Arauna Diego, García Francisco, Rodríguez-Mañas Leocadio, Marrugat Jaume, Sáez Claudia, Alarcón Marcelo, Wehinger Sergio, Espinosa-Parrilla Yolanda, Palomo Iván, Fuentes Eduardo
Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, Universidad de Talca, Talca, Chile.
Department of Geriatric Medicine, Complejo Hospitalario de Toledo, Toledo, Spain.
Free Radic Biol Med. 2020 Mar;149:64-71. doi: 10.1016/j.freeradbiomed.2020.01.007. Epub 2020 Jan 8.
The elderly population is increasing worldwide and in Chile, it is expected to grow rapidly. The World Health Organization (WHO) ICOPE guideline (Integrated Care for Older People) emphasizes the importance of frailty diagnosis to prevent dependence. Frailty in older adults is considered an indicator of vulnerability and poor health outcomes, of multifactorial etiology. Our objective was to investigate the association of activation of coagulation and increased risk of thrombosis with frailty in people older than 64 years. A prevalent-case control study was designed with 28 frail older and 27 robust older adults (non-frail, control group) older than 64 years. Frailty was defined by Fried's Phenotype, Platelet aggregation and activation plasma levels of Thromboxane B2 (TXB2), 8-isoprostane and Growth Differentiation Factor-15 (GDF-15) were determined.
Compared to healthy controls, frail older adults, had a) higher percentage of platelet aggregation induction with ADP 4 μM (82.85% (3.35) and 73.41% (3.26), p-value = 0.024) and subaggregant dose of ADP (30.83% (7.47) and 13.25% (3.21), p-value = 0.002); b) higher platelet activation: P-selectin exposure (18.23% (4.41) and 6.96% (1.08), p-value = 0.011), and activated GPIIβ-IIIα (21.51% (3.41) and 8.26% (1.18), p-value = 0.001), at the baseline level and against a subaggregant dose ADP: P-selectin exposure (46.93% (5.95) and 13.41% (3.35), p-value = 0.002) and activated GPIIβ-IIIα (43.29% (6.04) and 26.71% (4.92), p-value = 0.024); c) higher plasma levels of TXB2 (201.8 ng/mL (59.53-236.3) and 45.77 ng/mL (25.14-98.26), p-value<0.0001), d) elevated plasma levels of 8-isoprostane (70.94 pg/mL, IQ: 65.89-99,96 and 56.24 pg/mL, IQ: 42.18-74.81, p-value = 0.001), and e) higher plasma GDF-15 levels (2,379 pg/mL, IQ: 1,845-4,121and 1367 pg/mL, IQ: 1190-1747, p-value = 0.0001).
Older adults with frailty syndrome have an upregulated platelet activity that may contribute to an increased risk of thrombosis and aspirin resistance. The elevated oxidative stress and increases of GDF-15 levels might be related to altered platelet responsiveness in frail patients.
The determination of biomarkers of platelet dysfunction, oxidative stress and cell senescence/mitochondrial dysfunction may contribute to frailty diagnosis, and approaches aimed at regulating platelet function in frail older adults could contribute to its prevention and treatment.
全球老年人口正在增加，智利预计老年人口将迅速增长。世界卫生组织（WHO）的ICOPE指南（老年人综合护理）强调了衰弱诊断对预防失能的重要性。老年人的衰弱被认为是易损性和不良健康结局的指标，其病因是多因素的。我们的目的是调查64岁以上人群中凝血激活与血栓形成风险增加和衰弱之间的关联。我们设计了一项现患病例对照研究，纳入了28名64岁以上的衰弱老年人和27名健壮老年人（非衰弱，对照组）。衰弱由弗里德表型定义，测定了血小板聚集以及血栓素B2（TXB2）、8-异前列腺素和生长分化因子-15（GDF-15）的血浆激活水平。
与健康对照组相比，衰弱老年人有：a）用4 μM ADP诱导血小板聚集的百分比更高（82.85%（3.35）和73.41%（3.26），p值 = 0.024）以及ADP亚聚集剂量时更高（30.83%（7.47）和13.25%（3.21），p值 = 0.002）；b）血小板激活更高：在基线水平以及针对ADP亚聚集剂量时，P-选择素暴露（18.23%（4.41）和6.96%（1.08），p值 = 0.011），以及活化的GPIIβ-IIIα（21.51%（3.41）和8.26%（1.18），p值 = 0.001）：P-选择素暴露（46.93%（5.95）和13.41%（3.35），p值 = 0.002）和活化的GPIIβ-IIIα（43.29%（6.04）和26.71%（4.92），p值 = 0.024）；c）TXB2的血浆水平更高（201.8 ng/mL（59.53 - 236.3）和45.77 ng/mL（25.14 - 98.26），p值<0.0001），d）8-异前列腺素的血浆水平升高（70.94 pg/mL，四分位数间距：65.89 - 99.96和56.24 pg/mL，四分位数间距：42.18 - 74.81，p值 = 0.001），以及e）血浆GDF-15水平更高（2379 pg/mL，四分位数间距：1845 - 4121和1367 pg/mL，四分位数间距：1190 - 1747，p值 = 0.0001）。
患有衰弱综合征的老年人血小板活性上调，这可能导致血栓形成风险增加和阿司匹林抵抗。氧化应激升高和GDF-15水平增加可能与衰弱患者血小板反应性改变有关。
血小板功能障碍、氧化应激和细胞衰老/线粒体功能障碍生物标志物的测定可能有助于衰弱诊断，旨在调节衰弱老年人血小板功能的方法可能有助于其预防和治疗。
