First Report of Elevated Monocyte-Platelet Aggregates in Healthy Children

Abstract

Platelets are subcellular fragments which circulate in blood and have well established roles in thrombosis and haemostasis in adults. Upon activation, platelets undergo granule exocytosis and express P-Selectin on the cell membrane which binds a ligand on monocytes, leading to monocyte-platelet aggregation. Elevated circulating monocyte-platelet aggregates in adults are linked to atherothrombosis, but have not been investigated in children where thrombosis is less common. This study aimed to measure monocyte-platelet aggregate formation in children using whole blood flow cytometry. Monocyte-platelet aggregates as well as activation and granule exocytosis of platelets were measured in healthy adults (n = 15, median age 28 years) and healthy children (n = 28, median age 7 years). Monocyte-platelet aggregates in healthy children were elevated compared to healthy adults (37.8±4.4% vs 15.5±1.9% respectively, p<0.01). However, this was not accompanied by any difference in platelet activation (PAC-1 binding 6.8±1.5% vs 6.3±2.0% respectively, p = ns) or granule exocytosis (P-selectin expression 4.4±0.5% vs 3.1±0.5% respectively, p = ns). Despite comparable numbers of platelets bound per monocyte (GPIb MFI 117.3±13.7 vs 130.9±28.6 respectively, p = ns), surface P-selectin expression per platelet-bound monocyte was lower in children compared to adults. We therefore provide the first data of elevated monocyte-platelet aggregates in healthy children.

Platelets from children are hyper‐responsive to activation by thrombin receptor activator peptide and adenosine diphosphate compared to platelets from adults

“…While platelet activation markers as measured by flow cytometry are not used in routine clinical practice, it provides important molecular information about the mechanism of platelet interactions (Michelson et al, 2007). Our previous study (Yip et al, 2013), together with this current study highlights the need to establish age-specific reference ranges for agonist-stimulated platelet activation for interpreting platelet reactivity in children.…”

“…We recently reported that circulating MPA are elevated in healthy children compared to adults (Yip et al, 2013). To date, there is limited data of in vitro platelet response to various agonists at sub-maximal concentrations in healthy children.…”

Challenges and Priorities for Research

“…Recent studies confirming different baseline biology of platelets in children compared with adults confirm the need for specific study of all these agents in children. 64 …”

“…Not approved (pediatric use reported): no pediatric-specific trials ongoing, at least one pediatric case report published. Not approved (no pediatric use reported): no pediatric-specific trials ongoing, no case report published by guest on May 11, 2018 http://circ.ahajournals.org/ Downloaded from studies, the use of novel end points such as net clinical benefit, and the use of novel trial designs, including n of 1 trials and response-adaptive randomization.…”

“…by guest on May 11, 2018 http://circ.ahajournals.org/ Downloaded from a single perspective (for example, hematology, cardiology or cardiovascular surgery, imaging) rather than having a multidimensional and interdisciplinary outlook. This challenge, along with the limited number of patients available at individual institutions, will require widespread collaboration among clinicians, research groups, experts, institutions, and stakeholders to achieve important advances in this field.…”