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Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström macroglobulinemia (WM). The autoimmune disorders are primarily mediated by autoimmune monoclonal gammopathy, but drug-induced hemolysis should also be considered. Herein, we presented the case of a 63-year-old female WM patient complicated with ITP, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1-2×10 9 /L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, secondary AITP and AIHA, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis relieved three days after eltrombopag withdrawal. This is the first report on eltrombopag-induced AIHA in the management of WM-associated ITP., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 Shen et al.)

Objective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design., Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated., Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68-0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71-0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses., Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Ye et al.)