“Sticky Platelet Syndrome”: In Vitro Response to Small Dose Aspirin Is Reflected in Clinical Benefit.

Introduction: “Sticky Platelet Syndrome” (SPS), a consistently demonstrable platelet aggregability to subthreshold concentrations of epinephrine and/or adenosine dinucleotide phosphate (ADP), is an autosomal dominant condition with thrombotic consequences (Mammen, 1984). Because published studies regarding SPS are few and platelet function testing unusual in thrombophilia evaluation, SPS may be an under-recognized contributor to arterial and venous thrombosis. The precise pathogenesis of SPS is undefined, but prior observations have suggested that small-dose aspirin may be useful in modulating increased aggregability and preventing recurrent thrombosis.

Methods: Laboratory and clinical response to aspirin in patients with SPS was determined by retrospective review of a large university thrombophilia clinic database in which platelet function was a routine component of extensive thrombophilia testing. As previously reported, SPS was diagnosed by demonstration of aggregation amplitude of 50% or more with epinephrine and/or ADP concentrations 20-fold lower than routine activation thresholds on two separate occasions at least 2 weeks apart. Records of individuals exhibiting SPS prescribed antiplatelet therapy for whom follow-up laboratory and clinical data were available were analyzed for modulation of aggregation abnormality and clinical outcome. Laboratory response to anti-platelet therapy was defined as return of function to laboratory “normal” or “decreased” function on testing >2 weeks following initiation of therapy. Platelet function and clinical outcomes were followed for 6 months to 13 years.

Results: Of 149 patients with treated SPS, 97 (65%) had one or more thrombotic events prior to presentation 42/149 (28%) despite warfarin or low molecular weight heparin therapy. Of 149, 53% had venous, 35% arterial, 5% both arterial and venous events; 7% had recurrent fetal loss. 52/149 (35%) were individuals evaluated for primary family relationship to an SPS patient. 25 (16.7%) patients had SPS as a solitary risk factor. 147/149 patients (98.6%) demonstrated reversal of hyperfunction, 108/147 (73%) with aspirin (81mg/day); all responders normalized with </= 325 mg aspirin daily and experienced no significant side-effects. Aspirin was used in 56% of patients as a sole anti-thrombotic agent, in 27% with anticoagulants (warfarin or a parenteral agent), in 10% with other anti-platelet agent(s), in 2% with anticoagulant and anti-platelet agent(s). 4% of patients received no aspirin because of allergy. Of those demonstrating response, 7 patients (4.8%) had a further thrombotic event. Of these, 2 patients received clopidogrel alone due to aspirin allergy and 5 patients received aspirin plus anticoagulants at “therapeutic” levels; all had multiple thrombotic risk factors.

Conclusions: Aspirin, in minimal, inexpensive, well-tolerated doses, “normalized” in vitro platelet function in SPS patients and prevented thrombosis recurrence in most, many of whom had experienced rethrombosis on anticoagulants alone. Because undiagnosed platelet hyperfunction (identified in 1/3 of patients evaluated at a large urban university center: Faraz et al., 2007) may predispose to rethrombosis and classical anticoagulants alone do not abrogate thrombogenic potential in pateints with SPS, platelet function testing deserves a place in thrombophilia evaluation - and may be of greater utility than the currently performed “thrombophilia panels.”