Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia.
Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia.
复制标题
DOI：
10.1097/moh.0000000000000066
复制
发表时间：
2014-09
影响因子：
3.2
通讯作者：
Sachais BS
中科院分区：
文献类型：
--
作者：
McKenzie SE;Sachais BS
综述肝素诱导的血小板减少症(HIT)的病理生理学研究的最新进展，并将其应用于疑似HIT和确诊HIT患者的治疗。HIT的病理生理学是动态的、复杂的。HIT的病理生理学是由四种基本成分--肝素(HEP)、血小板第4因子(Pf4)、抗HEP-Pf4复合体的Ig G抗体和血小板FcγRIA启动的。HIT由活化的血小板、单核细胞、内皮细胞和凝血蛋白传播。对独特的HIT抗体反应的见解不断涌现，但对于B细胞、T细胞和抗原提呈细胞的相对作用还没有达成共识。通过FcγRIIA激活血小板，这是HIT的必要条件，已经得到了更好的认识。由于几个原因，治疗仍然具有挑战性。由于HEP的广泛使用以及当前诊断测试和评分系统的不足，疑似HEP的发生率高于已证实的HEP。在已证实的HIT中，批准的治疗可以减少但不能消除血栓形成，并有实质性的出血风险。理性的新治疗策略，针对HIT病理生理学的启动步骤，并随着时间的推移而进行潜在的组合，正处于不同的开发阶段。在理解HIT中分子和细胞玩家的广度方面继续取得进展。需要转变为改进诊断和治疗。
To review the recent developments in understanding the pathophysiology of heparin-induced thrombocytopenia (HIT) and in applying this knowledge to the treatment of patients with suspected and proven HIT. HIT pathophysiology is dynamic and complex. HIT pathophysiology is initiated by four essential components – heparin (Hep), platelet factor 4 (PF4), IgG antibodies against the Hep–PF4 complex, and platelet FcγRIIa. HIT is propagated by activated platelets, monocytes, endothelial cells, and coagulation proteins. Insights into the unique HIT antibody response continue to emerge, but without consensus as to the relative roles of B cells, T cells, and antigen-presenting cells. Platelet activation via FcγRIIa, the sine qua non of HIT, has become much better appreciated. Therapy remains challenging for several reasons. Suspected HIT is more frequent than proven HIT, because of the widespread use of Hep and the inadequacies of current diagnostic tests and scoring systems. In proven HIT, approved treatments reduce but do not eliminate thrombosis, and have substantial bleeding risk. Rational novel therapeutic strategies, directed at the initiating steps in HIT pathophysiology and with potential combinations staged over time, are in various phases of development. Progress continues in understanding the breadth of molecular and cellular players in HIT. Translation to improved diagnosis and treatment is needed.