Transfusion Strategy of RhD-negative/variant Patients in the Korean Population

The prevalence of RhD-negative individuals in the Korean population is approximately 0.15-0.30% and the supply of RhD-negative blood often faces potential shortage. Furthermore, 15-17% of serologically RhD-negative Korean individuals were revealed to be DEL variants and should be treated as RhD-positive when being considered as blood donors. This change is expected to result in a further shortage of RhD-negative blood supply, whereas surplus DEL variant blood stock is created. Therefore, it is now required to amend blood donation and supply policies, and transfusion strategies. In this review, a new transfusion strategy for patients with RhD-negative or variant blood in Korea is discussed, with particular interest in women of child-bearing age, patients with anti-D, and Asia type DEL (c.1227G>A) variants.

Report on External Proficiency Testing for the ABO and D Blood Group Typing Tests in Blood Centers (2015) / 대한수혈학회지

BACKGROUND: The Korean Blood Safety Commission has implemented external proficiency testing (PT) for blood grouping test (BGT) since 2011. We analyzed the results of 2015 PT for BGT including hemagglutination grade for ABO BGT to help in planning the future PT for BGT and improving the quality of blood centers (BC). METHODS: Two kinds of whole blood survey samples composed of three panels for ABO grouping and three panels for D typing were sent to 68 institutes. Evaluation criteria for BGT were as follows: 'Good' for the answers matched with intended results, 'Acceptable' for the consensus answers other than that of 'Good', 'Unacceptable' for the answers other than those of 'Good+acceptable' as correct answers. RESULTS: The answer rates of 'Unacceptable' for ABO BGT were 0% for A(A1) antigen (Ag), 1.5% for B Ag, and 1.5% for ABW (A2BW) Ag, 15% of blood centers were graded as 'Acceptable' for ABW (A2BW) Ag because they could not detect BW Ag. All answers for D typing were 'Good' except one institute reported wrong switched results as D positive and D negative. Hemagglutination grade for ABO BGT varied from 77.2%~100% depending on blood groups and laboratories. CONCLUSION: Because some hospital BC could not detect BW Ag and there was a clerical error, continuous education should be required, and comparison of hemagglutination grade for ABO BGT of each BC would be helpful in improving quality of BC.

Results of Proficiency Tests for HBsAg and Anti-HCV as the Blood Donor Screening Testing (2012~2015) / 대한수혈학회지

BACKGROUND: Donor screening test is one of the most important processes for blood safety management. Korea Center for Disease Control and Prevention (KCDC) has been conducting an annual proficiency test program that includes the distribution of specially manufactured panels for hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (anti-HCV) to blood centers. Here, KCDC reports the results of these proficiency tests for HBsAg and anti-HCV blood donor screening for all licensed blood centers in Korea between 2012 and 2015. METHODS: Panels for the proficiency tests were manufactured and distributed to blood centers by Chung-Ang University Hospital, which has been participating in the Korea Blood Safety Commission. Well-proven reactive sera and healthy donor's sera acquired from the Human Serum Bank in Chung-Ang University were used to make the panels. To identify the S/CO ratio of the panel, three medical institutes triple-checked the results of each panel. RESULTS: Most blood centers reported correct answers for the proficiency test with six panels. The average percentages (year) of correct answers were as follows: 98.7% (2012), 98.5% (2013), 99.1% (2014) and 99.6% (2015) for the HBsAg proficiency tests; and 97.7% (2012), 99.5% (2013), 99.1% (2014), and 99.8% (2015) for the anti-HCV proficiency tests. CONCLUSION: To improve the blood center's ability for donor screening tests, KCDC will continue the proficiency test program by managing specialized panels for HBsAg and Anti-HCV tests. Furthermore, we will investigate the level of satisfaction to improve the quality of the program.

