Prof. Theodore (Ted) E. Warkentin, Hamilton Regional Laboratory Medicine Program, Room 1-270B, Hamilton General Hospital, 237 Barton St. E., Hamilton, Ontario L8L 2X2, Canada, Tel.: +1 905 527 0271 ext. 46139, Fax: +1 905 577 1421, E-mail:
Thromb Haemost. 2016 Oct 28;116(5):813-822. doi: 10.1160/TH16-06-0435. Epub 2016 Sep 22.
HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis.
HIT 是一种获得性抗体介导的疾病，与血栓形成密切相关，包括弥散性血管内凝血（DIC）引起的微血栓形成。从 HIT 的 4Ts 评分系统的角度回顾了 HIT 的临床特征，该系统强调了其血小板减少症发病的特征性时间。HIT 抗体识别血小板因子 4（PF4）/肝素的多分子复合物。然而，一部分 HIT 血清识别与血小板硫酸软骨素结合的 PF4；这些抗体即使在没有肝素的情况下也能在体外和体内激活血小板，从而解释了：迟发性 HIT（HIT 在停止肝素后开始或恶化）；持续性 HIT（HIT 需要数周才能恢复）；自发性 HIT 综合征（一种临床上和血清学上类似于 HIT 的疾病，但没有肝素的近期暴露）；以及磺达肝素相关的 HIT（四种不同的综合征，其特征为血小板减少症，在使用磺达肝素治疗期间开始或恶化），并提出了一个新的患者病例，在使用磺达肝素治疗 HIT 期间持续血小板减少症（和致命性出血），患者血清诱导磺达肝素依赖性血小板激活（“磺达肝素交叉反应”）。具有讽刺意味的是，尽管存在磺达肝素相关的 HIT，但这种五糖抗凝剂是 HIT 的常见治疗方法（包括作者使用的一种）。HIT 可能与其他疾病混淆，包括：a）与 HIT 相似的时间（例如，迟发性阿昔单抗相关的血小板减少症）；b）联合血小板减少症/血栓形成（例如，急性 DIC 和休克肝引起的对称性周围坏疽）；c）发病时间和血栓形成（例如，癌症相关 DIC 并发的华法林相关静脉肢体坏疽）。通过了解 HIT 和非 HIT 模拟疾病之间的临床和病理生理学相似和不同之处，临床医生能够更好地做出正确的诊断。
