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.
Anemia, Hemolytic* ; Diagnosis ; Hemolysis ; Humans ; Prognosis ; Serologic Tests

BACKGROUND: Hepatitis B virus DNA quantification is essential for managing chronic hepatitis B (CHB). We compared the performance of artus HBV QS-RGQ (QIAGEN GmbH, Germany) and CAP/CTM v2.0 HBV assays (Roche Molecular Diagnostics, USA) in CHB patients. METHODS: A comparative evaluation between two assays was performed with 508 clinical serum samples. Precision, linearity, and the limit of detection (LOD) of QS-RGQ assay was evaluated by using the WHO standard 97/750 and clinical samples. RESULTS: Detection rates and viral loads as determined QS-RGQ assay were significantly lower than those from the CAP/CTM v2.0 assay (52.8% vs 60.6%; 3.55±1.77 IU/mL vs 4.18±1.89 IU/mL, P<0.0001). The kappa coefficient between qualitative results was 0.79 (95% confidence interval, 0.74 to 0.85). Bland-Altman plot found a mean difference of (QS-RGQ − CAP/CTM v2.0)=−0.63 log₁₀ IU/mL (95% limit of agreement, −1.48 to 0.22). Repeatability and total imprecision (% CV) of the QS-RGQ assay were 1.0% and 1.1% at 2,000 IU/mL, and 0.7% and 1.4% at 20,000 IU/mL, respectively. Linearity of this assay ranged from 31.6 to 1.0±10⁷ IU/mL, and the LOD was 2.95 IU/mL. CONCLUSIONS: The artus HBV QS-RGQ assay showed good performance but significantly decreased detection rate and viral load compared with CAP/CTM v2.0 assays. This assay recommends using plasma; however, we used stored serum because of the retrospective study design. Usually HBV DNA quantification is performed in plasma or serum, but sample type and clinical relevance of quantitative values should be considered when determining the clinical application of this reagent.
DNA ; DNA, Viral* ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Limit of Detection ; Pathology, Molecular ; Plasma ; Retrospective Studies ; Viral Load

Transfusion-associated circulatory overload (TACO) is recently becoming more important than transfusion-related acute lung injury (TRALI) in terms of the number of patients with definite diagnosis as well as its prognosis. In order to diagnose TACO, it is helpful to recognize early the symptoms suspicious of transfusion reaction through electronic medical record system and computer network, and this will be of help for obtaining samples for brain natriuretic peptide (BNP) measurement before and after the onset of transfusion reaction. We report a case in which a transfusion reaction was diagnosed as TACO. A 62-year-old woman was admitted to the emergency room due to bleeding tendency. Two fresh frozen plasma units and one unit of leukocyte-reduced red blood cells were transfused. Blood pressure increased during transfusion, and the chest X-ray showed findings suggestive of newly developed pulmonary edema. N-terminal prohormone of BNP (NT-proBNP) test was carried out using the specimens in refrigerated storage. Compared with the NT-proBNP level measured 12 hours before the transfusion, that measured 6 hours after the transfusion was markedly increased (>48 fold of pre-transfusion level). As a result, this case was diagnosed with TACO.
Acute Lung Injury ; Blood Pressure ; Diagnosis ; Electronic Health Records ; Emergency Service, Hospital ; Erythrocytes ; Female ; Hemorrhage ; Humans ; Middle Aged ; Natriuretic Peptide, Brain ; Plasma ; Prognosis ; Pulmonary Edema ; Thorax ; Transfusion Reaction

In Korea, demand for autologous serum eye drops (ASEs) is increasing for treatment of severe dry eye diseases. However, since the MFDS (Ministry of Food and Drug Safety) does not have guidelines for use of ASEs, they are manufactured according to their own protocols by each medical institution. ASEs should be taken with caution to avoid contamination during the manufacturing process since blood must be used as a raw material and must be prepared in an open space. In this paper, we briefly review reports on ASEs and share our experience with the introduction of ASE manufacturing protocols at Severance hospital.
Eye Diseases ; Korea ; Ophthalmic Solutions*