The Change in Distribution of Red Blood Cell Antigens in Korean Youth: In an Era of Multicultural Society / 대한수혈학회지

BACKGROUND: It is important to check the blood group antigens to ensure the safety of blood transfusions. Recently, the number of multicultural families and foreigners has increased in Korea; therefore, a survey for red blood cell antigens for multicultural families is need. We performed a phenotyping of their red blood cell antigens and found the characteristics in providing basic data. METHODS: We recruited young people under the age of 26 years from multicultural family between September 2015 and March 2016. The participants were divided into two groups: the multicultural youth group (MCY) and the non-multicultural youth group (non-MCY). Subjects underwent phenotyping of ABO, Rh, Kell, Kidd, Duffy, MNS, and Diego blood group, and the results were compared and characterized between the two groups. RESULTS: A total of 226 subjects (89 MCY, 137 non-MCY) were recruited. The blood groups with differences between MCY and non-MCY were E, e in Rh and S in MNS. In MCY, the frequency of CDe expression in the Rh blood group was higher and the cDE expression was lower. There were 3.4% and 2.2% of MCY with no expression of Fy(a) and s, respectively, which were rare blood types in Koreans. CONCLUSION: The difference in frequency of red blood cell antigens between MCY and non-MCY have been identified. These results suggest that the national blood policy reflects an increasing number of multicultural families and Korea needs to be prepared for a population change.

Current Status of Pretransfusion Tests and Equipments in Small and Medium Sized Hospitals in Korea / 대한수혈학회지

BACKGROUND: The appropriate procedures and equipment for the pretransfusion test are fundamental to a safe blood transfusion. The present study aimed to assess the current status of procedures and equipment for pretransfusion tests at small- and medium-sized medical institutions, as well as to use this basic raw data to better manage blood transfusions at these institutions. METHODS: Offline and online questionnaire surveys were performed at institutions that used between 24 and 1,000 units of blood products in 2014. A total of 338 institutions participated, and the survey results were subsequently analyzed. RESULTS: Among 307 institutions where on-site ABO blood typing was performed, 15.0%, 2.1%, and 43.5% did not conduct ABO serum typing, RhD typing, and irregular antibody screening tests, respectively, and 12.8% only conducted the saline phase for crossmatching. Moreover, among 338 institutions, only 66.7% of blood banks had centrifuges, 84.5% had 37℃ incubators, 41.1% had slide view boxes; in addition, 66.1% and 18.6% had refrigerators and deep freezers, respectively, for blood storage. CONCLUSION: Certain small- and medium-sized institutions did not have the essential equipment required to operate as blood banks. Moreover, they also needed to improve their testing procedures. To address these issues, the initiation of systematic training programs and the employment of institutional strategies are necessary to enhance testing procedures and equipment, respectively.

Serious Adverse Transfusion Reactions Reported in the National Recipient-Triggered Trace Back System in Korea (2006-2014)

BACKGROUND: Adverse transfusion reactions (ATRs) are clinically relevant to patients with significant morbidity and mortality. This study aimed to review the cases of ATR reported in the recipient-triggered trace back system for a recent nine-year period in Korea. METHODS: Nine-year data obtained from 2006 to 2014 by the trace back system at the Division of Human Blood Safety Surveillance of the Korean Centers for Disease Control (KCDC) were reviewed. The suspected cases were assessed according to six categories: (i) related to, (ii) probably related to, (iii) probably not related to, (iv) not related to transfusion, (v) unable to investigate, and (vi) under investigation. RESULTS: Since 2006, 199 suspected serious ATRs were reported in hospitals and medical institutions in Korea, and these ATRs were reassessed by the division of Human Blood Safety Surveillance of the KCDC. Among the reported 193 cases as transfusion related infections, hepatitis C virus (HCV) infection (135, 67.8%) was reported most frequently, followed by hepatitis B virus (HBV) infection (27, 13.6%), HIV infection (13, 6.5%), syphilis (9, 4.5%), malarial infection (4, 2.0%), other bacterial infections (3, 1.5%), HTLV infection (1, 0.5%), and scrub typhus infection (1, 0.5%), respectively. Of the 199 cases, 13 (6.5%) cases were confirmed as transfusion-related (3 HCV infections, 3 malarial infections, 1 HBV infection, 2 Staphylococcus aureus sepsis, 3 transfusion-related acute lung injuries, and 1 hemolytic transfusion reaction). CONCLUSIONS: This is the first nationwide data regarding serious ATRs in Korea and could contribute to the implementation of an effective hemovigilance system.

