A new decade awaits sticky platelet syndrome: where are we now, how do we manage and what are the complications?

ABSTRACT

Introduction

Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial.

Areas covered

The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: ‘sticky platelet syndrome’ – ‘platelet hyperreactivity’ – ‘platelet hyperaggregability’). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems.

Expert Opinion

Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.

PLAIN LANGUAGE SUMMARY

Sticky platelet syndrome is aplatelet function disorder. It is associated with an increased risk of venous thromboembolism, arterial thrombosis, and obstetric placenta-mediated complications. Increased aggregation after low-dose ADP and/or epinephrine is the defining laboratory feature. Furthermore, afew studies report the familiar occurrence with possible genetic background. Several issues regarding the syndrome remain controversial: its exact etiology, genetics, optimal diagnostic, and treatment approach. These uncertainties provide ground for debate of the syndrome as aunique clinical entity. The review has two goals. Firstly, it summarizes the published studies and the actual definition of the syndrome. Secondly, it tries to point out the open pathophysiologic, diagnostic, and therapeutic problems.

KEYWORDS:

• Light transmission aggregometry
• platelet function disorder
• platelet hyperaggregability
• placenta-mediated complications
• thromboembolism
• thrombophilia

Article Highlights

• sticky platelet syndrome is a thrombophilic platelet function disorder with a familiar occurrence and autosomal trait, defined by the increased aggregation after low-dose ADP and/or epinephrine

• the prominent clinical features include various thromboembolic events, including arterial and atypical thrombosis, obstetric placenta-mediated complications, the ineffectiveness of standard anticoagulant therapy in secondary thromboprophylaxis, and good efficacy of antiplatelet agent acetylsalicylic acid

• with large-scale studies lacking, case reports, case series, and only a few retrospective studies provide clinical evidence on etiology, diagnostics, and treatment

• the etiology remains unresolved; the interaction of multiple genes and environmental factors is likely involved

• the unsatisfactory standardization of platelet aggregometry resulting in reproducibility issues represents a crucial problem for diagnostics

• solid evidence on the efficacy and safety of acetylsalicylic acid has been accumulated, whereas the data on other antiplatelet agents are scarce

List of Abbreviations

ADP, adenosine diphosphate; APCR, resistance to activated protein PC; APS, antiphospholipid syndrome; ASA, acetylsalicylic acid; AT, arterial thrombosis; ATb, antithrombin; CAD, coronary artery disease; CKD, chronic kidney disease; COXi, cyclo-oxygenase inhibitors; DM, diabetes mellitus; EPI, epinephrine; GP, glycoproteins; HHC, hyperhomocysteinemia; IVF, in vitro fertilization; LMWH, low molecular weight heparin; LTA, light transmittance aggregometry; miRs, MicroRNAs; MPN, myeloproliferative neoplasms; NSAID, non-steroid anti-inflammatory drugs; PC, protein C; PS, protein S; ref., references; SLE, systemic lupus erythematosus; SNPs, single nucleotide polymorphisms; SNVs, single nucleotide variations; SPS, Sticky platelet syndrome; TIA, transient ischemic attack; TRAP-6, thrombin receptor-activating peptide 6; UD, unpublished data; VKA, vitamin K antagonists; VTE, venous thromboembolism; vWF, von Willebrand factor

Reviewers disclosure statement

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was funded by Jessenius Faculty of Medicine in Martin of the Comenius University in Bratislava, Slovakia, and University Hospital in Martin, Slovakia. In addition, it was funded by projects of the Agency for the Support of Research and Development (APVV) APVV 16-0020 and Scientific Grant Agency (Vega) Vega 1/0479/21.