Production of anti-PF4 antibodies in antiphospholipid antibody-positive patients is not affected by COVID-19 vaccination

Antibodies against cationic platelet chemokine, platelet factor 4 (PF4/CXCL4), have been described in heparin-induced thrombocytopenia (HIT), but also in patients positive for antiphospholipid antibodies (aPL) even in the absence of heparin treatment and HIT-related clinical manifestations. Anti-PF4 antibodies have been recently described also in subjects who developed thrombosis with thrombocytopenia syndrome (TTS) in association with adenoviral vector-based, but not with mRNA-based,COVID-19 vaccines.
Objective. To investigate whether COVID-19 vaccination affects the production of anti-PF4 antibodies in aPL-positive patients and in control groups.
Methods. Anti-PF4immunoglobulins were detected in patients’ and controls’ serum samples by ELISA and their ability to activate normal platelets was assessed by the platelet aggregation test.
Results. Anti-PF4 were found in 9 of 126 aPL-positive patients, 4 of 50 patients with COVID-19, 9 of 49 with other infections, and 1 of 50 aPL-negative patients with systemic lupus erythematosus. Clinical manifestations of TTS were not observed in any aPL patient positive for anti-PF4, whose serum failed to cause platelet aggregation. The administration of COVID-19 vaccines did not affect the production of anti-PF4 immunoglobulins or their ability to cause platelet aggregation in 44 aPL-positive patients tested before and after vaccination.
Conclusions. Heparin treatment-independent anti-PF4 antibodies can be found in aPL-positive patients and asymptomatic carriers, but their presence, titre as well as in vitro effect on platelet activation are not affected by COVID-19 vaccination.

针对阳离子血小板趋化因子、血小板因子4（platelet factor 4, PF4/CXCL4）的抗体，不仅在肝素诱导的血小板减少症（heparin-induced thrombocytopenia, HIT）中被报道，也可见于抗磷脂抗体（antiphospholipid antibodies, aPL）阳性且无肝素治疗及HIT相关临床表现的患者。近期研究还发现，在接种腺病毒载体新冠疫苗后出现血栓性血小板减少综合征（thrombosis with thrombocytopenia syndrome, TTS）的受试者体内可检测到抗PF4抗体，而接种mRNA新冠疫苗者中未发现此类情况。
研究目的：探究新冠疫苗接种是否会影响抗磷脂抗体阳性患者及对照组体内抗PF4抗体的产生水平。
研究方法：采用酶联免疫吸附试验（ELISA）检测患者与对照血清中的抗PF4免疫球蛋白，并通过血小板聚集试验评估其激活正常血小板的能力。
研究结果：在126例抗磷脂抗体阳性患者中检出9例抗PF4抗体阳性，50例新冠感染患者中4例阳性，49例其他感染患者中9例阳性，50例抗磷脂抗体阴性的系统性红斑狼疮患者中1例阳性。抗PF4抗体阳性的抗磷脂抗体患者均未出现TTS相关临床表现，其血清无法诱导血小板聚集。在接种前后接受检测的44例抗磷脂抗体阳性患者中，新冠疫苗接种并未影响抗PF4免疫球蛋白的产生水平，亦未改变其诱导血小板聚集的能力。
研究结论：无需肝素治疗的抗PF4抗体可在抗磷脂抗体阳性患者及无症状携带者中检出，但新冠疫苗接种并不会影响此类抗体的存在、滴度及其体外对血小板激活的作用。