Case Of Immune Hemolytic Anemia Research Articles

Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study

AbstractMore than 130 drugs have been suspected to induce immune hemolytic anemia. Comparative studies measuring the risk of drug-induced immune hemolytic anemia (DIIHA) are lacking. We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a nationwide comparative study. The new signals were identified using a disproportionality study (case/noncase design) in the World Pharmacovigilance Database, Vigibase, among the cases of adverse drug reactions reported up to February 2020 (>20 million). We then conducted a comparative study in the French National health database that links sociodemographic, out-of-hospital, and hospital data for the entire population (67 million individuals). Associations between exposure to drugs (those already reported as DIIHA, plus new signals identified in Vigibase) and incident cases of immune hemolytic anemia (D59.0 and D59.1 diagnosis codes of the International Classification of Diseases, version 10) from 2012 to 2018 were assessed with case-control and case-crossover designs. In Vigibase, 3371 cases of DIIHA were recorded. Fifty-nine new signals were identified resulting in a final list of 112 drugs marketed in France and measurable in the nationwide cohort (n = 4746 patients with incident immune hemolytic anemia included in the case-control analysis matched with 22 447 controls from the general population). We identified an association between immune hemolytic anemia occurrence and some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine, and iomeprol.

Utility of mean sphered cell volume and mean reticulocyte volume for the diagnosis of hereditary spherocytosis

ABSTRACTIntroduction: Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a positive laboratory test which is usually the osmotic fragility test (OFT). We conducted a study to assess the utility of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume (MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these are helpful in distinguishing cases of HS from immune hemolytic anemia.Methods: A total of 102 patients suspected to have HS were enrolled. In addition 10 cases of immune hemolytic anemia (IHA) were included in the study and performance of the above screening tests was evaluated. The diagnosis of HS was based on incubated OFT, eosin 5′-maleimide (EMA) dye binding test, and flowcytometric OFT.Results: A total of 29 patients were diagnosed as having HS. The sensitivity and specificity for diagnosis HS by MCHC > 35 g/dL was 44.82%, and ΔMCV−MSCV > 10 fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS. Using an algorithm of ΔMCV−MSCV > 10 fL and ΔMRV−MSCV < 25, for the differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%.

Bendamustine-induced immune hemolytic anemia in a chronic lymphocytic leukemia patient: A case report and review of the literature

Bendamustine is an alkylating agent approved for the treatment of chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. There are scant reports on bendamustine-induced immune hemolytic anemia occurring mainly in CLL patients. We report a case of immune hemolytic anemia that developed after exposure to bendamustine in a 70-year-old female with CLL who was previously exposed to fludarabine. Previous exposure to fludarabine is a common finding in the majority of reported cases of bendamustine drug-induced immune hemolytic anemia (DIIHA), including our case. Bendamustine should be suspected as the cause of any hemolytic anemia that develops while on this drug, especially in CLL patients treated previously with fludarabine.

Clinical study on immune neutropenia

Objective To explore the diagnosis and of immune neutopenia.Methods Clinical data of 150 patients with immune neutropenia were collected and analyzed.Results Of 150 patients with immune neutropenia,35 cases went male(23.3％),115 cases were female(76.7％),and male to female ratio was 1 ∶ 3.3.Based on the difference produced way of granulocytes associated antibody,all patients could be divided into alloimmune neonatal neutropenia 9 cases (6.0％),drug-induced immune neutropenia 28 cases (18.7 ％),primary autoimmune neutropenia 22 cases(14.6％),and secondary autoimmune neutropenia 91 cases (60.7％).Secondary autoimmune neutropenia included 39 cases of systemic lupus erythematous,21 cases of rheumatoid arthritis,2 cases of immune hemolytic anemia accompany with neutropenia,6 cases of immune thrombocytopenia accompany with neutropenia,3 cases of autoimmune hepatitis,16 cases of autoimmune thyroiditis,and 4 cases of Sjogren's syndrome.Conclusion The majority of primary immune neutropenia are female,which is usually secondary to autoimmune diseases.The diagnosis of primary immune neutropenia is very complicated,which requires a long period of clinical observation and follow-up.The majority of granulocytes associated antibody is IgG in the autoimmune neutropenia patients.Yet sometimes two or three kinds of antibodies were increased as well. Key words: Neutropenia; Antibodies ,antineutrophil cytoplasmic

A Case of Immune Hemolytic Anemia Induced by Ceftizoxime and Cefobactam (Sulbactam/Cefoperazone)

Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.

