Centre for Clinical Transfusion Medicine, Medical Faculty of Tübingen, University of Tübingen.
Haematologica. 2022 Jun 1;107(6):1264-1277. doi: 10.3324/haematol.2021.279484.
Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient's condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.
几种治疗药物可通过免疫或非免疫机制引起血小板减少症。非免疫介导的血小板减少症是由于药物分子对血小板或巨核细胞的直接毒性所致。另一方面,免疫介导的血小板减少症涉及到形成针对血小板特异性糖蛋白复合物的抗体,如经典的药物诱导的免疫性血小板减少症(DITP),或针对血小板因子 4,如肝素诱导的血小板减少症(HIT)和疫苗诱导的免疫性血栓性血小板减少症(VITT)。临床症状包括血小板计数迅速下降、出血或血栓形成。由于患者的病情可能迅速恶化,因此及时诊断和治疗至关重要。然而,必要的诊断测试仅在专门的实验室中可用。因此,治疗中最具挑战性的步骤是确定导致血小板减少症的药物,这通常很困难,因为许多患者正在服用多种药物,并且存在可能导致血小板减少症的合并症。虽然 DITP 通常与出血风险增加有关,但 HIT 和 VITT 由于血栓栓塞并发症的高发生率,死亡率很高。对药物相关血小板减少症/血栓形成进行结构化处理可导致成功治疗和降低死亡率。除了描述 DITP、HIT、VITT 和疫苗相关免疫性血小板减少症的治疗方法外,本综述还提供了正确管理患者所需的病理生理学和临床信息。