Feasibility evaluation of a blood rotation system for efficient blood product utilization in remote island settings.

BACKGROUND AND OBJECTIVES: Geographical limitations in remote island medical facilities result in excessive wastage of blood products. To address this, we explored the feasibility of a novel blood rotation system, which enables the return and redelivery of blood products to/from the blood bank while ensuring the management of product quality, including temperature control. This study aimed to enhance the supply of blood products to these facilities. MATERIALS AND METHODS: The Japan Red Cross Nagasaki Blood Center, Nagasaki Goto Chuoh Hospital (NGCH) and Nagasaki University Hospital collaborated to coordinate the transport and supply of red blood cell (RBC) products. Type O, RhD-positive, irradiated RBC products were stored at a precise 4.0 ± 2.0°C in an active transport refrigerator (ATR). After transport from the Japan Red Cross Nagasaki Blood Center to NGCH, RBC products were held for 1 week in the ATR, and unused products were returned. Eligible returned products were reissued to the Nagasaki University Hospital. RESULTS: All the returned RBC products met the redelivery criteria. Among the 103 redelivered RBC preparations, 101 bags (98.1%) were successfully used. NGCH utilized 597 RBC products and discarded 80 samples. The ATR supplied 107 type O RBC bags without any wastage. The overall wastage rate was 10.2% during the study period compared with 24.2% in the same period in the previous year. CONCLUSION: This innovative supply and operation system ensures a consistent and secure RBC product supply to remote islands while maximizing blood product use.

Home transfusions are implemented using diverse approaches in Japan.

BACKGROUND AND OBJECTIVES: Japan's ageing society has increased the need for home healthcare, including home transfusions. We hence aimed to elucidate the purpose and utilization of home transfusions in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The study period was February to December 2019, and information of patients receiving home red blood cell transfusions, including patient background, pre-transfusion laboratory data and the purpose of the transfusions, was collected. RESULTS: Haematological malignancies and solid tumours accounted for 70% of the patients' underlying diseases, with the former being significantly more common in urban areas. Regarding the purpose of the home transfusions, haematologists focused on symptom improvement, whereas gastroenterology surgeons focused on life support. Furthermore, maintenance of life was more likely to be the aim in the group of patients with the lowest level of activities of daily living. The main items that were significantly associated with a low haemoglobin level before transfusion included age ≥90 years and a gastroenterologist being the physician in charge. CONCLUSION: Home transfusions were found to be performed in a restrictive and diverse manner in Japan. Life support is the second most common purpose of home transfusion in Japan, and optimizing effective home transfusion remains a challenge.

A Case of Acquired Factor XIII Deficiency with Systemic Lupus Erythematosus Diagnosed after Repeated Intracerebral Hemorrhages.

We present a case of autoimmune-acquired factor XIII deficiency associated with systemic lupus erythematosus, which was diagnosed as a cause of repeated intracerebral hemorrhage. An intracerebral hemorrhage occurred in a 24-year-old female patient. Craniotomy was performed to remove the hematoma, but rebleeding occurred at the same site on days 2 and 11, respectively. Detailed blood tests revealed that factor XIII activity decreased. Although autoimmune-acquired factor XIII deficiency is a very rare disease, it can sometimes be fatal when intracerebral hemorrhage occurs. If there is repeated intracerebral hemorrhage, factor XIII activity should be confirmed.

Management system of home transfusion in Japan: A nationwide survey in 2019.

BACKGROUND AND OBJECTIVES: In Japan, there are various opinions on the pros and cons of home transfusion because of safety concerns. We hence aimed to elucidate the safety and availability of home transfusion in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The analysis period was February to December 2019. Basic information about the clinics, their collaboration system with core hospitals, storage method of red blood cells (RBCs) and the system for the management of patient information regarding transfusion reactions were investigated. RESULTS: Detailed information was obtained regarding the implementation of home transfusions by 51 clinics. The proportion of home care clinics performing home transfusions was 17.6%, and they were more frequently performed in urban regions. Approximately half of the clinics collaborated with a core hospital for emergency responses to transfusion reactions. At 84% of the clinics, RBC units were stored in refrigerators that were not exclusively allocated to blood storage. Nurses and family members were involved as patient attendants in 83% and 77% of the home transfusions, respectively. No serious transfusion reactions were reported among the 150 patients in 2019, nor the 623 patients up to 2018. CONCLUSION: From data on its availability and safety, home transfusions are considered to be in the developing phase in Japan. Increased cooperation between hospitals and clinics is crucial towards improving the home transfusion system in Japan in the future.

