Progress in immune hemolytic anemia caused by drugs / 中国输血杂志

Drug-induced immune hemolytic anemia (DIIHA) is a rare cytopenia caused by damage to RBCs by drug-induced antibodies or non-immune protein adsorption (NIPA). The drugs associated with DIIHA and the mechanistic hypotheses that are thought to be involved have been controversial, with complex serological tests often required by specialized Immune Hematology laboratories for diagnosis. It is necessary to know the clinical manifestation and laboratory diagnosis of DIIHA in order to distinguish the immuno-hematological abnormality caused by drugs from other causes. How to improve the diagnostic ability of DIIHA and establish a scientific and reasonable idea of DIIHA serological examination is urgent to help clinical diagnosis and correct treatment.

Detection of antibiotic antibodies in 358 patients with anemia: comparative analysis of two methods / 中国输血杂志

【Objective】 To investigate the frequency of antibiotic antibodies in hospitalized patients with anemia and analyze the yieldingresults. 【Methods】 The blood samples of 358inpatients with anemia, whohad taken antibiotics for 3 days or more, were selected. The drug-coated red blood cell method and drug addition method were used for the detection of antibodies toantibiotic drug, and the relevant clinical data were consulted for comprehensive analysis of the experimental results. 【Results】 Among the 358 blood samples, antibiotic antibodies were detectedin 12 by drug-coated red blood cell method, with ayielding rate of 3.35%(12/358). 6 out of 284 samples subjected to cephalosporin antibodies testing were positive, with a positive rate at 2.11%(6/284), and6 out of 74 samples subjected to non-cephalosporins antibodies testing were positive, with a positive rate at 8.11%(6/74), showingstatistical significance between the above two positive rates(P0.05). No antibiotic antibodies were yielded in blood samples bydrug addition method. 【Conclusion】 The corresponding antibodiesagainst antibiotic could be produced insome patientsafter takingantibiotics.Therefore, enhancing the clinical attentionto antibiotic antibodies is of great significance to the effective application of clinical antibioticsand the accuracy of blood transfusion therapy.

Laboratory Workup of Drug-Induced Immune Hemolytic Anemia / 대한수혈학회지

Drug-induced immune hemolytic anemia (DIIHA) is rare condition that is often very difficult to diagnose. For proper diagnosis of DIIHA, careful interpretation of laboratory findings as well as correlation between those findings with the patient's history is important. Therefore, the role of the laboratory physician is critical. DIIHA can be diagnosed using a stepwise approach, from suspicion of hemolytic anemia in the patient to confirmation of serologic tests. Prompt diagnosis is necessary since an essential part of DIIHA treatment is to cease drug administration, and many cases of hemolysis can be improved without further intervention. Furthermore, distinction between the mechanisms of DIIHA is important, as clinical manifestation, treatment options, and prognosis of the disease can differ according to the main mechanism involved in the process of hemolysis.

A Case of Immune Hemolytic Anemia due to Autoantibodies Against C and e Antigens in a Patient with Paroxysmal Nocturnal Hemoglobinuria and Myelodysplastic Syndrome / 대한수혈학회지

Antiglobulin test-negative hemolytic anemia, thrombophilia, and marrow failure, such as aplastic anemia and myelodysplastic syndrome - refractory anemia (MDS-RA), are the primary clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH). Here, we report on a case of a 56-year-old male patient diagnosed with PNH, MDS-RA, and immune hemolytic anemia (IHA). The patient was transferred to the hospital with an impression of hemolytic anemia and pulmonary embolism. Positive results were observed on direct and indirect antiglobulin tests, and alloantibody, anti-C and anti-e, autoantibodies were identified. In addition, C and e antigens were found in Rh subgrouping. Therefore, due to the presence of autoantibodies against C and e antigens, we assumed that the cause of IHA was autoimmune reaction. Spherocytosis, increased osmotic fragility test, and positivity on direct and indirect antiglobulin tests were not considered characteristics of PNH. Therefore, without the presence of pulmonary embolism and MDS-RA, it is possible that autoimmune hemolytic anemia was considered the only reason for the hemolytic anemia, and that PNH could be overlooked. In patients with PH, use of washed RBCs during transfusion is not necessary. PNH screening test is recommended for patients who have experienced a thromboembolic event and intravascular hemolysis or MDS-RA. In order to obtain accurate information regarding the percentage of GPI-AP-deficient RBCs, flow cytometric analysis should be performed prior to transfusion.

