Drug-induced Immune Hemolytic Anemia Research Articles

A case report of severe drug-induced immune hemolytic anemia caused by piperacillin

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01–0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

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.

Tyrosine kinase inhibitor-induced immune hemolytic anemia; three different drugs in three separate cases.

Molecular multitargeted small tyrosine kinase inhibitory (TKI) agents such as axitinib, sunitinib and pazopanib are commonly used in several types of solid tumors. Anemia is not a rare effect of these drugs which may occur at all grades. However, drug-induced immune hemolytic anemia (IHA), a very rare condition is distinctive from other types of anemia with its specific mechanism and management strategy. We reported three different TKI-induced IHA cases that occurred due to axitinib, sunitinib, and pazopanib, respectively. The first two cases were diagnosed with renal cell carcinoma and the last one was diagnosed with soft tissue sarcoma. They all presented with the characteristic symptoms of anemia and hemolysis. All the cases were detected positive for the complement C3d direct antiglobulin (direct coombs) test. Discontinuation of the causative drug and 1 mg/kg/day dose of corticosteroid treatment were able to control IHA in all three cases. Excluding the other factors of IHA and an evident laboratory and clinical benefit after withholding the TKI led to the diagnosis of TKI-related IHA in each case. TKIs are relatively new in clinical practice and are being used for more indications and in more patients. To our knowledge#these three cases are unique in terms of axitinib#sunitinib#and pazopanib-related IHA.

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review

BackgroundPiperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam.Case presentationA 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped.ConclusionThis is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

Antineoplastic drug-induced immune hemolytic anemia resulting in acute kidney injury: lesson for the clinical nephrologist.

Antineoplastic drug-induced immune hemolytic anemia resulting in acute kidney injury: lesson for the clinical nephrologist.

A RARE CAUSE OF RECURRENT HAEMOLYTIC ANAEMIA: CARBOPLATIN AND PACLITAXEL-INDUCED AUTOIMMUNE HAEMOLYTIC ANAEMIA.

Drug-induced immune haemolytic anaemia (DIIHA) should be suspected in patients with abrupt immune haemolytic anaemia with a temporal relationship between drug exposure and symptom onset.The main management of DIIHA consists of urgent discontinuation of the suspected drug and supportive treatment with close monitoring, resulting in a favourable outcome in most cases; the role of corticosteroids in DIIHA remains unclear.Haeme pigment-induced acute kidney injury is induced by intravascular haemolysis where urinalysis reveals elevated haemoglobin.

Ceftazidime-induced immune hemolytic anemia: a case report

Drug-induced immune hemolytic anemia (DIIHA) is considered a rare condition. Nonsteroidal anti-inflammatory drugs and antineoplastic drugs are the main causes of DIIHA. An 86-year-old male patient with pulmonary infection was admitted to the 960^th Hospital of the PLA Joint Logistics Support Force. The patient was treated with ceftazidime in addition to supportive treatment. A history of antibiotics intake and clinical and laboratory hemolysis features were considered to be key bases for DIIHA diagnosis. Clinicians need to be aware of and accurately diagnose this rare complication caused by commonly prescribed drugs to stop the use of causative drugs in time, and therefore, to prevent serious and sometimes fatal consequences.

A hemolysis verified to be induced by anti-meropenem

Incompatibility of blood groups or unexpected antibodies are primary considerations when acute hemolysis occurs during or after transfusion. However, less attention is paid to drug-induced immune hemolytic anemia (DIIHA), which is a rare but potentially life-threatening autoimmune disease. We present the case of a 34-year-old woman (group A, RhD+) who was treated with multiple antibiotics after meningioma resection. As her hemoglobin (Hb) decreased significantly from 109 g/L to 52 g/L without obvious bleeding, a blood transfusion was conducted soon after the medication, during which acute hemolysis occurred. An unexpected antibody, anti-M (MNS blood group system), was identified in the patient. It was confirmed that both the recipient and donor were group A, M antigen negative (M−) with CCDee phenotype, and no agglutination reactivity was observed in major crossmatch by testing the specimens before and after transfusion. Meanwhile, the results of the direct antiglobulin test (DAT) changed from negative to positive. Anti-meropenem, a drug-dependent antibody of meropenem, was detected, and hemolysis resolved after cessation. Anti-meropenem may mainly act through an "immune complex-type" reaction that induces intravascular hemolysis. Notably, the peculiarity of this case was dependent on the occurrence time of the acute hemolysis. Hence, it is necessary to raise awareness of DIIHA in clinical antibiotic treatments.

