Increase in density and accumulation of serotonin by human aging platelets

Abstract

51Cr-labeled autologous platelets were infused into splenectomized subjects and the specific radioactivities of high-density (HD) and low-density (LD) platelet subpopulations were determined sequentially in postinfusion samples. A rapid decrease in the specific radioactivity of LD cohorts (T1/2 = 2.5 days) was observed, but the specific radioactivity of HD platelets remained constant or increased slightly during the first 4 days and then gradually declined for the next 5 days. No experimental artifacts during the platelet-labeling steps that could account for these results were demonstrated. These findings confirm previous observations in eusplenic individuals and support the hypothesis that human LD platelets are, on the average, younger than HD platelets. LD platelets contain 33.8 +/- 13.5 ng serotonin (5HT)/10(8) platelets and HD platelets 76.8 +/- 9.5 ng 5HT/10(8) platelets (P less than 0.001). Sequential measurements of 5HT in PRP platelets were performed during the recovery phase of thrombocytopenia following splenectomy in patients with idiopathic thrombocytopenic purpura (ITP), a condition associated with aging of platelets in circulation. Presplenectomy platelet 5HT was 17.7 ng/10(8) platelets and on days 1, 6, and 12 after surgery it increased to 18.1, 37.8, and 61.0 ng/10(8) platelets (n = 7). When three healthy volunteers were given aspirin (500 mg/day) for up to 15 days, no significant change in the 5HT content of circulating platelets was observed. If aspirin blocks, at least partially, the secretory process in vivo without interfering the 5HT uptake by the platelets, this finding stands against the possibility that a net depletion of 5HT occurs during the life-span of normal human platelets. The observation that human HD platelets, enriched with older cells, contain more 5HT than LD platelets taken together with the parallel increase in platelet 5HT and age during the recovery from thrombocytopenia in ITP patients and the lack of effect of aspirin on platelet 5HT content, provides initial evidence that human platelets accumulate 5HT during their life-span in circulation.

Advances in Platelet Subpopulation Research

“…This view was more in line with that of Paulus that thrombopoiesis is likely responsible for platelet heterogeneity and not aging in circulation, but that only a single platelet population exists and the only size heterogeneity is that inherent to the log normally distributed population (25). Consistent with this thesis, other studies demonstrated that in the steady state platelet density does not change with circulatory age (26, 27), while others still showed that platelet density may increase with time due to accumulation of 5-hydroxytryptamine (5-HT) (28).…”

Origin of the blood hyperserotonemia of autism

“…Since the platelet uptake rate depends on the 5-HT concentration in the surrounding plasma, generally, u i ( t 1 ) ≠ u i ( t 2 ). However, the 5-HT uptake and distribution of platelets appear to be little affected by their age or by how much 5-HT they have already accumulated [ 14 , 27 ]. Also, the numbers of platelets in blood vessels are very large and can be considered constant.…”

Inhibition of angiogenesis by platelets in systemic sclerosis patients

“…We observed that intraplatelet serotonin was decreased in patients with diffuse SSc compared with patients with limited SSc and healthy control subjects. Given that the serotonin content of platelets increases as platelets age in the circulation, this finding may be explained by a decreased platelet lifespan in the circulation with a consequent increased turnover in diffuse SSc [ 43 ]. However, this is also compatible with the notion of damaged endothelium-mediated platelet activation and accelerated removal of platelets from the circulation.…”