The condition known as sticky platelet syndrome (SPS) was first described in 1983; however, its prevalence did not receive substantial recognition in medical literature until much later (1-25). SPS is a relatively common cause of thrombosis (20,26-31), and is associated with both unexplained arterial and venous thrombotic events (32-34). Three forms of the SPS have been identified: Types I, II and III are defined by platelet hyperaggregability with both epinephrine and adenosine-diphosphate (ADP), type II with only epinephrine and type III with only ADP (13,31,35-39). The platelet abnormality appears to be congenital, based on familial occurrence, but the precise nature of the defect has not been defined. Treatment of SPS relies on diminishing the inherent platelet hyperaggregability by means of anti-platelet drugs; in most cases, aspirin appears adequate but there are situations in which other anti-platelet drugs must be employed (27,33,36,40-43) (see Table 1). Only one paper has described a prospective study of SPS treatment (40), and it proved that by using antiplatelet drugs, mainly aspirin, the platelet hyperreactivity of patients can be reverted and that this translates into a low re-thrombosis rate (36,40). Herein, we analyze the salient features of treatment of persons with SPS who have been identified in different parts of the world.
We employed the PubMed database to search for all entries with the term “Sticky Platelet”, either in the title and/or the abstract. The relevant features of all publications were further analyzed, focusing in the treatment features and the re-thrombosis rate.
The initial search identified 108 papers in total. However, although 41 of these included the search terms, they were discarded as they did not actually describe SPS. Twenty-four papers comprised reviews on SPS and 43 papers described either cases or series of patients. These latter 43 papers (Table 1) were further assessed. The country with the greatest number of papers published on SPS was the United States (fourteen publications), followed by Slovakia (eleven publications), Germany (eight publications), and México (six publications), with Hungary, Turkey, Russia and New Zealand having only a single publication each (23,26,52,53) (see Figure 1). In these publications, a total of 1783 patients with SPS were identified over the past 30 years [1988–2019] (see Figure 2). The thromboses identified were both venous or arterial; in some patients, SPS was identified together with another thrombophilic condition, either acquired or inherited (10,25,39) (see Table 1). Three hundred thirty two patients were treated with antiplatelet drugs; 303 were given solely aspirin and 29 received combinations with aspirin (heparin or coumadin), whereas two persons did not receive aspirin (heparin + alteplase; abciximab) (see Figures 3 and 4).
The doses of aspirin employed ranged between 80 and 325 mg/day (see Table 1); information about the use of enteric-coated versus non-coated aspirin is unavailable. The re-thrombosis rate for patients given antiplatelet drugs was 5/325 (1.5%); two of these patients were given subsequently direct oral anticoagulants. In only two papers were platelet aggregometry studies repeated after the treatment, as a way to control the efficacy of the treatment (4,40).
Over past years, we have been interested in analyzing the changes in the hemostatic system of Mexican Mestizos which can result in thrombophilia (40,42). In our studies, SPS was found to be the second most frequent thrombophilic condition identified in Mexican mestizos who expressed any clinical marker of thrombophilia (42), only exceeded by the MTHFR gene 677 C->T mutation. In México, we (11,19,24,42) and others (64) have found that approximately 50% of Mexican mestizo patients with a clinical maker of thrombophilia display the SPS phenotype. Most patients with SPS display other thrombosis-prone conditions, but there are also instances which SPS is identified as the single thrombophilia marker. Thus, SPS likely contributes to so-called “multifactorial thrombophilia” (19).
There are limited papers dealing with SPS treatment (Table 1); and most experiences stem from small series of patients or reviews (6,10,12,15,20,24,32,37,39,42,47-49,51,53,55,57-62,65-67) or case reports (4,8,17,21,23,25-30,34,44-46,50,52,54,56,63,68). Persons with the SPS phenotype but no history of thrombosis may not need treatment at all, but it is not irrational to prescribe them low doses of aspirin. For patients with history of thrombosis and the SPS phenotype, in a prospective study (40), we found that the platelet hyperaggregability can be reverted by means of aspirin in most cases (75%), whereas other/additional antiplatelet drugs were needed in the remaining 25% (with clopidogrel employed in our experience). Use of antiplatelet drugs enabled a low re-thrombosis rate at 129 months of 3.6%, thereby permitting freedom from re-thrombosis of 96.4% of the whole group of 55 patients at 129 months (40). The re-thrombosis rate that we found in our previous prospective study (3.6%), contrasts with that observed in the whole group of patients which we are presenting here (1.5%); this may stem from the fact that the data collection period in our group is substantially longer. In our prospective study (40), we analyzed the platelet hyperreactivity before and after the delivery of the antiplatelet drug and switched from aspirin to clopidogrel if the laboratory abnormally did not revert with aspirin (i.e., ‘aspirin resistance’ or ‘high on treatment aspirin activity’) (40). In another papers, we have suggested that pregnant women with the SPS phenotype should be given aspirin during all the pregnancy, mainly if they have experienced previous miscarriages (32,69,70). In the studies which we have now analyzed, only two (4,40) refer to repeating the platelet aggregation studies after starting antiplatelet drug therapy and then switching to another drug based on such testing; interestingly, despite the lack of any laboratory control of the treatment of persons with SPS, the re-thrombosis rate was very low (1.5%). This finding could militate against the recommendation of controlling the SPS treatment by means of platelet aggregometry studies but needs further investigation. There is no information available on the re-thrombosis rate in SPS patients not given antiplatelet drugs. Figure 5 refers to the algorithm that we suggest to treat patients with SPS, based on our experience and that stemming from the papers herein analyzed (19).
In summary, we have found that physicians worldwide are aware of the fact that the best treatment for persons with the SPS is the use of antiplatelet drugs. The rethrombosis rate is very low. Additional research on the SPS may be needed to better understand the pathophysiology of the condition; in the meanwhile, offering antiplatelet drugs to persons displaying the SPS phenotype seems adequate.
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Cite this article as: García-Navarrete YI, Vallejo-Villalobos MF, Olivares-Gazca JM, Cantero-Fortiz Y, León-Peña AA, Olivares-Gazca JC, Murrieta-Álvarez I, Ruiz-Delgado GJ, Ruiz-Argüelles GJ. Primary thrombophilia XV: antithrombotic treatment of sticky platelet syndrome worldwide. Ann Blood 2019;4:15.