Transfusion-associated circulatory overload and high blood pressure: A multicentre retrospective study in Japan.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is an adverse reaction associated with a high risk of mortality. The actual incidence of TACO and hypertension associated with transfusion in Japan is unknown. METHODS: A multicentre retrospective observational study was conducted across 23 institutions during the 1-year period of 2016. Patients were included if they developed TACO or their blood pressure (either systolic or diastolic) increased by at least 30 mmHg during the transfusion. TACO was confirmed by the primary physicians and transfusion medicine teams and recorded in the data on passive surveillance, and additional data were extracted from electronic medical records. RESULTS: In our patient cohort of 31 384 patients who underwent transfusion, the incidence of TACO and hypertension was 0·03% and 0·2%, respectively. However, 43% of the participating institutions didn't report any cases. When comparing risk factors between the TACO and hypertension groups, there were significant differences in comorbidities, such as abnormal findings on chest x-ray. Significant differences between the two groups were observed post-transfusion pulse rate, body temperature and oxygen saturation (P < 0·01). In the group of patients with hypertension, the level of BNP increased significantly after transfusion in 45% (5/11) of the patients. We identified 4 patients in the hypertension group who met the new ISBT's TACO criteria. CONCLUSION: Our study suggests that more attention should be given to TACO in Japan, particularly in terms of improving surveillance systems. For the early diagnosis of TACO, it is crucial to carefully monitor vital signs including blood pressure.

Differences among hemoglobin thresholds for red blood cell transfusions in patients with hematological diseases in teaching hospitals: a real world data in Japan.

A hemoglobin (Hb) threshold level of 7 g/dL has been proposed for red blood cell (RBC) transfusion in patients with chronic anemia in the Japanese guideline since 2005. However, Hb thresholds for hematological diseases in clinical practice and factors responsible for higher Hb thresholds remain unclear. Hb thresholds were collected for patients with hematological diseases from 32 Japanese teaching hospitals. Uni- and multivariate analyses were used to analyze relationships between Hb threshold level and various patient and hospital factors. In total, 4996 units of RBC were transfused to 1054 patients with hematological diseases in 2421 transfusions. Median age was 68 years. Myelodysplastic syndrome was the most frequent diagnosis. Overall median Hb threshold level was 6.9 g/dL. Multivariate linear regression analysis detected the following variables associated with Hb threshold level: hospital; cardiovascular disease; symptomatic anemia; and hematopoietic stem cell transplantation. Hospital was the most significant factor. Collectively, median Hb threshold level in clinical practice in Japan was similar to the guidelines. Higher Hb threshold level depended on the hospitals at which the transfusions were performed as well as patient condition. Educational approaches directed toward hospitals may be useful to promote transfusion guidelines.

Clinical significance of autologous blood transfusions in bone marrow harvest from unrelated donors.

In the Japan Marrow Donor Program (JMDP), autologous blood is collected from most unrelated bone marrow (BM) donors. We retrospectively evaluated 5772 donors who underwent BM harvest between 2010 and 2015 through the JMDP. Autologous blood was collected in 96.8% of the donors; the wastage rate was 0.6%. Allogeneic blood transfusion was not required. The mean hemoglobin (Hb) levels were 12.1 g/dL after the BM harvest (mean 891 mL) together with autologous blood transfusion (mean 596 mL). Propensity-score matching was used to adjust the backgrounds. Among donors with harvested BM of 100-400 mL, autologous blood transfusion had no impact on Hb levels or complications after BM harvest. Among donors with harvested BM of > 400 mL, more autologous blood transfusion followed by a bleeding volume of ≤ 100 mL did not confer clinical benefit to donors compared with less autologous blood transfusion followed by a bleeding volume of > 300 mL. The findings of the present study suggest that autologous blood transfusion to BM donors is excessive in terms of Hb changes and post-harvest outcomes.

Reduction in adverse transfusion reactions with increased use of washed platelet concentrates in Japan-A retrospective multicenter study.