Immune Hemolytic Anemia after ABO-mismatched Liver Transplantation: A Case Report / 대한수혈학회지

Limitations due to lack of appropriate available donors for liver transplantation necessitates the use of ABO-mismatched donors. Transplantation of ABO-mismatched solid organs is sometimes associated with the development of immune hemolytic anemia, which is caused by production of antibodies by the donor B lymphocytes in a primary or secondary immune response against the recipient's red blood cell antigens. This condition is referred to as Passenger Lymphocyte Syndrome (PLS). PLS is more frequent in heart and lung transplants than in liver and kidney transplants with incidence of PLS in liver transplantation at 30~40%. When present, PLS typically manifests 1~3 weeks after transplantation, and subsides within 3 months after symptoms are first detected. In most patients, PLS is self-limiting and exhibits mild symptoms, but in some cases PLS can be life-threatening. We report a case of immune hemolytic anemia after an ABO-mismatched liver transplantation involving a blood group O donor and a blood group A recipient, and successful treatment of the resulting PLS symptoms by transfusion of gamma-irradiated group O Red Blood Cells (RBCs) accompanied by administration of 60 mg/day of methylprednisolone for 1 week.

Discussion on etiology and pathogenesis to drug-induced immune hemolytic anemia / 国际中医中药杂志

Drug-induced immune hemolytic anemia has complicated manifestations and pathogenesis, and therefore clinicians should know its etiology and pathogenesis for safe medication. In this paper, we made a discuss on the etiology and pathogenesis of drug-induced immune hemolytic anemia from both traditional Chinese and western medicine viewpoint hoping to provide references for clinical physicians.

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

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.

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.

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.

The significance of a positive direct antiglobulin test: Comparison between the microcolumn method and conventional tube method / 대한임상병리학회지

BACKGROUND: The direct antiglobulin test(DAT) is a method detecting red cell-coated antibodies, much of which are related to immune hemolytic anemia. The microcolumn method-direct antiglobulin test(MC-DAT) is known to be more sensitive and convenient than conventional tube method-direct antiglobulin test(T-DAT). We compared the results of both DAT methods and evaluated the relationship between positive DAT result and immune hemolytic anemia. METHODS: Ninety-three subjects were classified into three groups according to clinical diagnosis, hemoglobin level, and serum IgG level; 15 healthy controls(group I), 8 patients without anemia and with total IgG greater than 1800 g/dL(group II), and 69 anemic patients with hemoglobin less than 10 g/dL(group III). DAT was performed on the EDTA-anticoagulated samples of these patients using both microcolumn method and tube method. Additional tests for hemolytic anemia were performed when either the result of MC-DAT or T-DAT was positive, and diagnosis of hemolysis was divided into three categories: hemolysis(category A), undetermined(category B), and no hemolysis(category C). RESULTS: Of total 93 samples, 18 were positive and 48 were negative with both DAT methods. Twenty-seven samples showed positive results by MC-DAT and negative by T-DAT, while none showed to be negative results by MC-DAT and positive by T-DAT. The agglutination strength of MC-DAT was stronger than that of T-DAT. Five samples which could be categorized to category A showed positive results by MC-DAT and negative by T-DAT. Two samples showing positive results with both methods but which were categorized to category C could be found in group II. CONCLUSIONS: The microcolumn method(MC-DAT) seems to be more sensitive than the tube method. However, diagnosis of immune hemolytic anemia based on the DAT result needs much caution because both methods can be influenced by high serum IgG concentration and these can show false positive results.

A Case of Immune Hemolytic Anemia after Renal Transplantation / 대한이식학회지

Several cases of immune hemolytic anemia have been reported after renal transplantation of ABO-minor-mismatch. We present a case of anti-B immune hemolytic anemia which developed on 11th day after renal transplantation. 48-year-old man, blood group Rh(+) AB, had a successful renal transplantation from his distant family, blood group Rh(+) A. He was maintained under immunosuppression with cyclosporine and prednisolone. On 11th day after renal transplantation he had a hemolytic episode. His hemoglobin dropped from 9.2 g/dl to 7.3 g/dl and corrected reticulocyte count increased to 3.7%. The peripheral blood morphology showed polychromatophilia, spherocytosis, and anisocytosis. Direct antiglobulin tests were positive with anti-IgG and anti-C3d. The antibody that caused hemolytic anemia was confirmed as anti-B IgG. The anti-B antibodies might be originated from passenger's donor B lymphocyte.

Cefuroxime Induced Immune Hemolytic Anemia / 대한임상병리학회지

Cephalosporins are commonly used antibiotics in treatment of clinical infection. They frequently cause a positive direct antiglobulin test, but rarely cause hemolysis. The authors report a case of immune hemolytic anemia due to a second-generation cephalosporin, cefuroxime, by the drug adsorption mechanism.