Sticky Platelet Syndrome: 35 Years of Growing Evidence

Peter Kubisz; Pavol Holly; Jan Stasko

doi:10.1055/s-0038-1676581

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2019; 45(01): 061-068
DOI: 10.1055/s-0038-1676581

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sticky Platelet Syndrome: 35 Years of Growing Evidence

Peter Kubisz

¹Department of Haematology and Transfusion Medicine, National Centre of Haemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, Martin, Slovakia

,

Pavol Holly

¹Department of Haematology and Transfusion Medicine, National Centre of Haemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, Martin, Slovakia

,

Jan Stasko

¹Department of Haematology and Transfusion Medicine, National Centre of Haemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, Martin, Slovakia

› Author Affiliations

Abstract

Since the identification of antithrombin deficiency by Egeberg in 1956, ongoing research in prothrombotic defects continues to progress. Interestingly, past research has predominantly focused on coagulation factors and not on other components of the hemostatic system. The possible role of platelet function defects in the development of thrombotic events was suggested for the first time in the late 1970s, when an increased platelet adhesiveness and aggregation after epinephrine (EPI) and adenosine diphosphate (ADP) was found in a group of patients with unexplained transient ischemic attack. Clinical evidence for other types of thrombotic events (e. g. myocardial infarction, ischemic stroke, optic neuropathy, and pregnancy-related complications) with similar laboratory findings was provided by several authors in the 1980s and 1990s, with Drs. Mammen and Bick undertaking key research. The familial occurrence was noted as well, and the term sticky platelet syndrome was introduced by Holliday in 1983 to describe the defect. The term in our present understanding describes a thrombophilic qualitative platelet disorder characterized by increased in vitro platelet aggregation after the addition of very low concentrations of ADP and/or EPI and an increased risk of thromboembolic (predominantly arterial) events. Although now recognized for 35 years, significant issues, namely its etiology, inheritance, epidemiology, and diagnostics, remain a matter of vigorous debate. The aim of this review is to summarize the history, key works, and present understanding of the syndrome and to outline present-day diagnostic and clinical problems and controversies.

Keywords

sticky platelet syndrome - platelet hyperaggregability - thrombophilia - platelet disorders - adenosine diphosphate - epinephrine

