Dataset Information

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.

SUBMITTER: Joseph JJ

PROVIDER: S-EPMC8474288 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) treat an expanding range of cancers. Consistent basic data suggest that these same checkpoints are critical negative regulators of atherosclerosis. Therefore, our objectives were to test whether ICIs were associated with accelerated atherosclerosis and a higher risk of atherosclerosis-related cardiovascular events.MethodsThe study was situated in a single academic medical center. The primary analysis evaluated whether exposure to an ICI was associated with atherosclerotic cardiovascular events in 2842 patients and 2842 controls matched by age, a history of cardiovascular events, and cancer type. In a second design, a case-crossover analysis was performed with an at-risk period defined as the 2-year period after and the control period as the 2-year period before treatment. The primary outcome was a composite of atherosclerotic cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke). Secondary outcomes included the individual components of the primary outcome. In addition, in an imaging substudy (n=40), the rate of atherosclerotic plaque progression was compared from before to after the ICI was started. All study measures and outcomes were blindly adjudicated.ResultsIn the matched cohort study, there was a 3-fold higher risk for cardiovascular events after starting an ICI (hazard ratio, 3.3 [95% CI, 2.0-5.5]; P<0.001). There was a similar increase in each of the individual components of the primary outcome. In the case-crossover, there was also an increase in cardiovascular events from 1.37 to 6.55 per 100 person-years at 2 years (adjusted hazard ratio, 4.8 [95% CI, 3.5-6.5]; P<0.001). In the imaging study, the rate of progression of total aortic plaque volume was >3-fold higher with ICIs (from 2.1%/y before 6.7%/y after). This association between ICI use and increased atherosclerotic plaque progression was attenuated with concomitant use of statins or corticosteroids.ConclusionsCardiovascular events were higher after initiation of ICIs, potentially mediated by accelerated progression of atherosclerosis. Optimization of cardiovascular risk factors and increased awareness of cardiovascular risk before, during, and after treatment should be considered among patients on an ICI.