Transfusion Strategy and Laboratory Update on the DEL Variant / 대한수혈학회지

Red cells that express extremely low levels of D antigen that cannot be detected by routine serologic tests are designated as DEL. Most DEL blood donors are typed as D-negative. However, DEL red blood cells can be recognized by serological adsorption and elution test or molecular RHD genotyping. Anti-D production in patients with D-negative who received transfusion containing DEL blood has reported, therefore distinction between DEL variant and true D- negative is clinically important. This review highlights a transfusion strategy and laboratory update on the DEL variant in the Korean population.

Report on External Proficiency Testing for the ABO and D Blood Group Typing Tests in Blood Centers (2014) / 대한수혈학회지

BACKGROUND: Korean Blood Safety Commission has implemented external proficiency testing (PT) for blood grouping test (BGT) to help improve the quality of blood centers since 2011. We analyzed the results of 2014 PT for BGT to help in planning the future PT for BGT and to improve the quality of blood centers. METHODS: Whole blood survey samples including three panels for ABO grouping and three panels for D typing were sent to 69 institutes. Evaluation criteria for BGT were as follows: 'Good' for answers matched with intended results, 'Acceptable' for correct answers other than that of 'Good', 'Unacceptable' for answers other than those of 'Good+acceptable' as correct answers; and 'Not graded' for answers in case of different answers in the two standard laboratories. RESULTS: All of the answer rates of 'Good' for D typing were 100%. However, the answer rates of 'Good' for cell typing, serum typing and interpretation for 14-ABO-2 samples with discrepant result between cell typing and serum typing were 39.1%, 29%, and 47.8%, respectively. Those of 'Unacceptable' for cell typing and interpretation for 14-ABO-2 samples were 2.8% and 1.4%. CONCLUSION: Because the answer rates of ABO grouping for samples with discrepant result between cell typing and serum typing were not high, education for this case is needed. Diversity of materials for PT would be necessary for more accurate evaluation of the performance of BGT in blood centers.

Analysis Survey on Changes in Hospital Blood Donation Center and Satisfaction Level with the Korean Red Cross / 대한수혈학회지

BACKGROUND: Blood supply circumstances in Korea have changed in recent decades because of blood supplier diversification and restructuring of hospital blood donation centers. The purpose of this study is to understand the current status of hospital blood donation centers and their satisfaction levels with the Korean Red Cross Blood Center (KRCBC) and compare with the previous results for sustainable development of the blood supply system. METHODS: During one month in November 2014, we conducted a questionnaire survey through e-mail in 64 hospital blood donation centers which are approved by government. The response rate was 97% (62/64 hospitals). Responses from 62 hospitals were analyzed. RESULTS: The number of hospital blood donation centers were reduced by half from 129 in 2004 to 64 in 2014. There was no blood donation center in hospitals less than 400 beds, except 2 hospitals; 23 hospital (37.1%) blood banks collected no blood components. More than 80% of hospitals were satisfied with the KRCBC service such as donor record lookup and nucleic acid amplification Test (NAT) results lookup. Hospitals with more than 1,000 beds replied that they would not take account of transferring the collection services to KRCBC because of the directed and autologous donation and unexpected emergency blood transfusion. CONCLUSION: The government should be the subject of national blood policy and establish a committee or agency for its comprehensive and consistent execution through close cooperation with the KRCBC and hospitals.

