Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
J Thromb Haemost. 2013 Feb;11(2):253-60. doi: 10.1111/jth.12098.
Anti-PF4/heparin antibodies are frequently generated after coronary artery bypass grafting (CABG) surgery, with platelet-activating IgG implicated in heparin-induced thrombocytopenia (HIT). It is controversial whether non-platelet-activating antibodies are associated with thrombosis.
To determine in post-CABG patients whether thromboprophylaxis using fondaparinux vs. unfractionated heparin (UFH) reduces the frequency of anti-PF4/heparin antibodies, and whether anti-PF4/heparin antibodies are associated with early graft occlusion.
METHODS/PATIENTS: In a pre-planned secondary analysis of a randomized control trial (RCT) comparing fondaparinux vs. UFH thromboprophylaxis post-CABG, we determined the frequency of anti-PF4/heparin antibody formation by solid-phase enzyme-immunoassay (EIA) and of platelet-activating antibodies by serotonin-release assay (SRA); the SRA and fluid-phase EIA were used to assess fondaparinux cross-reactivity. We also examined whether anti-PF4/heparin antibodies were associated with early arterial or venous graft occlusion (6-week CT angiography).
We found no significant difference in the frequency of antibody formation between patients who received fondaparinux vs. UFH (65.3% vs. 46.0%; P = 0.069), and no significant fondaparinux cross-reactivity. Venous graft occlusion(s) occurred in 6/26 patients who formed 'strong' IgG antibodies (≥ 1.0 optical density [OD] units and ≥ 2× baseline) vs. 3/66 who did not (P = 0.0139). In both unadjusted and adjusted analyses, strong postoperative (but not pre-operative) anti-PF4/heparin IgG responses were associated with a markedly increased risk of early venous (but not arterial) graft occlusion (adjusted OR, 9.25 [95% CI, 1.73, 49.43]; P = 0.0093); notably, none of the three SRA-positive patients developed a venous graft occlusion.
Fondaparinux vs. UFH thromboprophylaxis postCABG does not reduce anti-PF4/heparin antibody formation. Non-platelet-activating anti-PF4/heparin IgG antibodies generated post operatively are associated with early venous graft occlusion.
在冠状动脉旁路移植术（CABG）手术后，经常会产生抗 PF4/肝素抗体，血小板激活 IgG 与肝素诱导的血小板减少症（HIT）有关。非血小板激活抗体是否与血栓形成有关存在争议。
在 CABG 术后患者中，确定使用磺达肝素钠与未分级肝素（UFH）进行血栓预防治疗是否会降低抗 PF4/肝素抗体的频率，以及抗 PF4/肝素抗体是否与早期移植物闭塞有关。
方法/患者：在一项比较 CABG 后磺达肝素钠与 UFH 血栓预防治疗的随机对照试验（RCT）的预先计划的二次分析中，我们通过固相酶免疫测定（EIA）确定抗 PF4/肝素抗体形成的频率，并通过 5-羟色胺释放测定（SRA）确定血小板激活抗体的频率；SRA 和液相结合 EIA 用于评估磺达肝素钠的交叉反应性。我们还检查了抗 PF4/肝素抗体是否与早期动脉或静脉移植物闭塞（6 周 CT 血管造影）有关。
我们发现接受磺达肝素钠与 UFH 的患者之间抗体形成的频率没有显著差异（65.3% vs. 46.0%；P = 0.069），并且没有明显的磺达肝素钠交叉反应性。在形成“强”IgG 抗体（≥ 1.0 光密度[OD]单位和≥ 2×基线）的 26 名患者中，有 6 名（6/26）发生静脉移植物闭塞（s），而在未形成抗体的 66 名患者中，有 3 名（3/66）发生静脉移植物闭塞（P = 0.0139）。在未调整和调整分析中，术后（而非术前）的强抗 PF4/肝素 IgG 反应与早期静脉（而非动脉）移植物闭塞的风险显著增加相关（调整后的 OR，9.25 [95%CI，1.73，49.43]；P = 0.0093）；值得注意的是，三名 SRA 阳性患者均未发生静脉移植物闭塞。
CABG 术后磺达肝素钠与 UFH 血栓预防治疗并不能降低抗 PF4/肝素抗体的形成。术后产生的非血小板激活的抗 PF4/肝素 IgG 抗体与早期静脉移植物闭塞有关。
