Warm Autoimmune Hemolytic Anemia with a Direct Antiglobulin Test Positive for C3 and Negative for IgG: A Case Study and Analytical Literature Review of Incidence and Severity

Palla, Amruth R.; Khimani, Farhad; Craig, Michael

doi:10.4137/ccrep.s11469

Cited by 9 publications

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“…Warm AIHA is generally mediated via IgG that binds the Fc receptor of phagocytic cells, but can also rarely be mediated by IgM, IgA, or a combination of these 3 antibodies or via C3 alone [6], and the autoantibodies are active at temperatures greater than 37°C [7]. Cold AIHA results from IgM activation of classic complement pathway and the autoantibodies are active at temperatures of 0–4°C [7].…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy

et al. 2016

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Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al.: BMC Med 2016;14: 20], metastatic non-small cell lung cancer [Guibert and Mazières: Expert Opin Biol Ther 2015;15: 1789–1797], metastatic renal cell cancer [Farolfi et al.: Expert Opin Drug Metab Toxicol 2016;12: 1089–1096], and relapsed or refractory classic Hodgkin’s lymphoma [Villasboas and Ansell: Expert Rev Anticancer Ther 2016;16: 5–12]. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently [Kong et al.: Melanoma Res 2016;26: 202–204; Schwab et al.: Case Rep Oncol 2016;9: 373–378; Tardy et al.: Hematol Oncol 2016, DOI: 10.1002/hon.2338]. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.

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Section: Discussionmentioning

confidence: 99%

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy

et al. 2016

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“…Warm AIHA accounts for 60–70% of adult cases and 50% of pediatric cases [ 6 ]. In 20–25% of cases, cold agglutinins (often IgM) activate C 3 [ 7 ]. In 40% of pediatric cases, paroxysmal cold hemoglobinuria forms secondary to Donath-Landsteiner antibodies [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 40% of pediatric cases, paroxysmal cold hemoglobinuria forms secondary to Donath-Landsteiner antibodies [ 8 ]. In 6–10% of warm-type AIHA, there are no IgG antibodies [ 7 ]. The mechanism is unclear; some hypotheses include antibody-antigen complexes that later dissociate, transitory IgG or IgM levels, or complement activated by non-RBCs targeting IgG antibody that then deposits on RBCs [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 6–10% of warm-type AIHA, there are no IgG antibodies [ 7 ]. The mechanism is unclear; some hypotheses include antibody-antigen complexes that later dissociate, transitory IgG or IgM levels, or complement activated by non-RBCs targeting IgG antibody that then deposits on RBCs [ 7 ]. C 3 -only warm AIHA has a typically mild presentation.…”

Section: Discussionmentioning

confidence: 99%

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Infectious Mononucleosis Causing Acute Liver Failure and Hemolytic Anemia in a Patient with Underlying Hereditary Hemochromatosis

2020

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Infectious mononucleosis is a largely benign disease process that occurs secondary to infection with the Epstein-Barr virus. However, it can also present with more serious complications, including auto-immune hemolytic anemia and acute liver failure. Hereditary hemochromatosis is a genetic disorder that leads to organ damage via increased iron uptake and deposition. This case report describes a 25-year-old man who presented with acute liver failure and severe hemolytic anemia. Workup revealed that not only did he have a rare presentation of Epstein-Barr virus-induced acute liver failure and C3-positive IgG-negative hemolytic anemia, he also had previously undiagnosed hereditary hemochromatosis. This combined presentation of these pathologies presents a unique opportunity to study their interaction and possible synergistic pathophysiology. Furthermore, the evolving understanding of the disease mechanisms behind these disease processes is described.

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“…Eine arzneimittelinduzierte AIHA kann entweder vom Wärme-oder vom Kältetyp sein, je nach der Temperatur, bei der die Autoantikörper aktiv werden. Durch Wärmeantikörper bedingte AIHA wird in der Regel durch IgG vermittelt, das sich an den FcRezeptor von phagozytischen Zellen bindet, der Mediator kann aber in seltenen Fällen auch IgM, IgA, eine Kombination dieser 3 Antikörper oder aber C3 allein sein [6]. Die Autoantikörper werden hier bei Temperaturen ab 37 ° C aktiv [7].…”

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Autoimmunhämolytische Anämie als Komplikation der Nivolumab-Therapie

et al. 2017

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In letzter Zeit ist das Instrumentarium zur Bekämpfung verschiedener maligner Erkrankungen maßgeblich um mehrere Immuntherapeutika erweitert worden - von PD-1-Inhibitoren (Nivolumab, Pembrolizumab) über PD-L1-Inhibitoren (Atezolizumab, Avelumab) bis hin zu CTLA4-Inhibitoren (Ipiliumumab). Sie alle sind in die Behandlungsprotokolle der ersten, zweiten oder dritten Therapielinie für diese metastatischen Krebserkrankungen aufgenommen worden. Der Immun-Checkpoint-Inhibitor Nivolumab ist derzeit von der FDA in folgenden Indikationen zugelassen: bei metastasiertem malignem Melanom (Redman JM, et al.: BMC Med 2016;14:20), bei metastasiertem nichtkleinzelligem Bronchialkarzinom (Guibert N, Mazières J: Expert Opin Biol Ther 2015;15:1789-1797), bei metastasiertem Nierenzellkarzinom (Farolfi A, et al.: Expert Opin Drug Metab Toxicol 2016;12:1089-1096) sowie bei rezidivierendem oder therapierefraktärem klassischem Hodgkin-Lymphom (Villasboas JC, Ansell SM: Expert Rev Anticancer Ther 2016;16:5-12). In Anbe- tracht der bereits bestehenden und hinzukommenden Anwendungsgebiete dieser Arzneimittel ist es für Ärzte unerlässlich, sich auch gut mit ihren typischen Nebenwirkungen vertraut zu machen und aufmerksam auf andere, weniger umfassend dokumentierte Gesundheitsstörungen zu achten, die durch Anwendung dieser Arzneimittel ermittelt werden könnten. Eine definitive Assoziation zwischen autoimmunhämolytischer Anämie und dem Immun-Checkpoint-Inhibitor Nivolumab ist nicht eindeutig belegt, jedoch wurde in jüngerer Zeit von mehreren Fällen berichtet (Kong BY, et al.: Melanoma Res 2016;26:202-204; Schwab KS, et al.: Case Rep Oncol 2016;9:373-378; Tardy MP, et al.: Hematol Oncol 2016;DOI:10.1002/hon.2338). Wir berichten hier über einen Fall von steroidrefraktärer, tödlich verlaufender autoimmunhämolytischer Anämie bei einem Patienten, der wegen metastasiertem Lungenkrebs mit Nivolumab behandelt wurde. Außerdem gehen wir auch auf die anderen in der Literatur vorliegenden Fälle von autoimmunhämolytischer Anämie nach Anwendung von Nivolumab ein. Übersetzung aus Case Rep Oncol 2016;9:691-697(DOI: 10.1159/000452296)

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Warm Autoimmune Hemolytic Anemia with a Direct Antiglobulin Test Positive for C3 and Negative for IgG: A Case Study and Analytical Literature Review of Incidence and Severity

Cited by 9 publications

References 15 publications

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy

Infectious Mononucleosis Causing Acute Liver Failure and Hemolytic Anemia in a Patient with Underlying Hereditary Hemochromatosis

Autoimmunhämolytische Anämie als Komplikation der Nivolumab-Therapie

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