Report on External Proficiency Testing for the ABO and D Blood Typing in Blood Centers in 2012 and 2013 / 대한수혈학회지

BACKGROUND: It was reported that a continuous education program and external proficiency testing (PT) for blood grouping test (BGT) might be necessary because some blood centers of medical institutions could not correctly examine ABO subtype and D variant, according to the results of the first year project in 2011. Therefore, the results of PT for BGT in blood centers in 2012 and 2013 were compared to those in 2011 in order to assess the impact of projects during a period of three years and to help in planning the future PT for BGT. METHODS: Whole blood survey samples composed of three panels for ABO grouping and three panels for D typing were sent to 74 and 71 institutes in 2012 and 2013, respectively. Evaluation criteria for BGT were as follows: 'Good' for the answers matched with intended results, 'Acceptable' for the correct answers other than that of 'Good', and 'Unacceptable' for the answers other than those of 'Good+acceptable' as correct answers. RESULTS: The answer rates of 'Unacceptable' for ABO subtype were 1.4% in 2012 and 4.2% in 2013. However, the answer rate of 'Good' increased from 44.6% in 2012 to 83.1% in 2013. The answer rate of 'Unacceptable' for D variants showed a marked decrease, from 16.2% in 2012 to 1.4% in 2013. CONCLUSION: Projects for PT for BGT during a period of three years have improved laboratory quality in blood centers. However, the acquisition and change of the materials for PT would be necessary in order to continuously and practically provide help to blood centers.

The Status of the Korea Blood Inventory Monitoring System, 2009~2012 / 대한수혈학회지

BACKGROUND: In the Republic of Korea, due to the low birth rate, blood donation is expected to decrease. However, the demand for blood is increasing as the proportion of elderly has increased. Korea Centers for Disease Control and Prevention operate the Korea Blood Inventory Monitoring System (KBIMs) for detection and response to the shortage of blood. The aim of this study was to show the trend of blood supply monitored by KBIMs. METHODS: This study analyzed the red blood cell inventory ratio, average daily usage, time-lag from blood donation to transfusion and from receipt to transfusion in blood banks monitored by KBIMs from 2009 to 2012. RESULTS: A total of 25 hospitals have participated in KBIMs since 2009. The average inventory ratio of blood banks was 5.3 days. By month, the inventory ratio was highest between November and February; and by week, highest on Fridays. Daily amount of RBC utilized in hospitals peaked on Thursday by week. Time-lag from blood donation to transfusion and from receipt to transfusion in blood banks was 12.2 and 6.4 days, respectively. The inventory ratio of type-A RBC was the lowest, because of the highest level of demand. In addition, time-lags from blood donation to transfusion and from receipt to transfusion were shortest in type-A RBC. CONCLUSION: The inventory ratio in blood banks monitored by KBIMs was stable throughout the years. However, due to higher level of demand, there is a risk of shortage of type-A RBC.

Clinical characteristics of acute Q fever in Daegu area / 대한내과학회지

BACKGROUND/AIMS: Although only a few sporadic cases of Q fever have been reported in Korea, a total of 13 cases have been seen in our area. We performed this study to evaluate the clinical characteristics of these cases of acute Q fever. METHODS: Demographic features, clinical manifestations, laboratory and radiologic findings, and therapeutic outcomes of all cases were evaluated. Q fever was diagnosed using an indirect micro-immunofluorescence assay (MIFA) and polymerase chain reaction (PCR). RESULTS: A total of 13 patients with acute Q fever seen from January 2006 to August 2008 at three teaching hospitals in the Daegu Metropolitan City area were enrolled. The mean age was 49 years old (range, 24~76), and the male to female ratio was 11:2. Six (46.2%) cases had a history of animal contact. Fever (100%) was the most common manifestation, followed by myalgia (84.6%), headache (61.5%), anorexia (61.5%), and chills (61.5%). All cases were diagnosed with high titers of anti-phase II antibody (IgM> or = 1:50, IgG> or =1:200) and positive nested PCR for the 27-kDa OMP com-1 gene of Coxiella burnettii in the blood. In three cases, liver biopsies revealed the presence of compact fibrin-ring granulomas. No characteristics of pneumonia were diagnosed on chest X-rays. The predominant presentation was acute febrile illness with hepatitis, including three cases (27.3%) of severe cholestatic hepatitis. The most frequently used antimicrobial agent was doxycycline (84.6%), followed by azithromycin (7.7%). CONCLUSIONS: Acute Q fever may be added to the list of differential diagnosis of patients with acute febrile illness and hepatitis in the Daegu Metropolitan City area.

