INVESTIGATION OF THE MECHANISM OF DRUG-INDUCED AUTOIMMUNE HEMOLYTIC ANEMIA IN CYNOMOLGUS MONKEYS ELICITED BY A REPEATED-DOSE OF A HUMANIZED MONOCLONAL ANTIBODY DRUG

2003 ◽  
Vol 28 (3) ◽  
pp. 123-138 ◽  
Author(s):  
Kazuto WATANABE ◽  
Ryosuke WATANABE ◽  
Akifumi SHIODA ◽  
Keiji MIZOGUCHI ◽  
Tetsuro SUGIMOTO ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Repeated Dose ◽  
Drug Induced ◽  
Cynomolgus Monkeys ◽  
Humanized Monoclonal Antibody ◽  
Antibody Drug

scholarly journals Murine autoimmune hemolytic anemia resulting from Fc gamma receptor- mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2960-2964 ◽  
Author(s):  
T Berney ◽  
T Shibata ◽  
R Merino ◽  
Y Chicheportiche ◽  
V Kindler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Colony Stimulating Factor ◽  
Fc Gamma Receptor ◽  
Interleukin 3 ◽  
Gamma Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor- mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM-CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia.

Immune-Mediated Hemolytic Anemia

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 48-62 ◽  
Author(s):  
Wendell F. Rosse ◽  
Peter Hillmen ◽  
Alan D. Schreiber
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Hemolytic Anemia ◽  
Complement Activation ◽  
Autoimmune Hemolytic Anemia ◽  
Clinical Manifestations ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Remarkable Effect

Abstract Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fcγ receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is outlined and the potential of therapy of these diseases by regulation of these receptors is discussed. In Section III, Dr. Wendell Rosse discusses the forms of autoimmune hemolytic anemia characterized by antibodies that react preferentially in the cold–cold agglutinin disease and paroxysmal cold hemoglobinuria (PCH). The former is due to IgM antibodies with a common but particular structure that reacts primarily with carbohydrate or carbohydrate-containing antigens, an interaction that is diminished at body temperature. PCH is a less common but probably underdiagnosed illness due to an IgG antibody reacting with a carbohydrate antigen; improved techniques for the diagnosis of PCH are described. Therapy for the two disorders differs somewhat because of the differences in isotype of the antibody. Since the hemolysis in both is primarily due to complement activation, the potential role of its control, as by the monoclonal antibody described by Dr. Hillmen, is discussed.

scholarly journals Murine autoimmune hemolytic anemia resulting from Fc gamma receptor- mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2960-2964 ◽  
Author(s):  
T Berney ◽  
T Shibata ◽  
R Merino ◽  
Y Chicheportiche ◽  
V Kindler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Colony Stimulating Factor ◽  
Fc Gamma Receptor ◽  
Interleukin 3 ◽  
Gamma Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor- mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM-CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia.

scholarly journals First Report of Eltrombopag Induced Severe Autoimmune Hemolytic Anemia in the Management of Waldenström Macroglobulinemia-associated Autoimmune Thrombocytopenia

2021 ◽  
Author(s):  
Yingying Shen ◽  
Hangping Ge ◽  
Baodong Ye ◽  
Zhiyin Zheng ◽  
Keding Shao ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Single Treatment ◽  
Autoimmune Thrombocytopenia ◽  
Drug Induced ◽  
Case Presentation ◽  
Waldenström Macroglobulinemia ◽  
First Report ◽  
Waldenstrom Macroglobulinemia ◽  
Platelet Level

Abstract Background: Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström Macroglobulinemia (WM). The cause of AIHA should be carefully distinguished during the disease management. Case Presentation: A 63-year-old female WM patient complicated with thrombocytopenia, 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 1-2×109/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, 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 alleviated within three days after eltrombopag withdrawal. Conclusion: This is the first report on eltrombopag-induced AIHA, and we should always keep in mind of the drug induced hemolysis even in disorders with autoimmune background.

scholarly journals Autoimmune Hemolytic Anemia Induced by Levofloxacin

2014 ◽  
Vol 2014 ◽  
pp. 1-2
Author(s):  
Marwan Sheikh-Taha ◽  
Pascale Frenn
Keyword(s):  
Emergency Department ◽  
Urinary Tract Infection ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Rare Condition ◽  
White Female ◽  
Coombs Test ◽  
Drug Induced ◽  
Indirect Bilirubin ◽  
Patient Reported

Drug-induced autoimmune hemolytic anemia is a rare condition. We report the case of a 32-year-old white female who presented to the emergency department with generalized fatigue, fever, and jaundice. The patient reported using levofloxacin few days prior to presentation for urinary tract infection. The patient had evidence of hemolytic anemia with a hemoglobin of 6.7 g/dL which dropped to 5 g/dL on day 2, the direct Coombs test was positive, indirect bilirubin was 5.5 mg/dL, and LDH was 1283 IU/L. Further testing ruled out autoimmune disease, lymphoma, and leukemia as etiologies for the patient’s hemolytic anemia. Levofloxacin was immediately stopped with a gradual hematologic recovery within few days.

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