Shortage Of Blood Supply Research Articles

Blood Conservation Strategies in Adult Sickle Cell Patients on Chronic Transfusion Therapy: A Single Center Experience

▪Background: Adult sickle cell patients on chronic transfusion therapy (CTT) garnered special concern during the COVID-19 pandemic, when mass cancellation of blood drives threatened the national blood supply. In response, the American Society of Hematology proposed several strategies to decrease blood utilization, while maintaining adequate disease control for sickle cell patients on CTT. These included targeting a higher end hemoglobin S%, switching patients to simple transfusions when appropriate, and transitioning to alternative disease modifying therapies. There is little evidence to support the safety of altering exchange therapy regimens. Accordingly, at the Johns Hopkins Sickle Cell Center for Adults, a multidisciplinary team of clinicians and transfusion medicine specialists evaluated patients on a case by case basis to determine how their exchanges could be modified to accommodate for anticipated blood supply shortages. We describe our blood conservation efforts during the COVID-19 pandemic and resulting clinical outcomes for adult patients with sickle cell anemia (SCA).Methods: For inclusion in this IRB-approved retrospective study, patients received at least 7 monthly exchange transfusions between March 2019 and February 2020 and continued care through March 2021. Decisions regarding CTT were made prior to data collection. Modifications to chronic exchanges included increasing the fraction of cells remaining (FCR), decreasing the end hematocrit, or switching to a hemodilution method. Additionally, select patients transitioned to monthly simple transfusions if they were clinically stable, had a hemoglobin ≤ 7 g/dL, and had a persistently suppressed hemoglobin S% (≤ 30).We collected basic demographics, pre-exchange laboratory studies, and exchange parameters before and after each transfusion encounter in the year before (March 2019 - February 2020) and during (March 2020 - February 2021) the COVID-19 pandemic. Lastly, we recorded presentations to urgent care and the emergency department; and hospital admissions during each time period. We reported descriptive statistics for the cohort and compared outcomes using the Wilcoxon signed-rank test and Mann Whitney U test. We analyzed data using Stata/SE Version 16.1.Results: We identified 58 patients with SCA who qualified for inclusion (Table 1). Fifty-three patients remained on chronic exchange transfusions during the pandemic, and five were switched to simple transfusions. For patients who remained on chronic exchanges, most received conventional automated red cell exchange (RCE) prior to (85%) and during the pandemic (77%). Use of hemodilution increased (15% to 23% of patients). Forty-three patients experienced an increase in mean FCR (33.6 (SD 11.6) vs 37.7 (4.7), p = .00). Of those, 22 patients saw a concomitant decrease in mean end hematocrit (30.8 (1.7) vs 29.6 (1.1), p = .00). These changes resulted in a decline in the average number of units per procedure (8.6 (1.9) vs 7.3 (1.7), p = .00), which corresponded to 890 units conserved. Mean pre-transfusion hemoglobin values declined (9.4 (1.3) vs 9.2 (1.3), p = 0.01), but hemoglobin S%, reticulocyte count, and ferritin values were unchanged (p > 0.05). Acute care presentations and hospital admissions declined, which were likely spurred by concerns about COVID-19 infection (Table 2, p < 0.05).During the pandemic, three patients died, one of whom had been switched to simple transfusions. This patient experienced a consistent rise in hemoglobin S% until death. Two of the remaining patients on simple transfusions were switched back to automated RCE due to an increase in hemoglobin S% above goal (Figure 1).Conclusions: During the COVID-19 pandemic, we conserved red blood cell units through expanded use of hemodilution, higher FCR values, and switching some patients to simple transfusions. Patients who remained on exchanges maintained hemoglobin S% values near a goal of 30% without increasing iron burden. In contrast, the majority of patients who were switched to simple transfusions were unable to maintain goal hematologic parameters, and one patient died. Our data suggest that in a blood shortage crisis, changing the exchange procedure itself may be the safest means of conserving blood in a population of adult sickle cell patients; however longer follow-up is needed to ensure that these changes are safe. [Display omitted] DisclosuresLanzkron: GBT: Research Funding; Shire: Research Funding; Novo Nordisk: Consultancy; CSL Behring: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novartis: Research Funding; Imara: Research Funding; Bluebird Bio: Consultancy.

