Warkentin Theodore E
Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.
Department of Medicine, McMaster University, Ontario, Canada.
Int J Lab Hematol. 2025 May 13. doi: 10.1111/ijlh.14486.
The prototypic anti-platelet factor 4 (PF4) disorder-heparin-induced thrombocytopenia and thrombosis (HITT)-features immunoglobulin G (IgG) class antibodies that activate platelets, monocytes, and neutrophils in a mainly heparin-dependent fashion via Fcγ receptor-dependent cellular activation. The identification in 2021 of an ultrarare HITT-mimicking disorder, vaccine-induced immune thrombocytopenia and thrombosis (VITT)-triggered by two different adenoviral vector vaccines-abruptly broadened the spectrum of recognized anti-PF4 disorders.
To classify platelet-activating anti-PF4 disorders, both HITT/HITT-like and VITT/VITT-like.
Literature was reviewed from the perspective of a researcher-clinician involved in identifying novel anti-PF4 disorders.
Atypical presentations of HITT with proximate heparin triggers but which evince heparin-independent platelet-activating properties ("autoimmune HITT") have been recognized since 2001; heparin-independent platelet-activating properties also characterize HITT-mimicking disorders with undefined non-heparin triggers (e.g., post-knee replacement "spontaneous HITT"). Antibodies identical to those of (vaccine-induced) VITT can rarely be triggered by natural adenovirus infection. HITT and VITT antibodies recognize different epitopes on PF4. All the aforementioned anti-PF4 disorders are acute, transient, and self-limited. Recently, however, chronic anti-PF4 disorders featuring potent VITT-like properties of monoclonal proteins (M-proteins) have been identified: this oftentimes treatment-refractory entity, named "VITT-like monoclonal gammopathy of thrombotic significance" (VITT-like MGTS), dramatically expands the clinical spectrum of recognized anti-PF4 disorders. Anti-PF4 disorders with heparin-independent platelet-activating antibodies, whether HITT or VITT, may require management strategies beyond anticoagulation alone, including high-dose intravenous immunoglobulin (IVIG) or (for VITT-like MGTS) the Bruton's tyrosine kinase inhibitor, ibrutinib.
Clinicians and laboratorians require knowledge of the rapidly broadening spectrum of recognized acute and chronic anti-PF4 disorders.
典型的抗血小板因子4（PF4）紊乱——肝素诱导的血小板减少症和血栓形成（HITT）——其特征是免疫球蛋白G（IgG）类抗体通过Fcγ受体依赖性细胞活化，以主要依赖肝素的方式激活血小板、单核细胞和中性粒细胞。2021年发现了一种极其罕见的类似HITT的紊乱，即疫苗诱导的免疫性血小板减少症和血栓形成（VITT），由两种不同的腺病毒载体疫苗引发，这突然拓宽了已确认的抗PF4紊乱的范围。
对血小板活化的抗PF4紊乱进行分类，包括HITT/HITT样和VITT/VITT样。
从参与识别新型抗PF4紊乱的研究人员兼临床医生的角度对文献进行综述。
自2001年以来，已认识到具有近期肝素触发因素但表现出肝素非依赖性血小板活化特性的HITT非典型表现（“自身免疫性HITT”）；肝素非依赖性血小板活化特性也是具有未明确非肝素触发因素的类似HITT紊乱的特征（例如，膝关节置换术后的“自发性HITT”）。与（疫苗诱导的）VITT相同的抗体很少由天然腺病毒感染触发。HITT和VITT抗体识别PF4上不同的表位。上述所有抗PF4紊乱都是急性、短暂且自限性的。然而，最近已发现具有单克隆蛋白（M蛋白）类似VITT的强效特性的慢性抗PF4紊乱：这种通常对治疗难治的实体，称为“具有血栓形成意义的VITT样单克隆丙种球蛋白病”（VITT样MGTS），极大地扩展了已确认的抗PF4紊乱的临床范围。具有肝素非依赖性血小板活化抗体的抗PF4紊乱，无论是HITT还是VITT，可能都需要除单纯抗凝之外的管理策略，包括大剂量静脉注射免疫球蛋白（IVIG）或（对于VITT样MGTS）布鲁顿酪氨酸激酶抑制剂伊布替尼。
临床医生和实验室人员需要了解已确认的急性和慢性抗PF4紊乱迅速拓宽的范围。
