scholarly journals Drug-induced immune hemolytic anemia

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 73-79 ◽  
Author(s):  
George Garratty
Keyword(s):  
Membrane Proteins ◽  
Hemolytic Anemia ◽  
Drug Induced ◽  
Serological Tests ◽  
Laboratory Findings ◽  
Rbc Membrane ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent

Abstract Drug-induced immune hemolytic anemia (DIIHA) is rare, and a specialized laboratory is often required to provide the optimal serological tests to confirm the diagnosis. The most common drugs associated with DIIHA and the hypotheses for the mechanisms thought to be involved have changed during the last few decades. The drugs most frequently associated with DIIHA at this time are cefotetan, ceftriaxone, and piperacillin. DIIHA is attributed most commonly to drug-dependent antibodies that can only be detected in the presence of drug (eg, cephalosporin antibodies). DIIHA can also be associated with drug-independent antibodies; such antibodies do not need drug to be present to obtain in vitro reactions (eg, fludarabine). In these latter cases, the drug affects the immune system, causing production of red cell (RBC) autoantibodies; the clinical and laboratory findings are identical to autoimmune hemolytic anemia (AIHA), other than the remission associated with discontinuing the drug. Some of the mechanisms involved in DIIHA are controversial. The most acceptable one involves drugs, like penicillin, that covalently bind to proteins (eg, RBC membrane proteins); RBCs become coated with drug in vivo and, a drug antibody (usually IgG) attaches to the drug-coated RBCs that are subsequently cleared by macrophages. The most controversial is the so-called immune complex mechanism, which has been revised to suggest that most drugs are capable of binding to RBC membrane proteins, but not covalently like penicillins. The combined membrane plus drug can create an immunogen; the antibodies formed can be IgM or IgG and often activate complement, leading to acute intravascular lysis and sometimes renal failure; fatalities are more common in this group. It is still unknown why and how some drugs induce RBC autoantibodies, sometimes causing AIHA.

scholarly journals On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1006-1010 ◽  
Author(s):  
A Salama ◽  
C Mueller-Eckhardt
Keyword(s):  
Specific Binding ◽  
Drug Induced ◽  
Cell Complexes ◽  
Large Panels ◽  
Plot Analysis ◽  
Number Of Patients ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Reaction Patterns

Abstract The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug- dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as “innocent bystanders,” but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug- cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.

Red Cell Antigens as Functional Molecules and Obstacles to Transfusion

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 445-462 ◽  
Author(s):  
George Garratty ◽  
Marilyn J. Telen ◽  
Lawrence D. Petz
Keyword(s):  
Hemolytic Anemia ◽  
Membrane Integrity ◽  
In Vivo Studies ◽  
Blood Group Antigens ◽  
Rbc Membrane ◽  
Pathophysiological Role ◽  
Group A ◽  
Universal Donor

Abstract Blood group antigens (BGAs) can act as functional molecules but also can evoke autoantibodies and alloantibodies, causing autoimmune hemolytic anemia, hemolytic disease of the newborn and hemolytic transfusion reactions. In Section I, Dr. Marilyn Telen discusses physiologic and pathologic functions of RBC BGA-bearing molecules. She reviews some associations of BGAs with RBC membrane integrity and hemolytic anemia; association of BGAs with enzymatic and transport functions; and adhesion molecules expressed by RBCs, especially with reference to their pathophysiological role in sickle cell disease. In Section II, Dr. Lawrence Petz discusses the problems of providing blood for patients who have RBC autoantibodies. He provides an algorithm for excluding the presence of “hidden” alloantibodies, when all units appear to be incompatible due to the autoantibody. He emphasizes that clinicians should be aware of these approaches and not accept “the least incompatible unit.” In Section III, Dr. George Garratty describes two processes, in development, that produce RBCs that result in RBCs that can be described as “universal” donor or “stealth” RBCs. The first process involves changing group A, B, or AB RBCs into group O RBCs by removing the immunospecific sugars responsible for A and B specificity by using specific enzymes. The second process involves covering all BGAs on the RBC surface using polyethylene glycol (PEG). Results of in vitro and in vivo studies on these modified RBCs are discussed.