Acute Hemolytic Anemia Following Semaglutide Injection: A Case Report

Background: Drug-induced immune hemolytic anemia is a serious adverse reaction that may result from drug administration, especially in cases of glucose-6-phospate dehydrogenase (G6PD) deficiency. Objective: To report a case of acute hemolytic anemia in a 30-year-old Saudi male after receiving Semaglutide injection. Case Report: A 30-year-old Saudi male with G6PD deficiency presented to the Emergency Department of Aseer Central Hospital, Abha City, Saudi Arabia with acute onset of yellow discoloration of the eyes, palpitation, mild backache, fatigue, and dark urine. The symptoms started one day after receiving the second dose of Semaglutide injection. He looked pale and the sclera were slightly icteric. Laboratory investigations showed high serum levels of liver enzymes and the total bilirubin. The RBCs count as well as the hemoglobin and the hematocrit were low, while reticulocyte count was high. The diagnosis was acute hemolytic anemia, most probably triggered by a recent Semaglutide injection. Following the discontinuation of Semaglutide, his clinical condition improved. Conclusions: G6PD deficiency should be considered in all clinical settings, and the hemolytic conditions that can possibly be precipitated by drugs not well known to cause hemolysis. Screening of newborn infants to early detect G6PD deficiency early is highly recommended, especially in those with positive family history of G6PD. Key Words: Semaglutide, Hemolytic anemia, G6PD deficiency, Case report.

Investigation of anemia of unknown origin

Abstract One of the most difficult concepts to explain when training immunohematology staff involves the investigation of hemolytic anemias. In the transfusion service and in the immunohematology reference laboratory setting, rapid and efficient investigation can be extremely important for patients with critical anemia requiring transfusion. The flow charts presented here provide possible patient scenarios and a logical sequence for initial and subsequent serologic testing for investigation. A clinical assessment of anemia of unknown origin or the finding of an unresolved positive antibody screen in pre-transfusion patient testing begins the investigational flow process. The testing sequence is predicated on the fact that performing a direct antiglobulin test (DAT) on all patients has a low predictive value and should be reserved for patients with unexplained anemia. The process begins with assessing the results of DATs with anti-IgG and anti-C3. Subsequent charts A, B, and C aid in investigating these results. Flow Chart A is for the investigation of warm or cold autoantibody, Chart B is for the investigation of cold-agglutinin or drug-induced immune hemolytic anemia, and Chart C is for the investigation of autoantibody in the transfused patient. While the most common approaches to the initial and subsequent test results are in these flow charts, the charts are not inclusive of all possible diagnoses or presentations. These flow charts are meant to be a guide to assist the laboratory in developing a standard approach to efficient investigation and resolution in patients with unexplained anemia.

Investigation of anemia ofunknownorigin.

One of the most difficult concepts to explain when training immunohematology staff involves the investigation of hemolytic anemias. In the transfusion service and in the immunohematology reference laboratory setting, rapid and efficient investigation can be extremely important for patients with critical anemia requiring transfusion. The flow charts presented here provide possible patient scenarios and a logical sequence for initial and subsequent serologic testing for investigation. A clinical assessment of anemia of unknown origin or the finding of an unresolved positive antibody screen in pre-transfusion patient testing begins the investigational flow process. The testing sequence is predicated on the fact that performing a direct antiglobulin test (DAT) on all patients has a low predictive value and should be reserved for patients with unexplained anemia. The process begins with assessing the results of DATs with anti-IgG and anti-C3. Subsequent charts A, B, and C aid in investigating these results. Flow Chart A is for the investigation of warm or cold autoantibody, Chart B is for the investigation of cold-agglutinin or drug-induced immune hemolytic anemia, and Chart C is for the investigation of autoantibody in the transfused patient. While the most common approaches to the initial and subsequent test results are in these flow charts, the charts are not inclusive of all possible diagnoses or presentations. These flow charts are meant to be a guide to assist the laboratory in developing a standard approach to efficient investigation and resolution in patients with unexplained anemia.

A Rare Case of Hydrochlorothiazide-Induced Hemolytic Anemia

Drug-induced immune hemolytic anemia is an exceedingly rare adverse drug event. Thiazide diuretics, commonly used in the treatment of primary hypertension, have been associated with this complication. In this case report, we present a 77-year-old male who developed acute hemolytic anemia two days after starting hydrochlorothiazide in the treatment of high blood pressure.

A RETROSPECTIVE STUDY OF THE TREATMENT RESULTS OF 40 DIVERSE PATIENTS OF 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, ahsndkyc@gmail.com Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, shmahe@yemen.net.ye Similar Articles: THE ASSOCIATION BETWEEN LEVELS OF HEPCIDIN, IRON STATUS AND MICRO-INFLAMMATION MARKERS AMONG HAEMODIALYSIS

Serologic characteristics of oxaliplatin antibodies in 15 patients with drug-induced immune hemolytic anemia.

Oxaliplatin, a third-generation platinum derivative is commonly used in combination treatment of metastatic colorectal cancer. Since 2008, it is the second most common cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our laboratory. Samples from fifteen patients including nine (60%) with intravascular hemolysis, suspected of having DIIHA were studied for the presence of anti-oxaliplatin. Direct antiglobulin tests (DATs) and tests with oxaliplatin-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs in the presence of oxaliplatin were performed. A pool of normal AB sera with no unexpected antibodies was used as a control for nonimmunologic protein adsorption (NIPA). Eleven (73%) of the fifteen patients had antibodies to oxaliplatin that reacted with drug-treated RBCs and untreated RBCs in the presence of drug by tube and/or gel method. Lower-titer reactivity (<20) obtained with four patients' sera and the corresponding pooled normal sera was most likely due to NIPA. Eighty seven percent (13/15) of the patients had positive DAT either with anti-IgG only (33%), IgG + C3d (40%), or C3d only (13%). Two patients had a negative DAT. No directly agglutinating antibody was observed with the pools of normal donor's sera in the presence of oxaliplatin. Anti-oxaliplatin can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and anti-oxaliplatin can be detected in the patient's serum. RBC-bound albumin detection with anti-human albumin needs to be performed to confirm NIPA which could have contributed to the patient's hemolytic anemia.