Plasma removal by washing platelet concentrates (PCs) is effective in preventing adverse reactions to PC transfusions. The Japanese Red Cross Society (JRCS) started releasing washed PCs (WPCs) as a commercially approved blood product in September 2016. This retrospective multicenter study investigated the change in the number of transfused WPCs and the impact on the incidence of adverse reactions to PCs before and after the release. The numbers and types of transfused PCs and the adverse reactions to the PCs for a year before the start of the WPC release and for a year after the release were reported by 27 medical institutes in Japan. Transfusion information for approximately 8% of the amount of PCs supplied in Japan was analyzed during the study period. After the start of WPC release by the JRCS, the number of transfused WPCs doubled. The rate of adverse reactions to PCs decreased significantly (p = 0.0223), from 4.30% before the release to 4.05% after the release. The rates of adverse reactions to unwashed and WPCs were 4.13% and 0.84%, respectively. Allergic adverse reactions were significantly decreased after the release (3.60% before versus 3.37% after). No severe allergic reactions to WPCs were reported. The release of WPCs by the JRCS significantly reduced transfusion-related adverse reactions to PCs in Japan.

Released washed platelet concentrates are effective and safe in patients with a history of transfusion reactions.

BACKGROUND: Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This retrospective multicenter study evaluated the efficacy and safety of released washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs were prepared by washing leukoreduced apheresis PCs with the platelet additive solution, BRS-A, using automated cell processors. RESULTS: Clinical data were obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were used in 94.5% of the patients with a history of recurrent or severe transfusion reactions for preventing such reactions. Responses of RWPCs were evaluated as complete response (91.6%), partial response (8.2%), no-change (0.2%), and progression (0%) and overall response was equal across subgroups divided by patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post-transfusion were 13.5 (range, 1.9-35.4) × 109/L and 3.5 (range, -13 to 53.6) × 109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) × 109/L in patients without risk factors associated with platelet transfusion refractoriness. Transfusion reactions to RWPCs were observed in only nine transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This study demonstrated that RWPCs were effective and safe in patients with a history of transfusion reactions. Further prospective studies on efficacy together with cost-benefit analysis in RWPCs are needed.

A national survey of premedication for transfusion reactions in Japan.

BACKGROUND: Premedication before transfusion is commonly administered in clinical practice despite a lack of evidence for its efficacy. The aim of this study was to clarify the status of premedication and evaluate expert opinions regarding its use in Japanese medical institutions. METHOD: Between May and July 2016, we conducted a questionnaire survey on premedication before transfusion in 252 medical institutes that were certified by an academic society or employed transfusion experts. RESULTS: A total of 141 institutes (54.2%) responded, and hematologists (n=113) comprised the most frequent respondents. The purpose of premedication was to prevent urticaria, pruritus, and fever, and washed blood products were used for anaphylactic shock or refractory transfusion reactions before. Drugs for premedication were intravenously administered either just before or 30min before transfusion. Both inpatients and outpatients were premedicated in a similar manner, and institutional guidelines were not established. More than half of the experts recognized premedication as efficient and necessary, and premedication for previous transfusion reactions was frequently implemented, particularly for platelet transfusion or in patients with hematological diseases. Some institutions administered one or more drugs for premedication from the first transfusion. Antihistamines and hydrocortisone were the most frequently used as premedication. CONCLUSION: Our study reports the current status of premedication for transfusion in Japan. Antihistamines and hydrocortisone were most commonly used for premedication despite a lack of evidence of their use. These findings may help clarify the indications for premedication and the use of washed blood products.

[Questionnaire-based survey on chemotherapy-induced anemia].

The Japan Society of Clinical Oncology and The Japan Society of Transfusion Medicine and Cell Therapy jointly conducted a questionnaire-based survey on chemotherapy-induced anemia(CIA)in cancer patients between September and November 2010, the results of which are outlined here. For all the eight main cancer types in Japan that were analyzed(breast, lung, stomach, colorectal, liver, gynecologic, and urologic cancers and malignant lymphoma), blood transfusion was required in 1.6-24.0%(mean=7.5%)of patients who received chemotherapy, and 3.9-7.3 units(mean=5.9 units)red blood cells were transfused per patient. Approximately 146,000 units of red blood cells, accounting for 2.2%of the total annual supply of red blood cell products, was estimated to be transfused to cancer patients with CIA every year. In addition, approximately 172,000 cancer patients with CIA, accounting for 40% of patients receiving chemotherapy, were estimated to have hemoglobin(Hb)levels below 10 g/dL annually. In patients who received red blood cell transfusions, the average Hb level prior to chemotherapy was 9.5 g/dL and the average lowest Hb level after starting chemotherapy was 6.9 g/dL; these values were 11.6 g/dL and 10.4 g/dL, respectively, in patients who did not receive transfusion. Furthermore, for all cancer types, almost no red blood cell transfusions were performed in patients with an Hb level of 8.0 g/dL or higher, although many patients with an Hb level of 6.9 g/dL or lower also did not receive red blood cell transfusions. These results highlight the strict restriction of red blood cell transfusion to cancer patients with CIA. Therefore, the use of alternative therapies such as erythropoiesis-stimulating agents should be considered to improve the quality of life of cancer patients with CIA.