scholarly journals Sensitivity to a Metabolite of Diclofenac as a Cause of Acute Immune Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 407-413 ◽  
Author(s):  
D. Bougie ◽  
S.T. Johnson ◽  
L.A. Weitekamp ◽  
R.H. Aster
Keyword(s):  
Hemolytic Anemia ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Proton Nuclear Magnetic Resonance ◽  
Glucuronide Conjugate ◽  
Negative Results ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Liquid Chromatographic

A 75-year-old woman taking the nonsteroidal anti-inflammatory drug diclofenac (DCF ) presented with acute Coombs-positive hemolytic anemia and subsequently developed renal failure. A drug-dependent antibody specific for red blood cells (RBCs) could not be demonstrated by in vitro testing with DCF. However, her serum was found to contain an IgM antibody that reacted strongly with RBCs in the presence of urine from any of four subjects who had ingested DCF. The active substance in urine was isolated, subjected to high-performance liquid chromatographic (HPLC) analysis, and found to be a glucuronide conjugate of a known DCF metabolite, 4′-hydroxydiclofenac (4′-OH DCF ). Negative results were obtained with four other DCF metabolites. Two 4′-OH DCF glucuronides were synthesized in vitro using a liver microsomal system. One promoted agglutination of normal RBCs by the patient's serum and was identified as the glucuronide ester of 4′-OH DCF by proton nuclear magnetic resonance (NMR) analysis. Studies with a panel of RBCs showed that the patient's antibody reacted preferentially with the e antigen of the Rh system. Acute immune hemolytic anemia in this patient appears to have been caused by sensitization to DCF modified by 4′ hydroxylation and glucuronidation. This is the first reported example of immune cytopenia caused by sensitivity to a glucuronide conjugate of a drug metabolite. Since glucuronidation is a common pathway of drug metabolism, studies of the frequency with which glucuronide derivatives of primary medications cause immune cytopenia seem warranted.

scholarly journals Pathophysiology and Diagnosis of Drug-Induced Immune Thrombocytopenia

2020 ◽  
Vol 9 (7) ◽  
pp. 2212 ◽  
Author(s):  
Caroline Vayne ◽  
Eve-Anne Guéry ◽  
Jérôme Rollin ◽  
Tatiana Baglo ◽  
Rachel Petermann ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Clinical Syndrome ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Life Threatening ◽  
Thrombotic Complications ◽  
Drug Dependent

Drug-induced immune thrombocytopenia (DITP) is a life-threatening clinical syndrome that is under-recognized and difficult to diagnose. Many drugs can cause immune-mediated thrombocytopenia, but the most commonly implicated are abciximab, carbamazepine, ceftriaxone, eptifibatide, heparin, ibuprofen, mirtazapine, oxaliplatin, penicillin, quinine, quinidine, rifampicin, suramin, tirofiban, trimethoprim-sulfamethoxazole, and vancomycin. Several different mechanisms have been identified in typical DITP, which is most commonly characterized by severe thrombocytopenia due to clearance and/or destruction of platelets sensitized by a drug-dependent antibody. Patients with typical DITP usually bleed when symptomatic, and biological confirmation of the diagnosis is often difficult because detection of drug-dependent antibodies (DDabs) in the patient’s serum or plasma is frequently not possible. This is in contrast to heparin-induced thrombocytopenia (HIT), which is a particular DITP caused in most cases by heparin-dependent antibodies specific for platelet factor 4, which can strongly activate platelets in vitro and in vivo, explaining why affected patients usually have thrombotic complications but do not bleed. In addition, laboratory tests are readily available to diagnose HIT, unlike the methods used to detect DDabs associated with other DITP that are mostly reserved for laboratories specialized in platelet immunology.