Full Text

References

References
1 Raskob GE, Angchaisuksiri P, Blanco AN. , et al; ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost 2014; 40 (07) 724-735
2 Secemsky EA, Rosenfield K, Kennedy KF, Jaff M, Yeh RW. High burden of 30-day readmissions after acute venous thromboembolism in the United States. J Am Heart Assoc 2018; 7 (13) e009047
3 Moustafa A, Alim HM, Chowdhury MA, Eltahawy EA. Postthrombotic syndrome: long-term sequela of deep venous thrombosis. Am J Med Sci 2018; 356 (02) 152-158
4 Bizzozero J. Über einen neuen Formbestandteil des Blutes und dessen Rolle bei der Thrombose und der Blutgerinnung. Virchow's. Arch Pathol Anat Physiol Klin Med 1882; 90: 261-332
5 Osler W. On certain problems in the physiology of the blood corpuscles. The Medical News 1886; 48: 421-425
6 Coller BS. Historical perspective and future directions in platelet research. J Thromb Haemost 2011; 9 (Suppl. 01) 374-395
7 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
8 O'Brien J. Platelet aggregation: part II Some results from a new method of study. J Clin Pathol 1962; 15 (05) 452-455
9 ten Cate JW, Vos J, Oosterhuis H, Prenger D, Jenkins CS. Spontaneous platelet aggregation in cerebrovascular disease. Thromb Haemost 1978; 39 (01) 223-229
10 al-Mefty O, Marano G, Raiaraman S, Nugent GR, Rodman N. Transient ischemic attacks due to increased platelet aggregation and adhesiveness. Ultrastructural and functional correlation. J Neurosurg 1979; 50 (04) 449-453
11 Holiday PL, Mammen E, Gilroy J. Sticky platelet syndrome and cerebral infarction in young adults. Paper presented at the 9th International Joint Conference on Stroke and Cerebral Circulation, Phoenix, AZ, 1983
12 Mammen EF. Ten years' experience with the “sticky platelet syndrome.”. Clin Appl Thromb Hemost 1995; 1: 66-72
13 Rubenfire M, Blevins RD, Barnhart M, Housholder S, Selik N, Mammen EF. Platelet hyperaggregability in patients with chest pain and angiographically normal coronary arteries. Am J Cardiol 1986; 57 (08) 657-660
14 Mammen EF, Barnhart MI, Selik NR, Gilroy J, Klepach GL. “Sticky platelet syndrome”: a congenital platelet abnormality predisposing to thrombosis?. Folia Haematol Int Mag Klin Morphol Blutforsch 1988; 115 (03) 361-365
15 Mammen EF. Sticky platelet syndrome. Semin Thromb Hemost 1999; 25 (04) 361-365
16 Frenkel EP, Mammen EF. Sticky platelet syndrome and thrombocythemia. Hematol Oncol Clin North Am 2003; 17 (01) 63-83
17 Bick RL. Sticky platelet syndrome: a common cause of unexplained arterial and venous thrombosis. Clin Appl Thromb Hemost 1998; 4: 77-81
18 Warrier I, Nigro M, Hillman C. , et al. Platelet activation associated with stroke migraine in children. Thromb Haemost 1991; 65: 772
19 Berg-Dammer E, Henkes H, Trobisch H, Kühne D. Sticky platelet syndrome: a cause of neurovascular thrombosis and thrombo-embolism. Interv Neuroradiol 1997; 3 (02) 145-154
20 Chittoor SR, Elsehety AE, Roberts GF, Laughlin WR. Sticky platelet syndrome: a case report and review of the literature. Clin Appl Thromb Hemost 1998; 4 (04) 280-284
21 Fodor M, Facskó A, Berényi E, Sziklai I, Berta A, Pfliegler G. Transient visual loss triggered by scuba diving in a patient with a petrous epidermoid and combined thrombotic risk factors. Pathophysiol Haemost Thromb 2007; 36 (06) 311-314
22 Kannan S. Recurrent arterial thrombosis in a young male: sticky platelet syndrome. Internet J Hematol 2008; 4 (01) 1-3
23 Sand M, Mann B, Bechara FG, Sand D. Sticky platelet syndrome type II presenting with arterial microemboli in the fingers. Thromb Res 2009; 124 (02) 244
24 Chaturvedi S, Dzieczkowski JS. Protein S deficiency, activated protein C resistance and sticky platelet syndrome in a young woman with bilateral strokes. Cerebrovasc Dis 1999; 9 (02) 127-130
25 Bick RL. Prothrombin G20210A mutation, antithrombin, heparin cofactor II, protein C, and protein S defects. Hematol Oncol Clin North Am 2003; 17 (01) 9-36
26 Lewerenz V, Burchardt T, Büchau A, Ruzicka T, Megahed M. Livedoid vasculopathy with heterozygous factor V Leiden mutation and sticky platelet syndrome [in German]. Hautarzt 2004; 55 (04) 379-381
27 Bick RL, Hoppensteadt D. Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update. Clin Appl Thromb Hemost 2005; 11 (01) 1-13
