Division of Biostatistics and Epidemiology, RTI International, Durham, NC, United States of America.
Vitalant Research Institute, Denver, CO, United States of America.
Blood Transfus. 2019 Jul;17(4):263-273. doi: 10.2450/2019.0053-19.
Sex hormone intake in blood donors may affect the quality of red blood cell (RBC) products via modulation of RBC function and predisposition to haemolysis during cold storage. The aims of this study were to evaluate the association between female sex hormone intake and RBC storage outcomes, and to examine possible mechanisms by which sex hormones interact with RBCs.
Sex hormone intake by race/ethnicity and menopausal status, and association analyses between hormone intake and donor scores of storage, osmotic or oxidative haemolysis, were evaluated in 6,636 female donors who participated in the National Heart, Lung and Blood Institute's RBC-Omics study. A calcium fluorophore, Fluo-3AM, was used to define RBC calcium influx in response to exogenous sex hormones or transient receptor potential cation (TRPC) channel drugs.
Sex hormone intake was more prevalent in premenopausal women from all racial groups (18-31%) than in postmenopausal women (4-8%). Hormone intake was significantly (p<0.0001) associated with reduced storage haemolysis in all females, reduced osmotic haemolysis in postmenopausal donors (23.1±10.2% vs 26.8±12.0% in controls, p<0.001), and enhanced susceptibility to oxidative haemolysis in premenopausal women. In vitro, supraphysiological levels of progesterone (10 μmol/L), but not 17β-oestradiol or testosterone, inhibited calcium influx into RBC and was associated with lower spontaneous haemolysis after 30 days of cold storage (0.95±0.18% vs 1.85±0.35% in controls, p<0.0001) or in response to a TRPC6 activator.
Sex hormone intake in female donors is associated with changes in RBC predisposition to haemolysis. Menstrual status and the type of hormone preparation may contribute to differences in haemolytic responses of female RBCs to osmotic and oxidative stress. Progesterone modulates calcium influx into RBC via a mechanism that may involve interactions with membrane TRPC6 channels.
献血者血液中的性激素摄入可能通过调节 RBC 功能和在冷藏过程中增加溶血倾向来影响 RBC 产品的质量。本研究的目的是评估女性性激素摄入与 RBC 储存结果之间的关联，并探讨性激素与 RBC 相互作用的可能机制。
在参加国家心肺血液研究所 RBC-Omics 研究的 6636 名女性献血者中，按种族/民族和绝经状态评估了性激素摄入情况，以及激素摄入与献血者储存评分、渗透或氧化溶血之间的关联分析。使用钙荧光探针 Fluo-3AM 来定义外源性性激素或瞬时受体电位阳离子 (TRPC) 通道药物引起的 RBC 钙内流。
所有种族的绝经前女性（18-31%）比绝经后女性（4-8%）更普遍摄入性激素。激素摄入与所有女性的储存溶血减少显著相关（p<0.0001），绝经后献血者的渗透溶血减少（23.1±10.2%比对照组的 26.8±12.0%，p<0.001），以及绝经前女性对氧化溶血的易感性增强。在体外，生理浓度以上的孕激素（10 μmol/L），而不是 17β-雌二醇或睾酮，抑制 RBC 钙内流，并与冷藏 30 天后自发溶血减少相关（0.95±0.18%比对照组的 1.85±0.35%，p<0.0001）或对 TRPC6 激活剂的反应。
女性献血者的性激素摄入与 RBC 溶血倾向的变化有关。月经状态和激素制剂类型可能导致女性 RBC 对渗透和氧化应激的溶血反应存在差异。孕激素通过一种可能涉及与膜 TRPC6 通道相互作用的机制调节 RBC 钙内流。
