Acquired Coagulopathy With Immune Checkpoint Inhibitors: An Underrecognized Association Between Inflammation and Coagulation

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusions: Recognition of acquired coagulopathy as a complication of immunotherapy and its aggressive management are crucial to reduce morbidity and mortality associated with this condition.

Keywords

• Immune checkpoint inhibitors
• Immunotherapy
• Acquired coagulopathy
• Disseminated intravascular coagulation
• Inflammatory coagulopathy