Rauova L, Arepally G, McKenzie S E, Konkle B A, Cines D B, Poncz M
Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1(0 1):249-52. doi: 10.1111/j.1538-7836.2009.03373.x.
Heparin-induced thrombocytopenia (HIT) is an iatrogenic disorder that occurs in a small subset of patients receiving heparin. Twenty-five per cent (or higher) of affected patients develop limb or life-threatening thrombosis. The effectiveness of therapy is incomplete and may be complicated by bleeding. HIT is caused by antibodies that recognize the platelet chemokine, Platelet Factor 4 (PF4), complexed to heparin or to cellular glycosaminoglycans (GAGs). However, antibodies with the same apparent specificity are found in many more patients without clinical disease and the reason why so few develop HIT is uncertain. We propose that HIT antibodies recognize cell surface PF4/GAG complexes on intravascular cells, including platelets and monocytes that are dynamic and mutable. Heparin removes cell surface-bound PF4 in most individuals, but removal is incomplete in those with high pre-exposure surface-bound PF4 levels. Such individuals retain critically localized cellular antigenic complexes at the time antibodies develop and are at risk to develop HIT. This article reviews the scientific basis for this model and its clinical implications.
肝素诱导的血小板减少症（HIT）是一种医源性疾病，发生于一小部分接受肝素治疗的患者中。25%（或更高比例）的受影响患者会出现肢体血栓形成或危及生命的血栓。治疗效果并不完全，且可能因出血而复杂化。HIT是由识别与肝素或细胞糖胺聚糖（GAGs）结合的血小板趋化因子血小板因子4（PF4）的抗体引起的。然而，在更多没有临床疾病的患者中也发现了具有相同明显特异性的抗体，而只有极少数人会发生HIT的原因尚不确定。我们提出，HIT抗体识别血管内细胞表面的PF4/GAG复合物，包括动态可变的血小板和单核细胞。在大多数个体中，肝素会清除细胞表面结合的PF4，但在暴露前细胞表面结合PF4水平较高的个体中，清除并不完全。这些个体在抗体产生时保留关键的局部细胞抗原复合物，并有发生HIT的风险。本文综述了该模型的科学依据及其临床意义。
