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We had a melanoma patient on Nivolumab = Opdivo who apparently has hemolytic anemia but his IgG was only microscopically positive and his complement was negative. Hgb 5.5. Retic % slightly elevated, absolute retic normal, immature fraction retic very high. Bili and LDH normal. Hpt <14 and responded to steroids. They blamed this drug so I hunted up this article. This was new to me so I wanted to share it. Clinical Trial Am J Hematol 2019 May;94(5):563-574. doi: 10.1002/ajh.25448. Epub 2019 Mar 13. Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors Rebecca Karp Leaf 1, Christopher Ferreri 2, Deepa Rangachari 3, James Mier 3, Wesley Witteles 4, George Ansstas 5, Theodora Anagnostou 6, Leyre Zubiri 1, Zofia Piotrowska 1, Thein H Oo 7, David Iberri 8, Mark Yarchoan 9, April K S Salama 10, Douglas B Johnson 11, Andrew D Leavitt 12, Osama E Rahma 13, Kerry L Reynolds 1, David E Leaf 14 PMID: 30790338 DOI: 10.1002/ajh.25448 Free article Abstract Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were re-challenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are re-challenged with an ICPi do not appear to develop recurrence of AIHA.

Once you've called a critical value of something that doesn't change rapidly, like a very low platelet, red cell or white cell count, you don't need to keep calling every subsequent value, since the ordering physician/NP/PA has the responsibility of checking lab values for studies they order. Not the lab. Plus it's a waste of everyone's time and annoying :). Not a big fan of critical values in general, particularly for non-emergent metrics like cell counts, creatinine, BUN, etc. Usually the clinical situation is vastly more important than any laboratory number, including for the CBC and chemistries other than electrolytes. One of the big time wasters in laboratory and clinical medicine. Only unexpected values that need action within minutes to hours need to be "critical" and called in my view. Blood cell counts aren't among them in my view. There's nothing critical about a white cell count of 500 or 100. Presence of blasts is another story.

When using Immucor Solid Phase I have Rapid ID, Extend I (all Rh+ cells w 5-6 c neg and e neg cells), Extend II (all Rh neg cells w 1 Rh+) 3% panels: Immucor Panocell (10 cells + 1 rare cell). Used to use Ortho 0.8% panel A and Panel B BioRad has 3% and 0.6% panels

The mechanisms of what have been termed TRALI (actually a subset of acute lung injury/acute respiratory distress syndrome) and TACO (actually something very common, congestive heart failure) have been widely misunderstood due to unjustified assumptions/dogma. There are many biologic mediators other than antibodies that can cause lung injury after venous infusion which directly subjects the lung vascular endothelium to these mediators (antibodies, activated cells, lipids, mediators such as sCD40L, DNA/histones). Likewise there are many mediators that can cause or exacerbate cardiac failure after venous infusion (inflammatory mediators, excess volume). Cardiac failure is not just volume overload, but can be caused by fever, inflammatory cytokines and vascular/myocardial muscle dysfunction. The notion that these are distinct entities is also at variance with clinical experience. Many patients have signs of both cardiac failure and pulmonary failure simultaneously. So the definitions and pathophysiology used in reviews and texts are lacking in validity and just plain oversimplified and wrong, in my view. There are compelling data to support these iconoclastic contentions for TRALI, and some for TACO. Most germane (see attachment), when we introduced universal leukoreduction, we saw a sustained 83% drop in reports of TRALI and 50% in TACO over the following years. This suggests that white cells/DNA/histones play a role in causing lung and heart inflammation and dysfunction. This clinical observation was confirmed in animal studies from Denisa Wagner's lab at Harvard demonstrating that neutrophil extracellular traps (NETS) infused intravenously can cause acute lung injury (see attachment). To me these observations are convincing evidence that leukoreduction alters cardiorespiratory injury and failure post-transfusion and represents one of the strongest arguments for universal leukoreduction. Needless to say, this challenge to dogma has been ignored by the transfusion medicine community which continues, at least in the USA, to infuse deadly white cells and their degradation products (free DNA/histones) to patients, one of the great tragedies of the last 20 years in the USA blood bank field. We got this entirely wrong and tens of thousands of patients have probably died unnecessarily due to complications of non-leukoreduced transfusions. ULR TRALI TACO PMC version.pdf NETS and TRALI Wagner 2012.pdf

Hello RRay, Welcome to PathLabTalk. Please feel free to browse around and get to know the others. If you have any questions, please don't hesitate to ask. RRay joined on the 01/26/2022. View Member

Can anyone explain the justification for irradiating liquid plasma (never frozen) used for trauma patients when we don't irradiate the red cell units they get? I know the RBCs are leukoreduced so don't contain many viable lymphocytes but there were cases of GVHD if LR units weren't irradiated. Our liquid plasma is made using a hard spin so I would think that there aren't many WBCs in it but no one seems to be able to tell me how the number of lymphocytes in liquid plasma compares to the number in a LR red cell unit. Maybe this is because the big places irradiating their plasma have their own irradiators. For us, it would nearly double the price of the plasma unit so I need justification.

I very much appreciate you taking the time to answer my question, and in such a detailed, but still easily understood manner. Thank you very much Neil.

Hi @Ensis01, @Mabel Adams was referring to irradiating liquid plasma for trauma patients. You may or may not know the immune state of the patient when issuing. Liquid plasma is likely leukoreduced, but it's never frozen, so there may be viable WBCs; hence, irradiation.

The company told us. And really, it does make sense. We are testing the sensitivity of the reagents in the cards by sending a coated cell from the reaction chamber down through the reagent/gel. It shouldn't matter if the cell was coated a few minutes ago or a few days ago, the IGG Card is working.