Practical Considerations in Convalescent Plasma Therapy for Coronavirus Disease 2019

Convalescent plasma therapy has been used to achieve passive immunization against diverse infectious agents by administering pathogen-specific antibodies. Coronavirus disease 19 (COVID-19), which originated in Wuhan, China, has recently become a major concern all over the world. There are no specific treatment recommendations for COVID-19 because of the lack of knowledge and evidence about this virus. Convalescent plasma therapy can be used as an empirical and investigational treatment for COVID-19, and so we briefly describe the main issues related to convalescent plasma therapy from the perspective of transfusion medicine.ope

Therapeutic Plasma Exchange in a Patient with Hemophagocytic Lymphohistiocytosis

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.ope

Blood Supply and Demand in Korea: What Is in Store for the Future?

Purpose: Presently, Korea is facing new challenges associated with an imbalance in blood supply and demand. The purpose of this study was to examine trends in blood supply and demand in Korea over the past 10 years through 2018 and to propose what to prepare in the future. Materials and methods: Age demographics in Korea were analyzed using data from the Statistics Korea. Blood donation and blood supply data were analyzed using Blood Services Statistics 2018 by the Korean Red Cross. Blood transfusion data from hospitals in 2018 were obtained from the Health Insurance Review and Assessment Service. Results: In 2018, 2883270 whole blood and apheresis units were collected in Korea. The Korean Red Cross supplied 4277762 blood components to 2491 hospitals. The overall blood donation rate was 5.6%, and the most frequent donors were young male donors. Leukoreduced red blood cells (RBCs) constituted 25% of all RBCs used, and 40% of all platelets were supplied by single-donor platelets. The self-sufficiency rate of domestic plasma with which to produce plasma-derived medicinal products was 68.7% in 2018. Blood use was the most frequent among patients aged 70-79 years. Conclusion: Blood management in Korea is changing rapidly due to a low birth rate, rapid aging, and an increase in severely ill patients who require most of the blood supply. Therefore, future plans to promote donation at a national level and optimal use of blood in hospitals is necessary.ope

Case Series of Transfusion-Related Acute Lung Injury in a Tertiary Hospital and a Practical Comparison with the New Diagnostic Criteria

Background: Transfusion-related acute lung injury (TRALI) is defined as acute respiratory distress syndrome with non-cardiogenic pulmonary edema caused by transfusion. It occurs only rarely but could result in patient mortality. TRALI has been declining since the successful adoption of TRALI risk mitigation strategies in several countries. The new diagnostic criteria were suggested in 2019 based on the knowledge and experience gained throughout the last decade. This article integrated a series of TRALI cases diagnosed in a tertiary hospital while reviewing each case based upon the new diagnostic criteria. Methods: Among the reported transfusion adverse reactions that occurred from March 2013 to June 2019, seven TRALI cases were recruited for this study. Each case was retrospectively reexamined with its clinical condition and transfusion history. The diagnosed cases were classified into TRALI subtypes newly suggested in the 2019 version. Results: The mean time interval to adverse reaction was 117 minutes (range: 7~370 minutes) and all satisfied the condition of hypoxemia and bilateral pulmonary infiltrations. The transfused blood components were apheresis platelets in three cases, platelet concentrates in one case, red blood cells in one case and combinations of different products in two cases. Five cases were diagnosed as possible TRALI, and all five cases were diagnosed as TRALI type 2 (2019 criteria). Conclusion: In our center, seven patients were diagnosed TRALI during the last 6 years. Screening more TRALI patients according to the new criteria, along with investigating the patients’ clinical characteristics, transfused blood components, treatments and integrated research, will facilitate Korean research on this field of medicine.ope