scholarly journals Sensitivity to a Metabolite of Diclofenac as a Cause of Acute Immune Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 407-413 ◽  
Author(s):  
D. Bougie ◽  
S.T. Johnson ◽  
L.A. Weitekamp ◽  
R.H. Aster
Keyword(s):  
Hemolytic Anemia ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Proton Nuclear Magnetic Resonance ◽  
Glucuronide Conjugate ◽  
Negative Results ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Liquid Chromatographic

Abstract A 75-year-old woman taking the nonsteroidal anti-inflammatory drug diclofenac (DCF ) presented with acute Coombs-positive hemolytic anemia and subsequently developed renal failure. A drug-dependent antibody specific for red blood cells (RBCs) could not be demonstrated by in vitro testing with DCF. However, her serum was found to contain an IgM antibody that reacted strongly with RBCs in the presence of urine from any of four subjects who had ingested DCF. The active substance in urine was isolated, subjected to high-performance liquid chromatographic (HPLC) analysis, and found to be a glucuronide conjugate of a known DCF metabolite, 4′-hydroxydiclofenac (4′-OH DCF ). Negative results were obtained with four other DCF metabolites. Two 4′-OH DCF glucuronides were synthesized in vitro using a liver microsomal system. One promoted agglutination of normal RBCs by the patient's serum and was identified as the glucuronide ester of 4′-OH DCF by proton nuclear magnetic resonance (NMR) analysis. Studies with a panel of RBCs showed that the patient's antibody reacted preferentially with the e antigen of the Rh system. Acute immune hemolytic anemia in this patient appears to have been caused by sensitization to DCF modified by 4′ hydroxylation and glucuronidation. This is the first reported example of immune cytopenia caused by sensitivity to a glucuronide conjugate of a drug metabolite. Since glucuronidation is a common pathway of drug metabolism, studies of the frequency with which glucuronide derivatives of primary medications cause immune cytopenia seem warranted.

scholarly journals Case Report: First Case of Cefotaxime-Sulbactam-Induced Acute Intravascular Hemolysis in a Newborn With ABO Blood Type Incompatibility by the Mechanism of Non-Immunologic Protein Adsorption

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanjun Wu ◽  
Yong Wu ◽  
Yong Yang ◽  
Baochan Chen ◽  
Jianqun Li ◽  
...  
Keyword(s):  
Protein Adsorption ◽  
Specific Binding ◽  
Blood Type ◽  
Intravascular Hemolysis ◽  
Drug Induced ◽  
First Case ◽  
Immune Hemolytic Anemia ◽  
Abo Blood Type ◽  
Drug Dependent

BackgroundABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN.Case presentationWe report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother’s blood type was O and RhD-positive, and the newborn’s blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother’s plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. In vitro experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis.ConclusionThe NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn’s plasma to the newborn’s RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.

scholarly journals Case Report: Oral Cimetidine Administration Causes Drug-Induced Immune Hemolytic Anemia by Eliciting the Production of Cimetidine-Dependent Antibodies and Drug-Independent Non-specific Antibodies

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuanjun Wu ◽  
Yong Wu ◽  
Yanli Ji ◽  
Yanhui Liu ◽  
Dongsheng Wu ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Medical Monitoring ◽  
Drug Induced ◽  
Serological Tests ◽  
Specific Antibodies ◽  
Immune Hemolytic Anemia ◽  
Antiglobulin Test ◽  
Pathogenic Antibodies ◽  
Multiple Patients ◽  
Oral Cimetidine