Seroprevalence and Risk Factors of Brucellosis among Slaughterhouse Workers in Korea / 예방의학회지

OBJECTIVES: The incidence of zoonoses in Korea has increased recently. However, the study of high risk groups for zoonoses has not been conducted to date in Korea. Thus, we did this study to obtain data on brucellosis among slaughterhouse workers in Korea. METHODS: We evaluated the structure of slaughterhouses and the process of slaughtering by reviewing the relevant literature and doing field studies. We visited 73 slaughterhouses and 62 residual products handle houses across the country. In addition, we conducted a questionnaire survey of the work activities, and obtained blood samples in order to determine the seroprevalence and risk factors of brucellosis. The titers of brucellosis antibodies were measured using the standard tube agglutination test (SAT). We diagnosed subjects as seropositive for Brucellosis if the titers were more than 1:160. The data collected was evaluated using SPSS ver. 17.0. RESULTS: We included 1,503 subjects and obtained 1,482 blood samples among them: 849 workers involved in slaughtering, 351 handlers of residual products, 190 inspectors and their assistants, and 92 grading testers and their assistants. The seroprevalence of brucellosis among the slaughterhouse workers was 0.8% (95% CI=0.4-1.5). Broken down, the seroprevalence of brucellosis among the workers involved in slaughtering was 0.7% (95% CI=0.3-1.6), the handlers of residual products was 1.7% (95% CI=0.7-3.9) respectively. Risk factors for contracting brucellosis among slaughterhouse workers were being splashed with cattle blood around the mouth, cattle secretions around the body and not putting on protective apron while at work. CONCLUSIONS: An educational program is needed for high risk groups on zoonoses about the prevention of infection. Thus, effective working guidelines for workers who participate in the slaughter of animals must be developed in order to protect them from zoonoses.

A case of acute Q fever with fibrin-ring granuloma in the bone marrow and lymph node biopsy / 대한내과학회지

Q fever is a zoonotic infection caused by Coxiella burnetii. Acute Q fever usually develops as a self-limited flu-like illness, atypical pneumonia, or hepatitis. We experienced a case of Q fever in a 50-year-old male who had a prolonged fever. The bone marrow and lymph node biopsy revealed fibrin-ring granulomas, which is a distinct finding of Q fever. The diagnosis was proven by high titers of C. burnetii anti-phase II antibody (IgM 1:512 and IgG >,048) and positive nested PCR for the com-1 gene. Q fever is rare in Korea, but should be considered in the differential diagnosis of fever of unknown origin

Brucella Endocarditis with Splenic Abscess: A Report of the First Case Diagnosed in Korea

Human brucellosis has a broad spectrum of clinical manifestations, which includes endocarditis, a focal complication that is uncommon yet responsible for the majority of associated deaths. The most successful treatment outcomes of Brucella endocarditis have been reported with usage of both antimicrobial agents and surgery. However, there are few reports on the treatment of Brucella endocarditis using antibiotics only. We report the first case in Korea of Brucella endocarditis with aortic valve vegetations and an accompanying splenic abscess, which were treated successfully with antibiotic therapy alone.

Q fever as a cause of fever of unknown origin / 대한내과학회지

Q fever is an orthozoonotic infection caused by Coxiella burnetii, which was recently reclassified from the order Rickettsials to the order Legionellales. Although Q fever is usually mild and self-limiting, it may be manifested as a serious disease, such as pneumonia, endocarditis, or meningoencephalitis. We describe three separate cases of acute Q fever, which were diagnosed by an indirect micro-immunofluorescence assay (MIFA) test and DNA amplification (PCR). Three adult patients were admitted between December 2004 and August 2006 because of a fever of greater than three weeks duration. Only one patient had contact history with a dog. Of the three patients, two patients had myalgia, headache, skin rash, lymphadenopathy, and hepatosplenomegaly. Although all sets of blood cultures were negative, anti-phase II antibody titers by using an indirect MIFA (IgG 1:512 - 1,024 and IgM 1:320) were markedly increased in sera from all of three patients. Concomitant PCR assays also demonstrated the presence of OMP com1 for C. burnetii in blood from all of the three patients. Two patients had complete resolution of symptoms and signs with a two week course of doxycycline, while one patient had spontaneous defervescence. Although the incidence of Q fever is not well known yet in Korea, it should be considered in the differential diagnosis of patients with fever of unknown origin.

Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the Pohang isolate

We investigated the immune response induced by the Francisella (F.) tularensis live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA analysis were carried out for the comparative study of the cytokines, including TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at 120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times higher level of IFN-gamma than the respective levels at the early time points after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5 times lower than those induced by the Pohang isolate. Also, the organs from the Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL-12 than the levels in the LVS-infected mice. The blood from the Pohang-infected mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10 was also increased by 4 times at 96 h compared to an early infection time point, while IL-4 was not induced during the whole infection period. These results suggest that F. tularensis may induce a Th1-mediated immune response to in vivo infection and the Pohang isolate has a higher capacity than the LVS to induce an acute immune response in Blab/c mice.

Spontaneous Bacterial Peritonitis due to Brucella abortus in a Cirrhotic Patient in Jeju Island

Spontaneous bacterial peritonitis is the common infectious disease in liver cirrhosis patients with a fever. Brucellosis is a rare cause of bacterial peritonitis. A case indigenous to a citizen of Jeju, he ate a raw veal of cow four times in last 2 months prior to admission. The gram-negative bacilli were isolated from blood and peritoneal fluid cultures. He was confirmed brucellosis by serologic work- ups. This isolate was confirmed as Brucella abortus by using PCR amplification of 16S ribosomal RNA (rRNA) and omp2. This is the first case of bruellosis that was diagnosed spontaneous bacterial peritonitis in liver cirrhosis patient among native korean citizens. Successful treatment was obtained by using a regimen of doxycycline and gentamicin. Brucella should be suspected as a cause of spontaneous bacterial peritonitis in cirrhotic patients with no response to standard spontaneous bacterial peritonitis treatments.

Spontaneous Bacterial Peritonitis due to Brucella abortus in a Cirrhotic Patient in Jeju Island

Spontaneous bacterial peritonitis is the common infectious disease in liver cirrhosis patients with a fever. Brucellosis is a rare cause of bacterial peritonitis. A case indigenous to a citizen of Jeju, he ate a raw veal of cow four times in last 2 months prior to admission. The gram-negative bacilli were isolated from blood and peritoneal fluid cultures. He was confirmed brucellosis by serologic work- ups. This isolate was confirmed as Brucella abortus by using PCR amplification of 16S ribosomal RNA (rRNA) and omp2. This is the first case of bruellosis that was diagnosed spontaneous bacterial peritonitis in liver cirrhosis patient among native korean citizens. Successful treatment was obtained by using a regimen of doxycycline and gentamicin. Brucella should be suspected as a cause of spontaneous bacterial peritonitis in cirrhotic patients with no response to standard spontaneous bacterial peritonitis treatments.

The First Case of Human Brucellosis in Korea

Brucellosis is usually transmitted to human by direct contact with infected animals or by ingestion of unpasteurized dairy products. Because of the wide spectrum of its clinical manifestations, brucellosis may appear as other infections and asymptomatic conditions and, therefore, the diagnosis of the disease is frequently missed or delayed. A 41-years-old livestock worker was attended at a local clinic with headache, undulating fever, fatigue, weight loss presentations but the symptoms were not improved in spite of symptomatic therapy of the disease for 6 weeks. Epidemiological background showed that the patient had often ingested unpasteurized cow milk. We confirmed Brucella abortus infection by STA, ELISA and PCR methods. Symptomatic therapy of the disease with appropriate antibiotics (streptomycin, doxicyclin), had favourable outcome. It's the first case report of human brucellosis caused by direct contact of brucella infected milk cow or ingestion of raw milk in Korea, since its original identification in 1939.