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.ope

OP9 세포주 공배양을 통한 역분화줄기세포 유래

There are many blood group antigens on the surface of red blood cells (RBCs). The antibodies against these blood group antigens which are called unexpected antibodies can cause acute and delayed hemolytic transfusion reactions. Therefore, it is important to detect unexpected antibodies before transfusion and prepare the appropriate blood products. However, reagent RBCs used during the unexpected antibody tests are made from donated whole blood, so the surface antigens of the reagent RBCs change with the donor. This change causes an inconsistency in the reagent RBCs’ blood group antigens. In vitro RBC production of reagents is emerging as an alternative method of acquiring RBCs to produce more consistent antigen test results. Several different methods have been developed to produce human RBCs. One source of RBCs is stem cells. Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cell that can be generated directly from adult mature cells. The iPSCs are considered to be an unlimited source because they can reproduce. This study was conducted to test a method of generating RBCs from iPSCs. It was hypothesized that in vitro cultured RBCs would express blood group antigens on the surface which would react with antibodies. The iPSCs for this study were obtained from peripheral blood mononuclear cells through reprogramming using five transcription factors. The iPSCs were differentiated by co-culturing with the OP9 cell line to produce erythrocytes. During the differentiation process, differentiation trends were observed through microscopic analysis and flow cytometry analysis. On the last day of differentiation, hemoglobin electrophoresis and oxygen-binding capacity assay were conducted to verify that the generated RBCs were functioning. Then, the reactions of the generated RBCs to antibodies were tested to confirm that the RBCs expressed blood group antigens. Cells received from six donors are well produced into iPSC showing stemness characteristics and iPSCs were able to differentiate into the erythroid lineage. Hemoglobin electrophoresis was performed on cultured RBCs and showed a high peak in the hemoglobin F region. No significant difference was observed in oxygen binding capacity assay between normal RBCs and cultured RBCs. In the case of blood group antigen test, it was confirmed that the same expression was observed between the donors’ RBCs and cultured RBCs. The blood group antigens of cultured RBCs reacted well with antibodies, which indicates that RBCs can be made from iPSCs for diagnostic purposes. 적혈구 표면에는 수많은 혈액형 항원이 존재한다. 환자의 체내에는 다양한 혈역형 항원에 대한 비예기항체가 생성될 수 있는데, 특히 임상적으로 중요한 비예기항체는 급성 및 지연성 용혈성 수혈부작용의 원인이 된다. 따라서 수혈전 비예기항체를 검출하고 이에 따라 적절한 혈액제제를 준비하는 것이 중요하다. 비예기항체 검사를 위한 시약 적혈구는 헌혈을 통해 공급되는데 제조 때마다 공혈자가 바뀜에 따라 시약 적혈구의 항원도 매번 바뀌는 결과를 초래한다. 이는 비예기항체 검사 결과의 일관성을 저해하는 요인으로서 진단시약을 위한 체외 적혈구 생산기술을 통해 검사 결과의 일관성을 유지할 수 있다면 적혈구 체외생산은 효과적인 대안으로 생각될 수 있다. 체외에서 적혈구를 생산할 수 있는 원료 중 줄기세포가 있다. 그 중 역분화줄기세포는 성인세포로부터 얻을 수 있는 줄기세포로, 자기 재생능력으로 인해 적혈구를 무한정 생산할 수 있는 잠재력이 있다. 본 연구에서 역분화줄기세포로부터 적혈구를 분화시켜 진단용 적혈구 시약을 생산하고자 하였으며, 체외에서 생산된 적혈구에서 비예기항체와 반응 가능한 혈액형 항원을 표현할 것이라는 가설을 수립하였다. 말초혈액단핵구로부터 5개 전사인자의 형질도입을 통해 역분화줄기세포를 제작하였고, OP9 세포주와 공배양을 통해 적혈구로 분화시켰다. 분화과정을 확인하기 위해 주기적으로 현미경검사와 유세포검사를 하였으며, 마지막에 헤모글로빈 전기영동시험과 산소결합능 검사를 시행하였다. 혈액형 항원 발현을 혈청학적 방법으로 검사하였다. 연구 결과, 6명 기증자로부터 기증받은 말초혈액에서 역분화줄기세포를 생산하였으며, 적혈구로의 분화를 성공하였다. 체외생산적혈구는 헤모글로빈 전기영동시험 결과 F 영역에서 피크를 보였으며, 정상적혈구와 체외생산적혈구의 산소결합능은 유의미한 차이를 보이지 않았다. 혈액형 항원을 검사한 결과 체외생산적혈구는 기증자의 원 적혈구의 항원과 동일한 혈액형 항원을 표현하고 있었다. 이번 연구를 통해 체외생산적혈구가 비예기항체와 반응 가능한 혈액형 항원을 발현하고 있음을 확인하였으며, 역분화줄기세포 유래 적혈구 진단시약의 제작 가능성을 제시하였다.open박