No abstract available.
Aged, 80 and over ; Ascorbate Oxidase/*metabolism ; Ascorbic Acid/administration & dosage/blood/*chemistry ; Breast Neoplasms/pathology ; Cholesterol/*blood ; *Colorimetry ; Enzyme Assays ; Female ; Humans ; Injections, Intravenous ; Intestine, Small/surgery ; Kidney/physiopathology ; Male ; Middle Aged ; Palliative Care ; Recurrence

Anti-f(ce) is a rare unexpected antibody against the ce(f) antigen. The aim of this study is to report a second case of anti-f(ce) identified in a patient. A 66-year-old-male with pancreatic cancer received percutaneous transhepatic biliary drainage. During pretransfusion tests, anti-f(ce) was identified. He had a history of multiple transfusions and was transfused with 2 units of antiglobulin crossmatch compatible RBCs without any adverse reactions. To confirm that the antibody was specific for ce(f) antigen, we crossmatched the patient's serum with RhD-positive red cells of Rh phenotype DcE, DCcEe, DCce, and DCe; all results were negative. Conversely, a crossmatch with RhD-negative red cells of Rh phenotype ce, Cce, and cEe, showed positive results for Rh phenotype ce and cEe red cells. Among the four reports that confirmed anti-e, we discovered the possibility of co-existence of anti-C or misidentification of anti-Ce as anti-e. Therefore, when antibodies against Rh antigens are identified, the possibility of co-existence of antibodies against compound antigens should be considered. Using unexpected antibody identification panel that ce(f) antigen positive red cells are marked is recommended for sensitive detection of anti-f(ce).
Antibodies ; Drainage ; Humans ; Pancreatic Neoplasms* ; Phenotype

Herein, we report a patient showing panagglutination in the unexpected antibody identification test after the administration of daratumumab. The patient was a 66-year-old woman who had undergone multiple cycles of chemotherapy and autologous peripheral blood stem cell transplantation for treating multiple myeloma; however, despite treatment, she had relapsed. Therefore, daratumumab, on clinical trials in Korea, started to be administered. After administration of daratumumab, the result of antibody screening test was positive, on the contrary to the result prior to the administration. Moreover, all positive reactions were shown in the antibody identification to the panel cells. After destroying CD38 antigens on the surface of RBCs using DTT, negative results were obtained. Daratumumab—a novel therapeutic human CD38 monoclonal antibody that can be used as targeted immunotherapy—is an FDA-approved drug for treating multiple myeloma. Because CD38 is expressed not only on myeloma cells, but also on red blood cells (RBCs), the use of daratumumab might lead to RBC agglutinations, and thereby resulting in false-positive results on the pre-transfusion tests. Therefore, caution is needed in case of a patient receiving daratumumab. Furthermore, additional test using DTT is required, especially when panagglutination was shown in the antibody identification test, as in this case.
Aged ; Antigens, CD38 ; Drug Therapy ; Erythrocytes ; Female ; Humans ; Korea ; Mass Screening ; Multiple Myeloma* ; Peripheral Blood Stem Cell Transplantation

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a condition in which immune hemolytic anemia occurs in fetuses or newborns as a result of maternal alloimunized antibodies transfer. Antibody elution test and direct antiglobulin test (DAT) can be performed to diagnose HDFN; maternal originated antibodies cannot be confirmed if DAT is utilized alone. In this study, we analyzed the clinical significance of implementing concurrent DAT and antibody elution test in diagnosing HDFN. METHODS: We retrospectively analyzed the DATs and antibody elution tests that were simultaneously conducted in a period of 11 years, between 2005 and 2015, in newborns that received hemoglobin, reticulocyte, and total bilirubin tests. According to the results of these tests, the number of newborns diagnosed with HDFN was measured. Furthermore, the sensitivity and specificity of DAT and antibody elution test were compared. RESULTS: Among 325 newborns, the results of DATs and antibody elution tests were both negative in 208 (64.0%), negative and positive, respectively, in 80 (24.6%), positive and negative in 10 (3.1%), both positive in 27 (8.3%). When this was compared to the clinical diagnosis of HDFN, more sensitive and specific diagnoses were possible when implementing DAT and antibody elution test together (sensitivity of 76.9% for antibody elution test and specificity of 90.3% for DAT). Twenty-six (8.0%) newborns suspected for HDFN showed clinically significant hemolytic anemia. CONCLUSION: It is necessary to conduct both DAT and antibody elution test when HDFN is suspected. The severity of hemolysis in HDFN can be indirectly anticipated using an antibody elution test confirming maternal originated alloantibodies.
Anemia, Hemolytic ; Antibodies ; Bilirubin ; Coombs Test* ; Diagnosis ; Fetus* ; Hemolysis ; Humans ; Infant, Newborn* ; Isoantibodies ; Reticulocytes ; Retrospective Studies ; Sensitivity and Specificity