28 Ruiz-Argüelles GJ, López-Martínez B, Valdés-Tapia P, Gómez-Rangel JD, Reyes-Núñez V, Garcés-Eisele J. Primary thrombophilia in Mexico. V. A comprehensive prospective study indicates that most cases are multifactorial. Am J Hematol 2005; 78 (01) 21-26
29 Kahles H, Trobisch H, Kehren H. Disseminated coronary occlusions and massive pulmonary embolism in a 40-year-old woman [in German]. Dtsch Med Wochenschr 2006; 131 (13) 672-675
30 Randhawa S, Van Stavern GP. Sticky platelet syndrome and anterior ischaemic optic neuropathy. Clin Experiment Ophthalmol 2007; 35 (08) 779-781
31 Mühlfeld AS, Ketteler M, Schwamborn K. , et al. Sticky platelet syndrome: an underrecognized cause of graft dysfunction and thromboembolic complications in renal transplant recipients. Am J Transplant 2007; 7 (07) 1865-1868
32 El-Amm JM, Andersen J, Gruber SA. Sticky platelet syndrome: a manageable risk factor for posttransplant thromboembolic events. Am J Transplant 2008; 8 (02) 465
33 Mears KA, Van Stavern GP. Bilateral simultaneous anterior ischaemic optic neuropathy associated with Sticky Platelet Syndrome. Br J Ophthalmol 2009; 93 (07) 885-886 , 913
34 Bojalian MO, Akingba AG, Andersen JC. , et al. Sticky platelet syndrome: an unusual presentation of arterial ischemia. Ann Vasc Surg 2010; 24 (05) 691.e1-691.e6
35 Loeffelbein DJ, Baumann CM, Mücke T, Wolff KD, Hölzle F, Kesting MR. Sticky platelet syndrome as a possible cause for free flap failure--a case report. Microsurgery 2010; 30 (06) 466-468
36 Rac MW, Minns Crawford N, Worley KC. Extensive thrombosis and first-trimester pregnancy loss caused by sticky platelet syndrome. Obstet Gynecol 2011; 117 (2 Pt 2): 501-503
37 Gehoff A, Kluge JG, Gehoff P. , et al. Recurrent strokes under anticoagulation therapy: sticky platelet syndrome combined with a patent foramen ovale. J Cardiovasc Dis Res 2011; 2 (01) 68-70
38 Darulová S, Samoš M, Sokol J. , et al. Sticky platelets syndrome in a young patient with massive pulmonary embolism. Am J Case Rep 2013; 14: 169-172
39 Tekgündüz E, Demir M, Akyol Erikçi A, Akpınar S, Oztürk E, Kırkızlar O. Sticky platelet syndrome in patients with uninduced venous thrombosis. Turk J Haematol 2013; 30 (01) 48-52
40 Kubisz P, Stasko J, Holly P. Sticky platelet syndrome. Semin Thromb Hemost 2013; 39 (06) 674-683
41 Moncada B, Castillo-Martínez C, Ruiz-Argüelles GJ, Valdés-Tapia P, Arenas-Velázquez E. Sticky platelets syndrome: a frequent cause of primary thrombophilia. J Invest Dermatol 2013; 133 (Suppl. 01) S180
42 Yagmur E, Frank RD, Neulen J, Floege J, Mühlfeld AS. Platelet hyperaggregability is highly prevalent in patients with chronic kidney disease: an underestimated risk indicator of thromboembolic events. Clin Appl Thromb Hemost 2015; 21 (02) 132-138
43 Castillo-Martínez C, Moncada B, Valdés-Rodríguez R, González FJ. Livedoid vasculopathy (LV) associated with sticky platelets syndrome type 3 (SPS type 3) and enhanced activity of plasminogen activator inhibitor (PAI-1) anomalies. Int J Dermatol 2014; 53 (12) 1495-1497
44 Alsheekh AA, Puggioni A, Hingorani AP, Marks N, Ascher E. The sticky platelet syndrome during carotid endarterectomy. Ann Vasc Surg 2015; 29 (06) 1317.e9-1317.e11
45 Solis-Jimenez F, Hinojosa-Heredia H, García-Covarrubias L, Soto-Abraham V, Valdez-Ortiz R. Sticky platelet syndrome: an unrecognized cause of acute thrombosis and graft loss. Case Rep Nephrol 2018; 2018: 3174897
46 Ruiz-Delgado GJ, Cantero-Fortiz Y, Mendez-Huerta MA. , et al. Primary thrombophilia in Mexico XII: miscarriages are more frequent in people with sticky platelet syndrome. Turk J Haematol 2017; 34 (03) 239-243
47 Ruiz-Argüelles GJ, Alarcón-Urdaneta C, Calderón-García J, Ruiz-Delgado GJ. Primary thrombophilia in México VIII: description of five kindreds of familial sticky platelet syndrome phenotype. Rev Hematol Mex 2011; 12 (02) 73-78
48 Šimonová R, Bartosová L, Chudý P. , et al. Nine kindreds of familial sticky platelet syndrome phenotype. Clin Appl Thromb Hemost 2013; 19 (04) 395-401
49 Velázquez-Sánchez-de-Cima S, Zamora-Ortiz G, Hernández-Reyes J. , et al. Primary thrombophilia in México X: a prospective study of the treatment of the sticky platelet syndrome. Clin Appl Thromb Hemost 2015; 21 (01) 91-95
50 Staško J, Bartošová L, Mýtnik M, Kubisz P. Are the platelets activated in sticky platelet syndrome?. Thromb Res 2011; 128 (01) 96-97
