) is expressed on the plasma membrane after activation. Journal of Cell Biolog. 1985; 101(3): 880-86.
Berman CL, Yeo EL, Wencel-Drake J, Furie BC, Ginsberg MH, Furie B. A platelet al.pha-granule protein that is associated with the plasma membrane after activation: characterization and subcellular localisation of platelet-activation dependent granule-external membrane protein. Journal of Clinical Investigation. 1986;78: 130-37.
Nishibori M, Cham B, McNicol A, Shalev A, Jain N, Gerrard JM. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky±Pudlak syndrome, and appears identical to granulophysin. Journal of Clinical Investigation.1993; 91(4): 1775-82.
Joseph JE, Donohoe S, Harrison P, Mackie I.J, Machin SJ. Platelet activation and turnover in the primary antiphospholipid syndrome. Lupus.1998; 7(5): 333-40.
Urbanus RT, Derksen RH, de Groot PG. Platelets and the antiphospholipid syndrome. Lupus 2008; 17(10):888.
Shi T, Giannakopoulos B, Yan X, et al.. Anti-beta2-glycoprotein I antibodies in complex with beta2-glycoprotein I can activate platelets in a dysregulated manner via glycoprotein Ib-IX-V. Arthritis Rheum 2006; 54(8): 2558-67.
Wiener HM, Vardinon N, Yust I. Platelet antibody binding and spontaneous aggregation in 21 lupus anticoagulant patients. Vox Sanguinis.1991; 61(2):111-21.
Siess W. Molecular mechanisms of platelet activation. Physiol Rev. 1989; 69(1):58-178.
Fox JE. The platelet cytoskeleton. Thromb Haemost. 1993; 70(6):884-93.
Zucker-Franklin D. In Greaves MF, Grossi CE, Marmot AM, Zucker-Franklin D (eds). Atlas of Blood Cells, Function, and Pathology. Vol. 2. Philadelphia: Lea & Febiger, 1988.
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