Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada; Service of Benign Hematology, Hamilton Health Sciences, Hamilton General Hospital, Hamilton, ON, Canada; McMaster Center for Transfusion Research, McMaster University, Hamilton, ON, Canada.
Semin Hematol. 2022 Apr;59(2):59-71. doi: 10.1053/j.seminhematol.2022.02.005. Epub 2022 Feb 20.
Platelet factor 4 (PF4) is a highly cationic tetrameric protein that can be targeted by platelet-activating anti-PF4 antibodies of immunoglobulin G (IgG) class. Certain features of PF4, including its multivalent nature (duplicate antigen sites per tetramer), the ability of many PF4 tetramers to undergo close approximation through charge neutralization, and the dimeric binding of IgG molecules, results in formation of IgG-containing immune complexes in situ on platelets, neutrophils, and monocytes, resulting in Fcγ receptor-mediated pancellular activation that also activates hemostasis (potential for disseminated intravascular coagulation). This review discusses 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia ([HIT]; triggered by heparin and certain other polyanionic pharmaceuticals, featuring predominantly heparin-dependent antibodies), autoimmune HIT (aHIT; severe subtype of HIT that features both heparin-dependent and heparin-independent platelet-activating antibodies), and spontaneous HIT (non-heparin triggers such as knee replacement surgery and infection; predominantly heparin-independent platelet-activating antibodies). Most recently, a novel fourth anti-PF4 disorder, vaccine-induced immune thrombotic thrombocytopenia (VITT), was identified as an ultrarare complication of adenovirus vector vaccines. VITT is characterized by thrombocytopenia, disseminated intravascular coagulation, a high frequency of thrombosis-including in unusual sites (cerebral veins, splanchnic veins)-and highly pathogenic anti-PF4 antibodies with heparin-independent platelet-activating properties.
血小板因子 4（PF4）是一种高度阳离子的四聚体蛋白，可以被血小板激活的 IgG 类抗 PF4 抗体靶向。PF4 的某些特征，包括其多价性质（每个四聚体有重复的抗原位点）、许多 PF4 四聚体通过电荷中和而接近的能力，以及 IgG 分子的二聚体结合，导致 IgG 免疫复合物在血小板、中性粒细胞和单核细胞原位形成，导致 Fcγ 受体介导的全细胞激活，也激活止血（潜在的弥漫性血管内凝血）。本文综述了 4 种抗 PF4 疾病：经典肝素诱导的血小板减少症（[HIT]；由肝素和某些其他多阴离子药物触发，主要由肝素依赖性抗体引起）、自身免疫性 HIT（aHIT；HIT 的严重亚型，其特征是既有肝素依赖性又有肝素非依赖性血小板激活抗体）和自发性 HIT（非肝素触发，如膝关节置换术和感染；主要由肝素非依赖性血小板激活抗体引起）。最近，一种新的第四种抗 PF4 疾病，疫苗诱导的免疫性血栓性血小板减少症（VITT），被确定为腺病毒载体疫苗的一种罕见并发症。VITT 的特征是血小板减少症、弥漫性血管内凝血、血栓形成的高频率，包括在不常见的部位（脑静脉、内脏静脉），以及具有肝素非依赖性血小板激活特性的高致病性抗 PF4 抗体。