Drug-Induced Immune Hemolytic Anemia Caused by Postoperative Cefotetan Administration.

Drug-Induced Immune Hemolytic Anemia Caused by Postoperative Cefotetan Administration.

Early-onset antibiotic-induced autoimmune hemolytic anemia

Drug-induced immune hemolytic anemia (DIIHA) is a rare adverse reaction that causes secondary autoimmune hemolytic anemia in susceptible patients. Drug-induced antibodies and nonimmunological protein absorption are the known mechanisms associated with DIIHA. The two most common reported antibiotics to cause drug dependent antibodies are cephalosporin and penicillin. The author reports two rare cases of DIIHA. The first case is a middle-aged woman clinically diagnosed with community-acquired pneumonia, which develops hemolytic anemia secondary to ceftriaxone. The second case is an elderly gentleman who developed DIIHA secondary to piperacillin–tazobactam that started managing gastrostomy site infection. Both patients had hypoxemia and shortness of breath secondary to drop in hemoglobin, but the outcome was uneventful. Antibiotic-induced hemolytic anemia can develop as early as 2 days after starting the antibiotic. Therefore, early diagnosis and discontinuation of the offending agent can prevent poor prognosis.

No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials.

PurposeDrug-induced immune hemolytic anemia (DIIHA) is a rare but serious adverse event associated with a number of drugs, including second- and third-generation cephalosporins. A positive direct antiglobulin test (DAT) is a reliable finding in DIIHA, but positive results without evidence of hemolysis can occur, particularly in hospitalized patients. There have been no reports of hemolytic anemia in four previous Phase 3 trials or from post-marketing surveillance of the advanced-generation, broad-spectrum cephalosporin, ceftobiprole. The aim of this analysis was to review the incidence of positive DAT results and any evidence of hemolytic anemia from three recent Phase 3 trials of ceftobiprole.Patients and MethodsPatients were enrolled in three Phase 3 randomized controlled trials: 94 pediatric patients with pneumonia received ceftobiprole in the BPR-PIP-002 trial; 335 adults with acute bacterial skin and skin structure infections received ceftobiprole in the TARGET trial; and 201 adults with Staphylococcus aureus bacteremia have been randomized 1:1 to ceftobiprole or daptomycin ± aztreonam in the ongoing ERADICATE trial. In all three trials, DAT results were obtained at baseline, and follow-up tests were performed either at the test of cure (TOC) visit (BPR-PIP-002), end-of-treatment (EOT) visit (TARGET), or both EOT and post-treatment Day 70 visits (ERADICATE).ResultsIn the BPR-PIP-002 trial, five patients (all ceftobiprole treated) had a documented negative DAT result at baseline followed by a positive result at the TOC visit. One patient in the ongoing, blinded ERADICATE trial had a positive DAT result at both baseline and EOT. Results from other laboratory investigations showed no evidence of hemolytic anemia in these patients. No positive DAT results were reported in the TARGET trial.ConclusionNo evidence of hemolytic anemia associated with ceftobiprole was observed in either adults or children across several indications in this analysis of three large Phase 3 trials.

Drug-induced immune hemolytic anemia investigation: Comparison between tube test and microcolumn agglutination (gel test) for the detection of drug-dependent antibodies in the presence of soluble drug

Testing for drug-dependent antibodies is traditionally performed with the tube method either with drug-treated red blood cells or with untreated red blood cells in the presence of soluble drug. Gel microcolumn agglutination method was compared to tube testing for the demonstration of drug-dependent antibodies in the presence of soluble drug. Patient's samples were tested in parallel by tube and gel microcolumn agglutination method with untreated and/or enzyme-treated red blood cells in the presence of soluble drug. Twenty six different patient's samples were studied and thirty nine tests performed to investigate antibodies directed against fifteen different drugs. There was a good correlation between the results obtained by tube and gel method in terms of analytical sensitivity and specificity. Reactions appeared to be stronger with the gel test than seen with the conventional tube method for most of the drug antibodies investigated. Enzyme-treated cells should be used in addition to untreated cells to improve the sensitivity of the method for detecting drug-dependent antibodies especially those directed against drugs that do not bind firmly to red blood cells. Gel method appeared to be sensitive, reliable, reproducible, and comparable to the conventional tube method for the detection of all the drug-dependent antibodies investigated in this study. Further studies need to be performed to evaluate gel testing for the detection of drug-dependent antibodies that only react with drug-treated red blood cells.