Allergic reaction to chlorambucil in chronic lymphocytic leukemia presenting with fever and lymphadenopathy

Chronic lymphocytic leukemia (CLL) is commonly treated with the alkylating agent chlorambucil. Allergic reactions to this chemotherapy are rare. Previous reports include urticaria, angioedema, rashes, toxic epidermal necrolysis, drug fever and one case of immune hemolytic anemia. We report 2 cases that had the identical symptoms of acute onset of high fever and progressive lymphadenopathy. These symptoms disappeared with conservative management. Neither of the patients were treated for infection or disease progression. When the patients were rechallenged with chlorambucil, identical reactions recurred. There was no cross-reactivity with the alkylating agent cyclophosphamide or other types of chemotherapy. This type of reaction to chlorambucil has not been described previously. It is important to recognize this as an allergic reaction. These reactions could be confused with the onset of infection, progression of disease or even a Richter's transformation.

Oxaliplatin‐induced immune pancytopenia

Oxaliplatin, a third-generation platinum compound, has been implicated in isolated cases of immune hemolytic anemia and/or immune thrombocytopenia. The first case of severe immune pancytopenia related to oxaliplatin is described. A 79-year-old woman with colorectal cancer was initially treated with 5-fluorouracil and she later received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th cycles of chemotherapy she developed thrombocytopenia, hemolysis, and neutropenia. No problems occurred during the 16th cycle without oxaliplatin. Serologic testing including detection of drug-dependent antibodies and autoantibodies was performed with standard techniques. Serologic findings included a positive immunoglobulin G direct antiglobulin test; nonreactive red blood cell (RBC) eluates; platelet (PLT)-bound antibodies to glycophorin (GP) IIb-IIIa, GPIb-IX, and GPIa-IIa; and oxaliplatin-dependent antibodies to PLTs, RBCs, and neutrophils. Oxaliplatin may lead to the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune cytopenias should always be considered in patients treated with oxaliplatin.

Ceftriaxone Induced Immune Hemolytic Anemia: Detection of Drug-dependent Antibody by Ex-vivo Antigen in Urine

There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone.

First two cases of immune hemolytic anemia associated with ceftizoxime

Second- and third-generation cephalosporins have been associated with immune-mediated hemolytic reactions. This report discusses two patients who developed clinically significant extravascular hemolysis while receiving the third-generation cephalosporin ceftizoxime (Ceftizox). This is believed to be the first time hemolysis has been described in patients receiving this drug. Immunologic workup of drug-dependent antibodies was performed on blood samples using drug-coated and immune complex methodologies. Antibody classes and titers were analyzed. Both the patients' sera contained anti-ceftizoxime that reacted with red cells only when ceftizoxime was added to the sera ("immune complex" method). The patients recovered without complications following discontinuation of the drug. Each patient had IgM and IgG drug-dependent antibodies. The drug-induced antibodies from each patient cross-reacted with cefotaxime, which is structurally similar to ceftizoxime, but cross-reacted either weakly or not at all with ceftriaxone, which has a more complex side chain. This report describes the first cases of immune hemolytic anemia associated with ceftizoxime. In drug-induced hemolytic reactions, prompt recognition and discontinuation of the drug may be important factors in reducing the chance of serious sequelae.

A Rapidly Fatal Case of Immune Haemolytic Anaemia due to Cefotetan

A Rapidly Fatal Case of Immune Haemolytic Anaemia due to Cefotetan

A Rapidly Fatal Case of Immune Haemolytic Anaemia due to Cefotetan

A Rapidly Fatal Case of Immune Haemolytic Anaemia due to Cefotetan

A fatal case of ceftriaxone (Rocephin)‐induced hemolytic anemia associated with intravascular immune hemolysis

Fatal hemolytic anemia developed in a 52-year-old woman who was treated with a cephalosporin, ceftriaxone. The patient's red cells (RBCs) were coated with C3, but no RBC-bound IgG, IgA, or IgM was detected. Her serum contained an antibody that did not react with cephalosporin-coated RBCs but reacted strongly with RBCs in vitro when her serum was added to drug and RBCs. This is the first case of immune hemolytic anemia associated with ceftriaxone, the first case of fatal cephalosporin-induced hemolytic anemia, and the second case in which a cephalosporin antibody showed in vitro and in vivo characteristics usually thought to be associated with the so-called immune complex mechanism.

Immune hemolytic anemia associated with tolmetin and suprofen

This article reports the first case of immune hemolytic anemia possibly associated with the ingestion of suprofen. The patient suffered from massive hemoglobinuria and acute renal failure. Serologic studies of the patient's serum revealed suprofen-dependent red cell antibodies. However, tolmetin-dependent antibodies were also found in the serum, showing the same properties as the suprofen antibodies and an even higher titer. The patient not only had drug-dependent antibodies in the serum, but also had developed autoantibodies, a phenomenon that has been described for several other drugs. The working mechanism by which suprofen and tolmetin caused immune hemolysis had properties of both the immune complex model and the induction of autoimmunity. Although it was unclear whether the immune hemolytic anemia was the result of suprofen, tolmetin, or cross-reacting antibodies, we feel that suprofen should be added to the list of nonsteroidal anti-inflammatory drugs associated with a positive direct antiglobulin test.

Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation

Six cases of immune hemolytic anemia attributed to donor-derived red cell antibodies after allogeneic bone marrow transplantation (BMT) are reported. In 2/6 cases, severe intravascular hemolysis was seen, 6/6 required increased red cell transfusion, and 1/6 was treated by plasma exchange. All recipients were receiving cyclosporine to prevent graft-v- host disease. Investigations showed that in each case, the donor lacked ABO or Rho(D) red cell antigens present in the recipient. The direct antiglobulin test was positive in 6/6. Relevant serum antibody (anti-A, four cases; anti-B, one case; anti-D, one case) was first detected one to three weeks after BMT. Eluates made from recipient red cells showed the same specificity as serum antibody. Maximum hemolysis occurred nine to 16 days after BMT, suggesting that active production of antibody by “passenger” donor lymphocytes was the likely mechanism of hemolysis, rather than passive transfer of antibody in the marrow infusion. Retrospective analysis of 21 consecutive cyclosporine-treated BMT patients receiving marrow lacking ABO or D antigens present in the recipient showed that (1) 15/18 patients tested had red cell antibody production against recipient red cell antigens; (2) despite the frequent presence of antibody specific for recipient red cell antigens, only 3/21 patients developed clinically significant hemolysis; (3) clinical hemolysis could not be predicted by donor or recipient red cell antibody titers. We conclude that although red cell antibody against recipient antigens is frequently produced after minor ABO and D mismatched BMT in cyclosporine-treated recipients, only 10% to 15% of cases develop clinically significant immune hemolysis. The data presented show that the most likely source of antibody is “passenger” donor lymphoid cells.

Donor-Derived Red Blood Cell Antibodies and Immune Hemolysis After Allogeneic Bone Marrow Transplantation

Six cases of immune hemolytic anemia attributed to donor-derived red cell antibodies after allogeneic bone marrow transplantation (BMT) are reported. In 2/6 cases, severe intravascular hemolysis was seen, 6/6 required increased red cell transfusion, and 1/6 was treated by plasma exchange. All recipients were receiving cyclosporine to prevent graft-v-host disease. Investigations showed that in each case, the donor lacked ABO or Rho(D) red cell antigens present in the recipient. The direct antiglobulin test was positive in 6/6. Relevant serum antibody (anti-A, four cases; anti-B, one case; anti-D, one case) was first detected one to three weeks after BMT. Eluates made from recipient red cells showed the same specificity as serum antibody. Maximum hemolysis occurred nine to 16 days after BMT, suggesting that active production of antibody by "passenger" donor lymphocytes was the likely mechanism of hemolysis, rather than passive transfer of antibody in the marrow infusion. Retrospective analysis of 21 consecutive cyclosporine-treated BMT patients receiving marrow lacking ABO or D antigens present in the recipient showed that (1) 15/18 patients tested had red cell antibody production against recipient red cell antigens; (2) despite the frequent presence of antibody specific for recipient red cell antigens, only 3/21 patients developed clinically significant hemolysis; (3) clinical hemolysis could not be predicted by donor or recipient red cell antibody titers. We conclude that although red cell antibody against recipient antigens is frequently produced after minor ABO and D mismatched BMT in cyclosporine-treated recipients, only 10% to 15% of cases develop clinically significant immune hemolysis. The data presented show that the most likely source of antibody is "passenger" donor lymphoid cells.

Detection of IgG sensitization of red cells with 125I staphylococcal protein A.

Most cases of immune hemolytic anemia are associated with a positive direct antiglobulin test. However, in some cases, the antiglobulin test is not sensitive enough to detect low levels of red-cell bound antibodies. This report describes a method using radiolabelled purified staphylococcal protein A which is capable of detecting IgG sensitization of red cells beyond the threshold of serologic techniques. It is less cumbersome than previously described methods and does not require antibody purification procedures. Its effectiveness was demonstrated for the detection of red-cell alloantibodies and in evaluation of patients with acquired hemolytic anemias associated with a negative direct antiglobulin test.

Development of immune haemolytic anaemia and thrombocytopenia in a chronic biologic false-positive reactor for syphilis.

Report of a case of immune haemolytic anaemia and thrombocytopenia antedated by 19 years with biologic false positive serological reactions for syphilis and initially associated with an aplastic crisis. The erythrocytes were heavily sensitized with complement and weakly with γG globulin. In spite of elevated cold agglutinins, the patient had not experienced Raynaud's phenomenon and there was no abnormal cold haemolysis. Ultracentrifugation studies revealed a quality change in the Wassermann antibodies that roughly parallelled the development of the haemolytic disease.