51 Feng D, Lindpaintner K, Larson MG. , et al. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1999; 19 (04) 1142-1147
52 Cole VJ, Staton JM, Eikelboom JW. , et al. Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke. J Thromb Haemost 2003; 1 (05) 963-970
53 Ollikainen E, Mikkelsson J, Perola M, Penttilä A, Karhunen PJ. Platelet membrane collagen receptor glycoprotein VI polymorphism is associated with coronary thrombosis and fatal myocardial infarction in middle-aged men. Atherosclerosis 2004; 176 (01) 95-99
54 Muñoz X, Obach V, Hurtado B, de Frutos PG, Chamorro A, Sala N. Association of specific haplotypes of GAS6 gene with stroke. Thromb Haemost 2007; 98 (02) 406-412
55 Shaffer JR, Kammerer CM, Dorn J. , et al. Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians. Nutr Metab Cardiovasc Dis 2011; 21 (08) 546-552
56 Kubisz P, Ivankov J, Hollý P, Staško JN, Musiał J. The glycoprotein IIIa PL(A1/A2) polymorphism--a defect responsible for the sticky platelet syndrome?. Clin Appl Thromb Hemost 2006; 12 (01) 117-119
57 Kubisz P, Bartosová L, Ivanková J. , et al. Is Gas6 protein associated with sticky platelet syndrome?. Clin Appl Thromb Hemost 2010; 16 (06) 701-704
58 Ruiz-Argüelles GJ, Garcés-Eisele J, Camacho-Alarcón C. , et al. Primary thrombophilia in Mexico IX: the glycoprotein IIIa PLA1/A2 polymorphism is not associated with the sticky platelet syndrome phenotype. Clin Appl Thromb Hemost 2013; 19 (06) 689-692
59 Johnson AD, Yanek LR, Chen MH. , et al. Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. Nat Genet 2010; 42 (07) 608-613
60 Kubisz P, Ivanková J, Škereňová M, Staško J, Hollý P. The prevalence of the platelet glycoprotein VI polymorphisms in patients with sticky platelet syndrome and ischemic stroke. Hematology 2012; 17 (06) 355-362
61 Sokol J, Biringer K, Škereňová M. , et al. Platelet aggregation abnormalities in patients with fetal losses: the GP6 gene polymorphism. Fertil Steril 2012; 98 (05) 1170-1174
62 Kotuličová D, Chudý P, Škereňová M, Ivanková J, Dobrotová M, Kubisz P. Variability of GP6 gene in patients with sticky platelet syndrome and deep venous thrombosis and/or pulmonary embolism. Blood Coagul Fibrinolysis 2012; 23 (06) 543-547
63 Sokol J, Skerenova M, Biringer K, Lasabova Z, Stasko J, Kubisz P. Genetic variations of the GP6 regulatory region in patients with sticky platelet syndrome and miscarriage. Expert Rev Hematol 2015; 8 (06) 863-868
64 Škereňová M, Sokol J, Biringer K. , et al. GP6 haplotype of missense variants is associated with sticky platelet syndrome manifested by fetal loss. Clin Appl Thromb Hemost 2018; 24 (01) 63-69
65 Ferreiro JL, Gómez-Hospital JA, Angiolillo DJ. Platelet abnormalities in diabetes mellitus. Diab Vasc Dis Res 2010; 7 (04) 251-259
66 Vernstrøm L, Funck KL, Grove EL. , et al. Antiplatelet effect of aspirin during 24h in patients with type 2 diabetes without cardiovascular disease. Thromb Res 2018; 161: 1-6
67 Hu L, Chang L, Zhang Y. , et al. Platelets express activated P2Y₁₂ receptor in patients with diabetes mellitus. Circulation 2017; 136 (09) 817-833
68 Skowasch D, Tuleta I, Viktor A, Bauriedel G, Nickenig G. Diabetes mellitus is associated with increased ex vivo-platelet aggregation and decreased response to aspirin - antithrombotic potential of ACE-inhibitors and AT1-antagonists. Platelets 2009; 20 (05) 358-359
69 Zeck J, Schallheim J, Lew SQ, DePalma L. Whole blood platelet aggregation and release reaction testing in uremic patients. BioMed Res Int 2013; 2013: 486290
70 Harrison P, Mackie I, Mumford A. , et al; British Committee for Standards in Haematology. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155 (01) 30-44
71 Cattaneo M, Cerletti C, Harrison P. , et al. Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the Platelet Physiology Subcommittee of SSC/ISTH. J Thromb Haemost 2013; 11: 1183-1189
72 Burke N, Flood K, Murray A. , et al. Platelet reactivity changes significantly throughout all trimesters of pregnancy compared with the nonpregnant state: a prospective study. BJOG 2013; 120 (13) 1599-1604
73 D'Ascenzo F, Taha S, Moretti C. , et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol 2015; 115 (09) 1185-1193
74 Lamberts M, Olesen JB, Ruwald MH. , et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation 2012; 126 (10) 1185-1193