翻譯：任文鑫  編輯：馮玉蓉  審校：曹瑩

背景：肝素誘導(dǎo)的血小板減少癥(HIT)會(huì)使心臟手術(shù)患者面臨致命并發(fā)癥的高風(fēng)險(xiǎn)。如果存在抗PF4/肝素抗體(抗PF4/Hep Ab)，有兩種方案可防止搭橋術(shù)中的血小板聚集：第一，使用替代抗凝劑，第二，肝素和抗聚集劑聯(lián)合使用。新型P2Y₁₂抑制劑——Cangrelor，可能是后一種方案中一個(gè)有價(jià)值的候選藥物，一些研究者已經(jīng)報(bào)告了它的成功應(yīng)用。本項(xiàng)體外研究評(píng)價(jià)了Cangrelor在抗PF4/Hep抗體存在情況下抑制肝素誘發(fā)的血小板聚集的能力。

方法：將30例功能性抗PF4/Hep 抗體陽(yáng)性患者的血小板缺乏性血漿(PPP)與5例健康獻(xiàn)血者血小板富集性血漿(PRP)混合。

在血漿中加入0.5 IU·mL^?1肝素（HIT）后，使用光透射聚集法測(cè)量血小板聚集，并與添加生理鹽水的樣品（對(duì)照組）、加入Cangrelor 500 ng·mL^?1和肝素0.5 IU·mL^?1（處理組）的樣品進(jìn)行比較。組間比較采用Friedman檢驗(yàn)和事后Dunn-Bonferroni檢驗(yàn)。

結(jié)果：肝素0.5 IU·mL^?1觸發(fā)了44種PPP-PRP混合物中的22種發(fā)生聚集，中位數(shù)聚集率為86%（四分位間距[IQR]，69-91）。這22個(gè)陽(yáng)性樣本各自對(duì)照試驗(yàn)的中位數(shù)聚集率為22%（IQR，16-30）（P<0.001）。Cangrelor處理的樣本的中位數(shù)聚集率為29%（IQR，19–54），顯著低于HIT樣本（P<0.001）。Cangrelor抑制肝素誘導(dǎo)的血小板聚集的中位數(shù)為91%（IQR，52-100）。在22個(gè)陽(yáng)性樣本中有10例（45%）樣本，Cangrelor抑制肝素誘發(fā)的血小板聚集＞95%。在22個(gè)陽(yáng)性樣本中有5個(gè)(22%)樣本，Cangrelor抑制肝素誘發(fā)的血小板聚集<50%；有3例樣本(14%)，Cangrelor抑制肝素誘發(fā)的血小板聚集<10%。

結(jié)論：本項(xiàng)體外研究發(fā)現(xiàn)，在抗PF4/Hep抗體存在的情況下，Cangrelor并非肝素誘發(fā)血小板聚集的可靠抑制劑。我們的結(jié)論是，Cangrelor不應(yīng)作為標(biāo)準(zhǔn)抗血小板聚集藥用于心臟病患者，其手術(shù)期間受HIT影響。除非Cangrelor對(duì)特定患者的療效已在術(shù)前血小板聚集試驗(yàn)中得到確認(rèn)，否則應(yīng)選擇其他方案。

文獻(xiàn)來(lái)源：Emmanuelle Scala, MD,Christiane Gerschheimer,Francisco J. Gomez,Lorenzo Alberio, MD,and Carlo Marcucci, MD.Potential and Limitations of the New P2Y12 Inhibitor, Cangrelor, in Preventing Heparin-Induced Platelet Aggregation During Cardiac Surgery: An In Vitro Study.[J]Anesth Analg 2020;131:622–30.

Potential and Limitations of the New P2Y12 Inhibitor, Cangrelor, in Preventing Heparin-Induced Platelet Aggregation During Cardiac Surgery: An In Vitro Study

Abstract

BACKGROUND: Heparin-induced thrombocytopenia (HIT) can put cardiac surgery patients at a high risk of lethal complications. If anti-PF4/heparin antibodies (anti-PF4/Hep Abs) are present, 2 strategies exist to prevent intraoperative aggregation during bypass surgery: first, using an alternative anticoagulant, and second, using heparin combined with an antiaggregant. The new P2Y12 inhibitor, cangrelor, could be an attractive candidate for the latter strategy; several authors have reported its successful use. The present in vitro study evaluated cangrelor’s ability to inhibit heparin-induced platelet aggregation in the presence of anti-PF4/Hep Abs.

METHODS: Platelet-poor plasma (PPP) from 30 patients with functional anti-PF4/Hep Abs was mixed with platelet-rich plasma (PRP) from 5 healthy donors.

Light transmission aggregometry was used to measure platelet aggregation after adding 0.5 IU·mL?1 of heparin (HIT) to the plasma, and this was compared with samples spiked with normal saline (control) and samples spiked with cangrelor 500 ng·mL?1 and heparin 0.5 IU·mL?1(treatment). Friedman test with post hoc Dunn-Bonferroni test was used for between-group comparisons.

RESULTS: Heparin 0.5 IU·mL?1 triggered aggregation in 22 of 44 PPP–PRP mixtures, with a median aggregation of 86% (interquartile range [IQR], 69–91). The median aggregation of these 22 positive samples’ respective control tests was 22% (IQR, 16–30) (P < .001). Median aggregation in the cangrelor-treated samples was 29% (IQR, 19–54) and significantly lower than the HIT samples (P < .001). Cangrelor inhibited heparin-induced aggregation by a median of 91% (IQR, 52–100). Cangrelor only reduced heparin-induced aggregation by >95% in 10 of the 22 positive samples (45%). Cangrelor inhibited heparin induced aggregation by <50% in 5 of the 22 positive samples (22%) and by <10% in 3 samples (14%).

CONCLUSIONS: This in vitro study found that cangrelor was an unreliable inhibitor of heparin-induced aggregation in the presence of anti-PF4/Hep Abs. We conclude that cangrelor should not be used as a standard antiaggregant for cardiac patients affected by HIT during surgery. Unless cangrelor’s efficacy in a particular patient has been confirmed in a presurgery aggregation test, other strategies should be chosen.