PROPHYLACTIC CALCIUM ADMINISTRATION IN PLATELETPHERESIS

由于电离钙(ICA)水平降低，与柠檬酸盐相关的症状在血小板移植过程中很常见。预防性口服钙剂在预防此类症状中的作用尚未得到严格的评价。我们进行了一项随机、安慰剂对照、双盲研究，研究预防性口服钙剂在减轻血小板移植期间柠檬酸盐中毒症状方面的效果。23名捐献者每人接受了4次90分钟的血小板采集程序；使用Baxter CS-3000设备，以1.5 mg/kg/min的恒定柠檬酸盐输注速度每4至8周进行一次。捐献者在捐献前30分钟随机接受1或2克碳酸钙(1C或2C，以TUMS 500 mg/片的形式供应)或外观相同的安慰剂(1P或2P)。症状分为1分(几乎不明显)、2分(烦人)、3分(不舒服)或4分(无法忍受)。对于大于或等于2级的症状，流程流率降低了16%，对于4级的症状，流程停止。在服药前、服药后、捐献过程中每隔30分钟、捐献后第二天对血清样本进行分析。在捐献前和捐献后24小时采集尿液样本，并测定尿液溶质。调查人员被蒙在鼓里，直到完成所有四个程序。浓度以摩尔比/L为单位，统计采用双尾麦克内玛和配对t检验。口服钙剂90min后，血清总钙明显高于安慰剂，分别为2.24/2.13(2C/2P，P<0.000003)和2.20/2.13(1C/1P，P<0.0004)，而ICA绝对值和百分比在2克后下降较小(2C/2P：0.90/0.85和29/33%，P<0.0006)，但在1克后不再下降(1C/1P：0.86/0.85和31/33%，P<0.0006)。P>0.27)。与安慰剂(C/P)相比，服用2克口服钙剂后，口腔周围感觉异常明显改善(9人没有变化，13人好转，2人更差，p<0.008)，与安慰剂(C/P)相比，两种剂量的钙剂都有减轻总体症状(6/8级2级，4/6级3级和0/2级4级)的趋势。所有组的血清柠檬酸水平相同。与捐献前相比，所有组的尿钙排泄量均显着增加(超过7倍)。实验室数据显示，没有口服钙的捐赠者有持续贪钙的趋势：服用安慰剂(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%)，而服用口服钙(1C-2C)后，甲状旁腺激素(PTH)下降(5%至13%)，钙排泄增加(13%至23%)。这些数据表明，在血小板移植前30分钟摄入一种市售的口服碳酸钙制剂可以减轻供者的症状，并增加血清钙水平。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好的疗效。甲状旁腺素反应和钙排泄在24小时内的变化表明，未来应该开始对频繁的血小板捐献者进行骨代谢和钙平衡的研究。

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.