PROPHYLACTIC CALCIUM ADMINISTRATION IN PLATELETPHERESIS

柠檬酸盐相关症状，由于降低离子钙（iCa）水平，是常见的血小板采集。预防性口服钙在预防此类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，研究预防性口服钙在血小板采集期间减轻柠檬酸盐毒性症状的疗效。23名献血者每人接受了4次90分钟的血小板采集；使用百特CS-3000装置，以1.5 mg/kg/min的恒定柠檬酸滴注速率每4至8周进行一次。献血者在捐献前30分钟随机接受碳酸钙1或2克（1C或2C，以TUMS 500毫克/片的形式提供）或外观相同的安慰剂（1P或2P）。症状分为1（几乎不明显）、2（刺激）、3（不舒服）或4（无法忍受）。对于大于或等于2级的症状，手术流程率降低16%，对于4级症状，手术流程率停止。分别在服药前后、捐献期间每隔30分钟及捐献后第一天对血清样本进行分析。在捐赠前后的现场样品和24小时收集中测量尿溶质。研究者在完成所有四个程序之前都是盲法的。浓度单位为mmol/L，统计数据采用双尾McNemar检验和配对t检验。90分钟时，口服钙剂量组血清总钙（tCa）高于安慰剂组，分别为2.24/2.13 （2C/2P, p < 0.000003）和2.20/2.13 (1C/1P, p < 0.0004)，而口服钙剂量组2 gm （2C/2P: 0.90/0.85和29/ 33%，p < 0.0006）后，iCa的绝对降低率和百分比较低，但口服钙剂量组1 gm （1C/1P: 0.86/0.85和31/ 33%，p > 0.27）后，iCa的绝对降低率和百分比较低。与安慰剂相比，口服2 gm钙剂量显著改善了环口感觉异常（9例不变，13例好转，2例恶化，p < 0.008），两种剂量的钙与安慰剂相比，总体症状（6/8级2、4/6级3和0/2级4）都有下降的趋势（C/ p）。各组血清柠檬酸水平相同。与捐献前相比，捐献后尿点钙排泄量明显增加（超过7倍）。实验室数据显示，在没有口服钙的捐赠中，有持续钙渴求状态的趋势：安慰剂（1P至2P）后，甲状旁腺激素（PTH）增加（17%至34%），尿钙排泄减少（4%至7%），而口服钙（1C-2C）后，甲状旁腺激素（PTH）减少（5%至13%），钙排泄增加（13%至23%）。这些数据表明，在采血小板前30分钟服用市售的口服碳酸钙制剂可减轻供体症状并提高血清钙水平。2克剂量比1克剂量的效果更明显，这表明更高的剂量可能会显示出更大的效果。PTH反应和钙排泄在24小时内的变化表明，应该开始对频繁血小板供体的骨代谢和钙平衡进行进一步的研究。

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.