PROPHYLACTIC CALCIUM ADMINISTRATION IN PLATELETPHERESIS

由于离子钙（伊卡）水平降低，柠檬酸盐相关症状在血小板去除术期间很常见。预防性口服钙在预防这些症状中的作用尚未得到严格评价。我们进行了一项随机、安慰剂对照、双盲研究，探讨预防性口服钙剂在减轻血小板去除术中柠檬酸盐毒性症状方面的疗效。23名供体接受了4次90分钟的血小板单采术;每4 - 8周使用巴克斯特CS-3000装置以1.5 mg/kg/min的恒定柠檬酸盐输注速率进行一次。捐赠者在捐赠前30分钟随机接受1或2 g碳酸钙（1C或2C，以TUMS 500 mg/片提供）或外观相同的安慰剂（1 P或2 P）。症状评分为1（几乎不明显）、2（刺激性）、3（不舒服）或4（无法忍受）。对于大于或等于2级的症状，手术流速降低16%，对于4级症状，手术流速停止。在服用片剂之前和之后、献血期间每30分钟和献血后第二天分析血清样品。在献血前和献血后的现场样本和24小时采集中测量尿溶质。在完成所有四项程序之前，研究者均保持盲态。浓度单位为mmol/L，通过双尾McNemar和配对t检验进行统计。在90分钟时，与安慰剂相比，口服钙剂后的血清总钙（tCa）更高，2.24/2.13（2C/2 P，p小于0.000003）和2.20/2.13（1C/1 P，p小于0.0004），而2 gm后伊卡的绝对和百分比降低较低（2C/2 P：0.90/0.85和29/33%，p小于0.0006），但在1 gm口服钙后没有（1C/1 P：0.86/0.85和31/33%，p大于0.27）。与安慰剂相比，口服2 gm钙剂量的口周感觉异常显著改善（9例无变化，13例更好，2例供体更差，p <0.008），与安慰剂相比，两种剂量的钙后总体症状呈下降趋势（6/8 2级，4/6 3级和0/2 4级）（C/P）。所有组的血清柠檬酸盐水平相当。在所有组中，捐赠后与捐赠前相比，尿点钙排泄显著增加（超过7倍）。实验室数据显示，在未口服钙的献血者中，存在持续的钙依赖状态的趋势：服用安慰剂（1 P至2 P）后，第二天甲状旁腺激素（PTH）增加（17%至34%），尿钙排泄量减少（4%至7%），而口服钙剂（1C-2C）后，第二天PTH减少（5%至13%），钙排泄量增加（13%至23%）。这些数据表明，在血小板去除术前30分钟摄入市售口服碳酸钙制剂可减少供体症状并增加血清Ca水平。2 gm与1 gm剂量的效果更明显，表明更高剂量可能显示出更大的疗效。PTH反应和钙排泄在24小时内的变化表明，应开始对频繁血小板捐献者的骨代谢和钙平衡进行进一步研究。

Citrate-related symptoms, due to decreased ionized calcium (iCa) levels, are common during plateletpheresis. The role of prophylactic oral calcium administration in preventing such symptoms has not been critically evaluated. We performed a randomized, placebo-controlled, double-blind study of the efficacy of prophylactic oral calcium administration in mitigating symptoms of citrate toxicity during plateletpheresis. Twenty-three donors underwent four 90-minute platelet-pheresis procedures each; performed every 4 to 8 weeks at constant citrate infusion rates of 1.5 mg/kg/min, using a Baxter CS-3000 device. Donors randomly received either calcium carbonate 1 or 2 gm (1C or 2C, supplied as TUMS 500 mg/tablet) or an identical-appearing placebo (1P or 2P) 30 minutes before donation. Symptoms were scored as 1 (barely noticeable), 2 (irritating), 3 (uncomfortable), or 4 (unbearable). Procedure flow rates were decreased by 16 percent for symptoms greater than or equal to grade 2 and stopped for grade 4 symptoms. Serum samples were analyzed before and after tablet ingestion, every 30 minutes during donation, and the day after donation. Urinary solutes were measured in both spot samples and 24-hour collections pre- and post-donation. Investigators were blinded until completion of all four procedures. Concentrations are in mmol/L, statistics are by 2-tailed McNemar and paired t-tests. At 90 minutes, serum total calcium (tCa) was higher after either oral calcium dose compared to placebo, 2.24/2.13 (2C/2P, p less than 0.000003) and 2.20/2.13 (1C/1P, p less than 0.0004), while the absolute and percent decrease in iCa was lower after 2 gm (2C/2P: 0.90/0.85 and 29/33 percent, p less than 0.0006) but not after 1 gm (1C/1P: 0.86/0.85 and 31/33 percent, p greater than 0.27) of oral calcium. Circumoral paresthesias improved significantly with the 2 gm oral calcium dose compared to placebo (unchanged in nine, better in 13, worse in two donors, p less than 0.008), with a trend toward decreased overall symptoms (6/8 grade 2, 4/6 grade 3, and 0/2 grade 4) after either dose of calcium compared to placebo (C/P). Serum citrate levels were equivalent in all groups. Post- versus pre-donation urinary spot calcium excretion increased markedly (greater than seven-fold) in all groups. Laboratory data revealed a trend toward a sustained calcium-avid state in donations without oral calcium: day-after parathyroid hormone (PTH) increased (17 to 34 percent) and urinary calcium excretion decreased (4 to 7 percent) after placebo (1P to 2P), while day-after PTH decreased (5 to 13 percent) and calcium excretion increased (13 to 23 percent) after oral calcium (1C-2C). These data show that ingestion of a commercially available preparation of oral calcium carbonate 30 minutes prior to plateletpheresis reduces donor symptoms and increases serum Ca levels. The more pronounced effect of the 2 gm versus 1 gm dose suggests that higher doses might show even greater efficacy. The changes in PTH response and calcium excretion over 24 hours suggest that future studies of bone metabolism and calcium balance in frequent platelet donors should be initiated.