Questionnaire-based survey on chemotherapy-induced anemia.

A questionnaire-based survey on chemotherapy-induced anemia (CIA) in cancer patients was conducted between September and November 2010. The number of patients treated with chemotherapy, rate of blood transfusion, volume of blood transfused, severity of anemia, and factors affecting blood transfusion were analyzed according to the type of cancer, in an attempt to clarify the current status of CIA in Japan. During the survey period, among the eight types of cancer analyzed (breast, lung, stomach, colorectal, liver, gynecologic cancer, urologic cancer, and malignant lymphoma), chemotherapy was given to 5.4-13.6 % (mean 9.2 %) of patients, among whom 1.6-24.0 % (mean 7.5 %) required blood transfusion. The number of units of red blood cells transfused was 3.9-7.3 units (mean 5.9 units) per patient. According to a nationwide patient survey conducted by the Ministry of Health, Labour and Welfare, it is estimated that approximately 146,000 units of red blood cells, which account for 2.2 % of the annual total supply of red blood cell products, are transfused to cancer patients with CIA yearly. In addition, it is estimated that annually approximately 172,000 cancer patients with CIA, accounting for 40 % of patients receiving chemotherapy, have hemoglobin (Hb) levels below 10 g/dL. Possible factors affecting blood transfusion include a history of chemotherapy and radiotherapy, as well as the use of platinum agents. In patients who received red blood cell transfusions, the average Hb level prior to chemotherapy was 9.5 g/dL, and the average lowest Hb level after starting chemotherapy was 6.9 g/dL. By contrast, in patients who did not receive transfusion, these values were 11.6 and 10.4 g/dL, respectively. Furthermore, in all cancer types, almost no red blood cell transfusion was performed in patients with an Hb level of 8.0 g/dL or higher, but also many patients with an Hb level of 6.9 g/dL or lower did not receive red blood cell transfusions. There was no significant difference in the ratio of adverse events following blood transfusion in this survey compared with that in the nationwide survey. The present results demonstrate the strict restriction of red blood cell transfusion to cancer patients with CIA. Therefore, there is a need to consider the use of alternative therapies to allogeneic blood transfusion, such as erythropoiesis-stimulating agents, to increase Hb levels, and consequently improve the quality of life in cancer patients with CIA.

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: a pilot study.

BACKGROUND: A surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan. METHODS: We have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010. RESULTS: The overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics. CONCLUSION: This online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.

Can we determine depressive conditions on the basis of somatic symptoms? A cross-sectional study of depressive conditions among Japanese patients at a university hospital general medicine clinic.

OBJECTIVE: We evaluated the relationship between somatic symptoms and depressive conditions among patients visiting the general medicine clinic of a university hospital. METHODS: We distributed interview forms to 332 consecutive patients who visited our clinic for the first time between March and July 2011. Somatic symptoms were rated using a symptom checklist, and depressive conditions were evaluated using the Zung Self-Rating Depression Scale (SDS). We categorized and compared 2 groups of patients: patients with an SDS score of more than 48 (depressive group) and patients with an SDS score of less than 48 (non-depressive group). RESULTS: A total of 284 (85.5%) patients returned the forms. The SDS scores were obtained from the forms of 182 patients (64.1%). The average age of these 182 patients was 46.5±18.04 years. The mean number of checked symptoms was 4.3±3.03, and the most common symptom was general fatigue (n=106; 58.2%). The number of checked symptoms in the survey was higher in the depressive group patients than in the non-depressive group patients. Multiple logistic regression analysis indicated that general fatigue, headache, and sleeping problems were significant dependent variables which were related to depressive conditions. We defined these 3 symptoms as depression-related somatic symptoms (DRSS). On a receiver-operating characteristic curve, the optimal cutoff scores were 2 of 3 DRSS and 4 of 20 somatic symptoms. CONCLUSION: General physicians should consider possible depressive conditions when patients have 2 or more DRSS or 4 or more somatic symptoms.

Fibulin-1 and fibrinogen in human atherosclerotic lesions.

