Background: Daratumumab is a human monoclonal antibody used for the treatment of multiple myeloma, which binds to CD38, a protein that is expressed on red blood cells (RBCs). Therefore, the plasma of these patients reacts with the RBCs producing a panreactivity and interfering in the transfusion compatibility testing. Panagglutination may persist for up to 6 months after the last infusion of daratumumab. An anti-CD38 antibody for treatment of multiple myeloma shows a strong interference in the indirect antiglobulin test (IAT) where most of the reactions turn to unspecifically (wrong) positive. The time consuming standard technique using Dithiothreitol (DTT) counteracts the interference but has major drawbacks like destruction of Kel antigens or hemolysis. The DaraEx ® compound inhibits the agglutination effect of anti-CD38 in IAT without side effects. DaraEx ® is a neutralizing agent for the inhibition of the agglutination effect of the anti-CD38 antibody daratumumab in IAT. Aims: To validate the procedure to resolve the interference of daratumumab in transfusion compatibility testing using red cells treated with DaraEx ® for the inhibition of the agglutination effect of the anti-CD38 antibody daratumumab in IAT. Daratumumab can interfere with crossmatching and antibody screening in the IAT, which will allow us to identify a clinically significant antibody that has been initially masked by the presence of daratumumab. Methods: The study has been conducted in 25 plasma samples of patients diagnosed with multiple myeloma who have been treated with daratumumab. Irregular antibody screening tests and CrossMatching were performed on all of them, being positive in all cases. We performed the technique to eliminate reactivity by treating the red cells used in compatibility tests with DaraEx ® , which neutralizes CD38 on the surface of the erythrocyte, thereby preventing Daratumumab from binding and inducing agglutination. The material used was DaraEx ® , 0.9% NaCl LISS/Coombs ID-Cards and Test cell reagents for the ID-System; We performed the method in Biovue Column Agglutination Technology and gel card systems. Results: After performing the technique, we were able to eliminate panreactivity in both Irregular antibody screening tests and CrossMatching. Summary/Conclusion: Daratumumab causes panreactivity in vitro by binding to CD38 on reagent RBCs. It is necessary to do a baseline antibody screen (type and screen) before starting the treatment with daratumumab. Treating reagent RBCs with DaraEx ® is a useful easy and quick method to mitigate the interference created by antiCD38 mAbs in pretransfusion testing. DaraEx is a quick and simple procedure; it doesn't affect other antigens or alloantibody reactions. It doesn't have side effects like destruction of blood group antigens or hemolysis as described for the standard DTT treatment. Therefore, we consider it a very useful technique to resolve interferences produced by daratumumb with blood compatibility testing. We believe that it is essential to have a validated techni...

A nonsmoking patient with gastroesophageal reflux disease and Raynaud disease had 4 weeks of dysphagia and a 4.54-kg weight loss over 3 months, cough productive of yellow sputum, and dyspnea on exertion. White blood cell count and creatine kinase and aldolase levels were elevated; antinuclear antibody assay findings were positive; and chest CT showed bibasilar pulmonary consolidations and ground glass opacities. What is the diagnosis and what would you do next?

Lithium is one of the first-line agents for treating bipolar disorder. Although this agent is highly effective in treating mood disorders, renal toxicity is a frequent side effect. Lithium metabolism is affected by sodium-lithium counter-transporter (SLC-T) in erythrocytes. The high activity of SLC-T can result in decreased urinary lithium clearance and may lead to accumulation of lithium in the distal renal tubular cells, causing lithium toxicity. SLC-T is a genetic marker in primary hypertension (HTN), HTN in pregnancy, diabetic nephropathy, and IgA nephropathy (IgA-N) with HTN. Patients with IgA-N have been reported to have enhanced SLC-T activity and are likely to have considerably lower renal fractional clearance of lithium. Therefore, patients taking lithium for bipolar disorder with coexisting IgA-N can have severe lithium-induced nephropathy and nephrotoxicity even at therapeutic serum levels. Serum lithium levels reflect only extracellular lithium concentration. However, lithium exerts its effects once it has moved to the intracellular compartment. This phenomenon illustrates the reason why patients with significantly elevated serum levels might be asymptomatic. Creatinine clearance is inversely related to the duration of lithium therapy. The degree of interstitial fibrosis on renal biopsy has been known to be associated with the duration of lithium therapy and cumulative dose. We present a case with a past medical history of bipolar disorder treated with lithium for almost 20 years. His family history was significant for HTN. The patient was diagnosed with renal insufficiency of unknown causes, for which he underwent renal biopsy. The renal biopsy showed a typical lithium-induced tubulointerstitial nephritis and a coincidental finding of IgA-N. We suspect a high activity of SLC-T seen in IgA-N, and the adverse effects of lithium on SLC-T activity might cause reduction of urinary lithium clearance and accumulation of lithium in distal renal tubular cells, contributing to nephrotoxicity. There is a lack of the literature on the coexistence of IgA-N and lithium nephrotoxicity. We recommend in patients with concomitant IgA-N, taking lithium, more frequent monitoring of renal functions, and dose adjustments may reduce the risk of lithium-induced nephrotoxicity.