A 72-year-old man with general weakness visited the outpatient clinic of the hematology department. The patient had been treated under the diagnosis of autoimmune hemolytic anemia for 2 years. His hemoglobin level at the time of the visit was 6.3 g/dL, and a blood transfusion was requested to treat his anemia. The patient's blood type was A, RhD positive. Antibody screening and identification test showed agglutination in all reagent cells with a positive reaction to autologous red blood cells (RBCs). He had a prior transfusion history with three least incompatible RBCs. The patient returned home after receiving one unit of leukoreduced filtered RBC, which was the least incompatible blood in the crossmatching test. After approximately five hours, however, fever, chills, dyspnea, abdominal pain, and hematuria appeared and the patient returned to the emergency room next day after the transfusion. The anti-Fy(a) antibody, which was masked by the autoantibody, was identified after autoadsorption using polyethylene glycol. He was diagnosed with an acute hemolytic transfusion reaction due to anti-Fy(a) that had not been detected before the transfusion. In this setting, it is necessary to consider the identification of coexisting alloantibodies in patients with autoantibodies and to become more familiar with the method of autoantibody adsorption.
Abdominal Pain ; Adsorption ; Aged ; Agglutination ; Ambulatory Care Facilities ; Anemia ; Anemia, Hemolytic, Autoimmune* ; Autoantibodies ; Blood Transfusion ; Chills ; Diagnosis ; Dyspnea ; Emergency Service, Hospital ; Erythrocytes ; Fever ; Hematology ; Hematuria ; Humans ; Isoantibodies ; Masks ; Mass Screening ; Methods ; Polyethylene Glycols ; Transfusion Reaction*

A 22-year old female patient with systemic lupus erythematosus presenting microangiopathic hemolytic anemia was treated with therapeutic plasma exchange 23 times. The patient's condition and laboratory findings (aspartate aminotransferase, alanine aminotransferase, ferritin, total bilirubin, and lactate dehydrogenase) did not improve despite the initial 18 therapeutic plasma exchange treatments. Thrombotic thrombocytopenic purpura was ruled out due to normal ADAMTS-13 activity test result; hemophagocytic lymphohistiocytosis was diagnosed based on fever, splenomegaly, pancytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis in bone marrow aspiration. The patient's condition improved rapidly upon treatment with a combination of immunosuppressants and cytotoxic agents, and more therapeutic plasma exchanges were performed five consecutive times with prolonged intervals in between. We observed that therapeutic plasma exchange treatment alone was not effective enough to treat hemophagocytic lymphohistiocytosis, unlike thrombotic thrombocytopenic purpura. Therefore, it is necessary to determine and start drug administration promptly in the treatment of hemophagocytic lymphohistiocytosis with thrombotic microangiopathy.
Alanine Transaminase ; Anemia, Hemolytic ; Bilirubin ; Bone Marrow ; Cytotoxins ; Female ; Ferritins ; Fever ; Humans ; Hypertriglyceridemia ; Immunosuppressive Agents ; Lactic Acid ; Lupus Erythematosus, Systemic ; Lymphohistiocytosis, Hemophagocytic ; Pancytopenia ; Plasma Exchange ; Plasma ; Purpura, Thrombotic Thrombocytopenic ; Splenomegaly ; Thrombotic Microangiopathies