Fibulin-1 is a fibrinogen-binding blood protein and a component of many extracellular matrices (ECM) including those of blood vessels. In this study, the deposition patterns of fibulin-1 and fibrinogen were examined in human coronary artery atherosclerotic lesions excised by atherectomy from 20 patients. Fibulin-1 deposition was found to be closely overlapping with fibrinogen located within the atherosclerotic lesions and in regions containing fresh thrombi. Pronounced intracellular fibulin-1 immunostaining was apparent in lesion areas rich in macrophages and foam cells, although THP-1 macrophages and foam cells were found not to express fibulin-1. Strong ECM deposition of fibulin-1 was observed in acellular atheromatous and myxomatous regions. By contrast, fibulin-1 was present at relatively low levels in the ECM associated with smooth muscle cells within and outside of lesions and was not detected in sclerotic regions. These results reveal the pattern of fibulin-1 within human atherosclerotic lesions and highlight the potential for fibulin-1, perhaps derived from the blood and acting in conjunction with fibrinogen, to play a role in the etiology and cardiovascular disease progression, particularly with respect to thrombotic aspects of atherosclerosis.

Successful management by recombinant activated factor VII in a case of disseminated intravascular coagulopathy caused by obstetric hemorrhage.

Postpartum hemorrhage (PPH) is a life-threatening emergency in obstetrics. Although recombinant activated factor VII (rFVIIa) has become used for the treatment of some cases of massive hemorrhage, its applications in the field of obstetrics are still limited. We describe a case of successful treatment with rFVIIa for PPH due to placenta accreta. The patient was a 33-year-old woman with placental previa. Cesarean section (CS) was performed at gestational week 35. During CS, there was massive hemorrhage due to placenta accreta. After CS, disseminated intravascular coagulopathy and hypovolemic shock were diagnosed. The PPH was not controlled by transfusion therapy. On the fourth day after CS, rFVIIa (90 microg/kg x 2) was given because of the persistent PPH. Bleeding decreased and no further transfusion was required from 2 days after administration. rFVIIa was useful in the treatment of this case of obstetric hemorrhage.

Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy.

BACKGROUND: Pregnancy represents a major risk factor for deep vein thrombosis (DVT). Most coagulation/fibrinolysis markers currently utilized change during pregnancy, and therefore they cannot accurately evaluate thrombotic events in pregnancy because the rate of false positive results is high. Fibrin monomer complex (FMC) has recently become widely available for diagnosing DVT. The present study examined whether FMC is suitable for evaluating thrombotic status in pregnancy. METHODS: Concentrations of FMC and other haemostatic markers were investigated in 87 pregnant women without major complications at early, mid- or late pregnancy. FMC concentrations were also measured in 127 normal non-pregnant women, and in one woman who developed DVT after delivery. RESULTS: In normal pregnant women, FMC concentrations were unchanged during early or mid-pregnancy and slightly elevated during late pregnancy. Concentrations were within reference range in most cases, and none exceeded the cut-off value for DVT. In contrast, thrombin-antithrombin complex (TAT) and D-dimer (DD) concentrations were significantly elevated in late pregnancy, and median values exceeded reference ranges. The DVT case displayed significantly elevated FMC concentrations. CONCLUSIONS: Changes in FMC concentrations during normal pregnancy are minimal compared with other haemostatic markers. Because the rate of false positivity is lower, FMC could be a potential marker of thrombotic status in pregnancy rather than TAT and DD.

Molecular characterization of 3 factor V mutations, R2174L, V1813M, and a 5-bp deletion, that cause factor V deficiency.

We identified 3 mutations in the factor V (FV) gene (F5) associated with FV deficiency in 3 unrelated Japanese patients. Patient 1 had severe bleeding symptoms (plasma FV activity, <1%; FV antigen, 9%) and was a compound heterozygote for a novel 5-bp deletion in exon 22 and the V1813M mutation. Patient 2 had moderate bleeding symptoms (plasma FV activity, <1%; FV antigen, 4%) and was homozygous for the V1813M mutation. Patient 3 had very mild symptoms (plasma FV activity, 1%; FV antigen, 5%) and was homozygous for the novel R2174L mutation. A study of recombinant protein expression revealed that the FV coagulant-specific activities in conditioned media for the FV-R2174L and FV-V1813M mutants were reduced to approximately 40% and 28% of wild-type FV, respectively. The amounts of FV-R2174L protein and messenger RNA in the platelets of patient 3 were similar to those of healthy subjects; however, the amount of FV-V1813M protein in patient 2 was decreased. Our data suggest that the severity of the bleeding tendency in patients with FV deficiency is correlated not only with plasma FV activity but also with the amount of FV protein in the platelets.