To improve the supply and management of fresh frozen plasma (FFP), we started thawing FFP in the Department of Blood Transfusion in October 2015. We retrospectively analyzed and compared the units of ordered and transfused FFP before and after October 2015. In the 9 months before FFP thawing was started in the Department of Blood Transfusion, 14,121 units of FFP were ordered and 7,149 units were transfused. In the 9 months after October 2015, 9,399 units of FFP were ordered (33.4% reduction) and 5,522 units were transfused (22.8% reduction). Therefore, significant decreases in ordered and transfused units of FFP were observed after FFP thawing was started in the Department of Blood Transfusion. Both the usage rate among FFP units ordered (50.6% vs. 58.8%) and the proportion of cases with prothrombin time < 30%, a trigger for FFP transfusion described in the guideline, at the time of FFP order (10.6% vs. 18.2%) were significantly higher after October 2015. These results suggest that clinicians improved their ordering and transfusion of FFP units based on clinical situations after FFP thawing was started in the Department of Blood Transfusion.
Recently, to cope with the decrease in donor population, a program was installed into the blood component collection device "Trima Accel" to allow the collection of double the 10 units of platelet concentrate (PC) from a single donor. Although 10-unit PC collections are usually stored in a poly-vinyl chloride (PVC) bag, this new program requires twice this amount (PC source) to fit into the same PVC bag. A polyolefin (PO) bag is also available for 10-unit PC storage. The PC source is divided into two aliquots on the day of blood collection (Day 1) or the next day (Day 2). Here, we studied the quality of 10-unit PC divided on Day 2.
There was no significant difference between the quality of divided PC and conventional non-divided PC except for the C5a concentration and pH during a 3-day storage period. Both C5a and pH were within the normal range.
In conclusion, the quality of 10-unit PC divided from the PC source was similar to that of conventional PC.
In Japan, the use of cord blood as a source of stem cells for transplantation has increased every year since the first unrelated cord blood transplantation was carried out in 1997. At the Japanese Red Cross Kanto-Koshinetsu Cord Blood Bank, we use a cryoprotective agent comprising 8% dimethyl sulfoxide (DMSO) containing 0.8% dextran (8D0.8D) to cryopreserve umbilical cord blood. Given that cord blood is usually transplanted to a recipient without washing, DMSO is also infused with cord blood intended for the recipient. Because DMSO has toxic effects on the human body, it is used at as low a concentration as possible. Polysaccharide dextran is also a reported anaphylactic factor in clinical cases.
In this study, we examined new cryoprotectant formulations comprising a mixture of monosaccharide glucose in DMSO instead of dextran: 5% DMSO-1.5% glucose (5D1.5G) and 8% DMSO-1.5% glucose (8D1.5G). Cryoprotection with 5D1.5G produced significantly higher recovery and viability rates of CD34+cells compared to that with 8D0.8D. In addition, cryoprotection with 5D1.5G showed significantly higher recovery rates of nucleated cells and CD34+cells than that with 8D1.5G. Our results suggest that the new cryoprotectant 5D1.5G may effectively replace 8D0.8D for cryoprotection of cord blood.
The subcommittee on Safety for Plasma-Derived Products, Ministry of Health, Labour and Welfare established Japanese National Standards for quality control of viral Nucleic Acid Amplification Tests (NATs) for human blood products for transfusion and plasma derivatives used in Japan continuously from 1999. The standards are provided by the National Institute of Infectious Diseases. We calibrated the relative potency of the first National Standards for Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) NATs against the World Health Organization (WHO) International Standard using the end-point method, according to the WHO international collaborative study then. In Japan, in addition to revision of the NAT guideline and sensitivity for implementing individual donor NATs for screening blood products for transfusion, the detection sensitivity of viral NATs was revised in 2014. This increased the need to reevaluate the National Standards for viral NATs for the latest polymerase chain reaction (PCR) assay. We also reevaluated the assigned titers of the first National Standards for HBV-DNA, HIV-RNA, and HCV-RNA by multi-institutional collaborative studies in the three years from 2014 to 2016. Based on accurate measurements using the current, highly accurate quantitative PCR assay, the titers of the first Japanese National Standards were revised to 1,060,000 IU/ml for HBV-DNA, 75,000 IU/ml for HIV-RNA, and 260,000 IU/ml for HCV-RNA in the studies. Effective use of the National Standards reassigned to more reliable titers is expected to progress and improve quality control for NATs.
Granulocyte colony-stimulating factor (G-CSF) is generally used for peripheral blood stem cell (PBSC) mobilization. However, poor mobilization is observed in patients in whom G-CSF is ineffective. Recently, plerixafor, which mobilizes significant amounts of PBSC into the circulation, has been used to mobilize PBSCs for autologous transplantation. To select patients requiring the use of plerixafor, we aimed to predict poor PBSC mobilization using hematopoietic progenitor cell (HPC) counts measured by the XN-9000 automated hematology analyzer (Sysmex) the day before harvest. Thirty-four patients were administered G-CSF or G-CSF plus chemotherapy for mobilization, and the HPC count was measured the day before harvest (preHPC). Patients were divided into 4 groups based on their preHPC levels: (i) 0-5/μl (n=8), (ii) 6-10/μl (n=7), (iii) 11-20/μl (n=6), and (iv) >21/μl (n=13). The proportion with poor mobilization in the groups was 25%, 14%, 0%, and 0%, respectively. Moreover, sufficient PBSCs could not be harvested from several patients with preHPC ≤ 20/μl. Therefore, we concluded that patients with preHPC ≤ 20/μl may potentially show poor mobilization, and patients with preHPC ≤ 10/μl had a higher probability of showing poor mobilization.
