Joseph Jacinth J, Rajan Arun, Gulley James L, Ito Sawa, Kessler Craig M
Cellular Therapy Branch, National Heart, Lung, and Blood Institutes, Bethesda, Maryland.
Department of Hematology/Oncology, Medstar Washington Hospital Center, Georgetown University, Washington, District of Columbia.
JTO Clin Res Rep. 2020 May 4;1(3):100049. doi: 10.1016/j.jtocrr.2020.100049. eCollection 2020 Sep.
Immune-related adverse events affecting virtually every organ system have been described in individuals receiving immune checkpoint inhibitors. The spectrum of hematologic adverse effects is diverse and includes autoimmune cytopenias, hemolysis, or inhibition of coagulation factors. The interplay of inflammation and the coagulation cascade is complex, and immune checkpoint inhibitors can induce coagulopathy by disrupting the intricate link between these pathways.
We report acquired coagulopathy in two patients treated with the programmed death-ligand 1 antibodies, atezolizumab and avelumab, respectively. Clinical findings and results of extensive laboratory workup are reported. We hypothesize that cytokine release is a potential pathologic mechanism responsible for acquired coagulopathy.
Symptoms included fever, fatigue, and disorientation in one patient and fever, myalgias, and skin rash in the other. Laboratory features included an abnormal coagulation profile; low fibrinogen levels; and elevated D-dimer, ferritin, and triglycerides. Treatment consisted of intravenous glucocorticoids in both cases and the use of fresh frozen plasma, cryoprecipitate, and clotting factor support in one patient.
Recognition of acquired coagulopathy as a complication of immunotherapy and its aggressive management are crucial to reduce morbidity and mortality associated with this condition.
在接受免疫检查点抑制剂治疗的个体中，已描述了几乎影响每个器官系统的免疫相关不良事件。血液学不良反应的范围多种多样，包括自身免疫性血细胞减少、溶血或凝血因子抑制。炎症与凝血级联反应之间的相互作用很复杂，免疫检查点抑制剂可通过破坏这些途径之间的复杂联系而诱发凝血病。
我们报告了分别接受程序性死亡配体1抗体阿特珠单抗和阿维鲁单抗治疗的两名患者发生的获得性凝血病。报告了临床发现和广泛实验室检查的结果。我们假设细胞因子释放是获得性凝血病的一种潜在病理机制。
一名患者的症状包括发热、疲劳和定向障碍，另一名患者的症状包括发热、肌痛和皮疹。实验室检查特征包括凝血指标异常；纤维蛋白原水平低；以及D-二聚体、铁蛋白和甘油三酯升高。两名患者均接受了静脉糖皮质激素治疗，其中一名患者还使用了新鲜冰冻血浆、冷沉淀和凝血因子支持治疗。
认识到获得性凝血病是免疫治疗的一种并发症并对其进行积极管理，对于降低与该病症相关的发病率和死亡率至关重要。
