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Abstract：
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.
摘要：
肝素诱导的血小板减少症（HIT）是针对肝素和血小板因子4（PF4）复合物的抗体介导的免疫反应。肝素和PF4之间的静电相互作用对于在HIT中看到的抗PF4/肝素抗体应答是关键的。金属阳离子与肝素的结合诱导肝素分子的构象变化和电荷中和，和阳离子肝素结合可以调节对肝素结合配偶体的特异性和亲和力。然而,金属阳离子结合肝素在抗PF4/肝素抗体应答中的作用尚未确定.这里,我们利用电感耦合等离子体质谱(ICP-MS)对患者血浆中的16种金属阳离子进行了定量,并在接受肝素治疗的患者队列中检测了临床怀疑HIT后与抗PF4/肝素IgG水平和血小板计数的相关性.该队列（n=32）的平均年龄为60.53（SD=14.31）岁，平均抗PF4/肝素抗体光密度[OD405]为0.93（SD=1.21）单位，主要为女性（n=23）。抗PF4/肝素抗体检测结果阳性（OD405≥0.5单位）的患者年龄较小，增加了体重和BMI，并且与抗体阴性患者相比，更可能具有阳性的5-羟色胺释放测定（SRA）结果。我们观察到抗体阳性和阴性组之间钠和铝的统计学差异以及抗PF4/肝素抗体水平与钠和银的显着相关性。虽然钠浓度的差异与抗体阳性状态相关，并且与抗体水平相关。未进行复制。需要额外的研究来证实我们观察到的关联，包括体外结合研究和更大的观察队列。