Previously, it was reported that multiple patients had hemolytic anemia associated with cimetidine administration, while only one patient who had received intravenous cimetidine was serologically diagnosed with drug-induced immune hemolytic anemia (DIIHA) caused by cimetidine-dependent antibodies. However, the ability of oral cimetidine intake to induce the production of antibodies has not been examined. In this study, we report a 44-year-old male patient in whom oral cimetidine administration resulted in cimetidine-dependent antibodies and drug-independent non-specific antibodies, leading to the development of DIIHA. Serological tests showed that the results of direct antiglobulin test (DAT) for anti-IgG (3+) and anti-C3d (1+) were positive. The IgM and IgG cimetidine-dependent antibodies (the highest total titer reached 4,096) were detected in the plasma incubated with O-type RBCs and 1 mg/mL cimetidine or the plasma incubated with cimetidine-coated RBCs. IgG-type drug-independent non-specific antibodies were detected in blood samples collected at days 13, 34, 41, and 82 post-drug intake. This is the first study to report that oral administration of cimetidine can elicit the production of cimetidine-dependent antibodies, leading to DIIHA, and the production of drug-independent non-specific antibodies, resulting in hemolytic anemia independent of cimetidine. Presence of pathogenic antibodies were detectable longer than 41 days. This suggests that patients with DIIHA caused by cimetidine need to be given necessary medical monitoring within 41 days after cimetidine intake.

scholarly journals On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1006-1010 ◽  
Author(s):  
A Salama ◽  
C Mueller-Eckhardt
Keyword(s):  
Specific Binding ◽  
Drug Induced ◽  
Cell Complexes ◽  
Large Panels ◽  
Plot Analysis ◽  
Number Of Patients ◽  
Immune Hemolytic Anemia ◽  
Drug Dependent ◽  
Reaction Patterns

The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug- dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as “innocent bystanders,” but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug- cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.

scholarly journals A RETROSPECTIVE STUDY OF THE TREATMENT RESULTS OF 40 DIVERSE PATIENTS OF ANEMIA

2021 ◽  
Author(s):  
George Zhu
Keyword(s):  
Complete Remission ◽  
Peer Review ◽  
Hemolytic Anemia ◽  
Iron Status ◽  
Megaloblastic Anemia ◽  
Deficiency Anemia ◽  
Drug Induced ◽  
Effective Prevention ◽  
Immune Hemolytic Anemia

Background and objective: Anemia is clinical common event. There are many types of anemias, which included stem cell problems, vitamin deficiency, chronic diseases and drug antibody -induced immune hemolytic anemia. In this study, a retrospective purpose was investigated to assess the clinical efficacy of treatment and their outcome. Methods: Total 40 patients with different types of anemias were presented in the second affiliated hospital of central south University, China and my tumor institute during 1989-2019. The therapeutically design among those patients with anemias was setted to the various regimen according to diseases diagnoses. Results and conclusion: Total 23 patients achieved cure or complete remission (CR), with the exception of refractory cancers and uremic anemia. Iron supplement was provided in 5 iron deficiency anemia. One megaloblastic anemia produced an excellent response following the supplement of vitamin B12 and folic acid. 2 aplastic anemia obtained complete remission with the integrated protocol of methyl testosterone, adenine, leucogen, and levamisol. Steroid hormone (e.g. prednisone) mixed traditional medicine were occasionally promising benefit in a nephrotic syndrome and renal insufficiency. Among 2 cases with drug-induced immune hemolytic anemia (DIIHA), laboratory studies one patient's serum contained paracetamol-dependent antibody that in the presence of paracetamol, agglutinated in-vitro with "O" red cells with or without complement. Drug antibody titer was 1:4 positive. Immune hemolysis was mediated by both the immune complex and uptake of drugs, whereas hemolysis induced by another native herb was caused by absorption of the drug only. In addition, with respect to anemia induced by malignancies, the molecular genomic regulation of retinoic acid in APL has been elucidated (see illustration in full text). Therefore, promoting effective prevention and / or early preventive treatment of anemia is our concern.                    Peer Review History: Received 5 March 2021; Revised 27 March; Accepted 23 April, Available online 15 May 2021 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.  Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Bilge Ahsen KARA,  Ankara Gazi Mustafa Kemal Hospital, Turkey, [email protected] Prof. Dr. Hassan A.H. Al-Shamahy,  Sana'a University, Yemen, [email protected] Similar Articles: THE ASSOCIATION BETWEEN LEVELS OF HEPCIDIN, IRON STATUS AND MICRO-INFLAMMATION MARKERS AMONG HAEMODIALYSIS

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