The Japan Society of Transfusion Medicine and Cell Therapy has published "Protocol for the in-house production of cryoprecipitates". However, the most effective way of recovering fibrinogen (Fbg) from Fresh Frozen Plasma-Leukocytes Reduced (FFP-LR) samples remains controversial.
We conducted experiments to determine the optimum conditions for increasing Fbg recovery. Recovery rates of Fbg were compared for each of the following conditions: the number of thawing cycles (one or two), thawing time (18 hrs or 24 hrs), centrifugal rotation speed (low or high), refrozen state of FFP-LR samples after thawing (complete or incomplete), and storage temperature (-30°C or -80°C).
Recovery rates of Fbg were 16%, 6% and 20% higher when samples were thawed twice, thawed for 18 hrs, and completely refrozen compared to being thawed once, thawed for 24 hrs and incompletely refrozen, respectively. Freezing after preparation at -30°C decreased Fbg recovery by 36% compared to that at -80°C.
We concluded that the optimum conditions for high Fbg recovery were thawing FFP-LR samples for 18 hrs, refreezing completely, thawing again for 18 hrs, then centrifuging at low or high speed to precipitate the cryoprecipitate before storing at -80°C.
The rare blood type Jr (a-) is in high demand. We screened the blood of 400,000 donors for the Jr (a) antigen. The frequency of Jr (a-) was 134/238,797 (0.065%) males and 104/159,263 (0.056%) females. The total number of donors with the Jr (a-) phenotype was 238/400,000 (0.060%). There was no difference in the prevalence of Jr (a-) between the sexes or among the areas of Japan. All 35 (33.7%) donors with anti-Jra antibodies were female. Therefore, anti-Jr antibodies may be produced by immunization during pregnancy and delivery. Thirty-three of the 35 donors (94.3%) were positive for anti-Jra antibodies alone. The anti-Jra titer was between 1:8 and 1:512 dilution, and a titer of 1:256 dilution (12/35) was the highest. We succeeded in analyzing the IgG subclass of 14 of the anti-Jra-positive cases; all 14 (100%) had IgG1 and 3 also had weak IgG3.
Introduction: Anaphylactic shock accounts for 20% of the 1,500 non-hemolytic transfusion reactions reported annually in Japan. Here, we report a case of anaphylactic shock that was prevented following the transfusion of washed platelets. Case: A 41-year-old man received an allogeneic stem cell transplantation for myelodysplastic syndromes and became resistant to platelet transfusion soon after transplantation due to anti-human leukocyte antigen (HLA) antibodies. On the 19th day after transplantation, he developed lip edema and dyspnea, and his blood pressure decreased 15 minutes after the start of platelet transfusion. He was diagnosed with anaphylactic shock and transfusion was discontinued. Bleeding tendency continued, after premedication, HLA-matched platelets were transfused the next day; however, he again exhibited anaphylactic shock 15 minutes after the start of transfusion. We received washed platelets from the Japanese Red Cross Society and transfusion of the washed platelets on the 24th day did not result in anaphylactic shock; pre-transfusion medication therefore became unnecessary. Discussion: Transfusion of washed platelets prevented the occurrence of allergic reactions. While loss of platelets during washing was a concern, the hemostatic effects were sufficient. Washed platelets became available in Japan in September 2016, and should be used for patients with anaphylaxis.
A 59-year-old woman had myelodysplastic syndrome (MDS) complicated by direct antiglobulin test (DAT) -negative hemolysis that resulted in transfusion-dependent anemia. During her clinical course, the DAT became positive, and the efficacy of transfusion diminished. Transfusion using blood units compatible with Rh and Kidd blood types led to improved efficacy of transfusion for several months, but the patient's anemia worsened with increasing DAT avidity, leading to the diagnosis of autoimmune hemolytic anemia (AIHA). Administration of prednisone improved her AIHA, and the patient no longer required blood transfusions 4 months after initiation of treatment. Patients with DAT-negative hemolysis associated with MDS should be followed by repeated serological testing. Furthermore, clinicians should consider the possibility of DAT-negative-AIHA development because prednisone is reportedly effective against this type of anemia and can reduce the need for blood transfusions.
Acquired hemophilia A is a hemorrhagic disorder characterized by the development of anti-factor VIII antibodies and disproportionately prolonged activated partial thromboplastin time (APTT). Here, we report a patient who developed acquired hemophilia A during administration of oral anticoagulants. A 66-year-old male had been taking warfarin for over 10 years and was subsequently administered rivaroxaban for three years for thromboprophylaxis associated with atrial fibrillation. Because of the occurrence of repeated subcutaneous bleeding, rivaroxaban was changed to apixaban, which was changed back to warfarin. Finally, warfarin was also discontinued due to continuous bleeding tendency and prolonged APTT and prothrombin time-international normalized ratio (PT-INR). Although PT-INR went back to normal after cessation of warfarin, APTT remained prolonged and caused life-threatening massive intramuscular bleeding. Acquired hemophilia A was diagnosed based on several coagulation examinations. After admission, the patient was treated with immunosuppressive therapy comprising cyclophosphamide and prednisolone, and bypass therapy using activated prothrombin complex concentrate (APCC). An increase in the number of acquired hemophilia patients due to treatment with anticoagulants may arise as a consequence of the aging population. Extreme care should be taken to diagnose hemorrhagic disorders when administering agents that affect clinical coagulation tests to avoid unnecessary usage of blood products.