Aggregometry detects platelet hyperreactivity in healthy individuals

Abstract

Aggregometry is widely used to assess platelet function, but its use in identifying platelet hyperreactivity is poorly defined. We studied platelet aggregation in 359 healthy individuals using the agonists adenosine diphosphate (ADP), epinephrine, collagen, collagen-related peptide, and ristocetin. We also assessed the reproducibility of these assays in 27 subjects by studying them repeatedly on at least 4 separate occasions. Healthy subjects exhibited considerable interindividual variability in aggregation response to agonists, especially at concentrations lower than those typically used in clinical laboratories. For each agonist tested at these submaximal concentrations, a small proportion of individuals demonstrated an unusually robust aggregation response. Subjects who exhibited such in vitro hyperreactivity to one agonist tended to demonstrate a similar response to others, suggesting that hyperreactivity is a global characteristic of platelets. Epinephrine and collagen-related peptide were especially reliable and efficient in detecting hyperreactivity. For epinephrine, excellent reproducibility persisted for up to 3 years, and hyperreactivity was associated with female sex and higher fibrinogen levels (P < .02). We recommend these assays as appropriate candidates for future studies requiring accurate assessment of increased platelet reactivity. These include clinical studies to improve risk assessment for arterial thrombosis, as well as genetic studies to establish determinants of the hyperreactive platelet phenotype. (Blood. 2005;106:2723-2729)

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“…Using lower concentrations of ADP allows us to detect platelet hyperreactivity, which was defined as ≥30% aggregation induced by 2.5 μM ADP. In a previous study of 359 healthy subjects, ADP at 1.5-2.5 μM was used to differentiate hypo-from hyperreactive platelets (19). This concentration of ADP does not induce significant platelet aggregation in most healthy subjects.…”

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“…4 Thus, a variety of candidate gene and genomewide association studies are under way to identify the source of platelet hyperactivity. 5 Further, platelets from certain patients exhibit diminished reactivity to drug or therapy.…”

“…[2][3] The DIC theory is supported by the presence in APL of elevated levels of tissue factor and cancer procoagulant. 4 In favor of the fibrinolytic mechanism is the presence of elevated levels of annexin II (ANXII) detected on APL leukemic cells 5 and of normal …”

Blood Platelets and Systemic Sclerosis

“…Platelet r e s p o n s e t o a g o n i s t s a s m e a s u r e d b y t h e hyperactive phenotype is often difficult to interpret. There is a significant variability between individuals, as several genetic modifiers may influence platelet function and as platelet hyperactivity, as measured by aggregometry, can be detected in healthy individuals [147,148]. Also, in vivo, platelet activation results from the combinational input of agonists that act in a complex synergistic way and vary from donor to donor [149][150][151][152].…”