Use of donor-specific red blood cell transfusions for patients undergoing liver transplantation during the COVID-19 pandemic

Increased risks have been found for patients undergoing liver transplantation due to the blood supply shortage following the ongoing coronavirus disease 2019 (COVID-19) pandemic. Hence, exploring a method to alleviate this dilemma is urgent. This phase I, nonrandomized, prospective trial aimed to evaluate the safety and feasibility of using donor-specific red blood cell transfusion (DRBCT) as an urgent measurement to alleviate the blood supply shortage in deceased donor liver transplantation (DDLT). The outcomes of 26 patients who received DRBCT and 37 patients in the control group who only received 3rd party packed red blood cells (pRBCs) transfusion between May 2020 and January 2021 were compared. Patients receiving DRBCT did not develop transfusion-related complications, and the incidence of postoperative infection was similar to that in the control group (23.1% vs. 18.9%, P=0.688). Because the patients received the red blood cells from organ donors, the median volume of intraoperative allogeneic red blood cell transfusion from blood bank was 4.0 U (IQR 1.1-8.0 U) in the DRBCT group, which is significantly lower than that (7.5 U, IQR 4.0-10.0 U) in the control group (P=0.018). The peak aspartate aminotransferase (AST) level was significantly lower in the DRBCT group than in the control group (P=0.008) and so were the AST levels in the first two days after the operation (P=0.006 and P=0.033). DRBCT is a safe and effective procedure to lower the need for blood supply and is associated with a reduction in AST levels after transplantation. DRBCT is beneficial to patients receiving life-saving transplantation without sufficient blood supply during the COVID-19 pandemic.

Sequential Cellular Niche Plays a Crucial Role in the Generation of Enucleated Erythrocytes from Human Pluripotent Stem Cells

In vitro generation of human red blood cells (RBC) from human pluripotent stem cells (hPSCs) provides an alternative cell source for blood transfusion medicine to overcome blood supply shortages. However , the efficacy in terms of erythroblasts enucleation remains a great challenge. In this study, we develop a scalable differentiation method to generate enucleated mature erythrocytes from hPSCs through a novel monolayer differentiation procedure with sequential niche cues.The hematopoietic differentiation was initiated with induction of mesodermal development which was tracked by using a brachyury-GFP reporter system in hPSCs. We used a concerted activation of Activin/Nodal, BMP4, Wnt, VEGF, and bFGF signaling pathways to effectively promote a sequential development of early mesodermal progenitors (brachyury+KDR- cells), cardiovascular-hematopoietic committed mesodermal progenitors (brachyury+KDR+ cells), hematopoietic-endothelial progenitors (KDR+CD34+CD31+ cells), and hemogenic endothelial (HE) cells (CD34+CD31+CD144+CD73-CD188- cells). At day 6, the grape-like CD34+CD43+CD90+CD235a+CD41a+CD38-CD45- erythroid/myeloid progenitors(EMPs) began to appear and gradually bud off from the HE cells. Addition of EPO promoted erythroid cells differentiation, resulting in gradual loss of the expression of CD34, CD90 and CD41, and acquiring expression of CD235a and CD71, markers for erythrocytes. However, those erythrocytes had limited potential to develop into enucleated erythrocytes (<5%), and expressed mostly γ hemoglobin and low level of β hemoglobin.To investigate the cellular niche effect on erythroid cells differentiation of hPSCs, we cultured HE cells with OP9 stromal cells or endothelial cells transduced with the adenoviral E4ORF1 gene (E4ECs). Co-culture of HE cells with either endothelial cells or OP9 cells gave rise to significantly increased number of hematopoietic cells. To further determine the cellular niche effect on erythrocyte maturation, we cultured CD235a+CD71+ cells on OP9 cells or E4ECs. Subculture of endothelial-primed CD235a+CD71+ erythrocytes on OP9 cells gave rise to 80% enucleated erythrocytes with a high level of β hemoglobin expression, whereas subculture of OP9-primed CD235a+CD71+ erythrocytes on OP9 cells give rise to only 10% enucleated erythrocytes. It was interesting that endothelial-primed CD235a+CD71+ erythrocytes were unable to generate enucleated erythrocytes on OP9-DL1 cells that ectopically express Notch ligand Delta-like 1, suggesting that Notch signaling impaired erythroid maturation. Notably, prolonged culture of HE cells on endothelial cells reduced enucleated erythrocytes to 40% in the following erythrocytes maturation stage.In conclusion, we establishe a novel method for efficient production of enucleated erythrocytes from hPSCs. We demonstrate for the first time that sequential niche cues effectively promote erythroblasts enucleation and γ globin to β globin switch. Our method offers a novel opportunity to study erythroid development, regulation of globin switching, drug testing, and modeling of RBC diseases in vitro . DisclosuresNo relevant conflicts of interest to declare.

Impact of COVID-19 pandemic on rare diseases - A case study on thalassaemia patients in Bangladesh

ObjectivesThalassaemia is a life-threatening rare disease, which requires regular blood transfusion and medical care. The information on how thalassaemia patients are affected during the unprecedented COVID-19 crisis is scarce. This study aimed to assess the impact of the COVID-19 pandemic on the blood transfusion and healthcare access of thalassaemia patients at the community level in Bangladesh. MethodsA cross-sectional study was conducted among thalassaemia patients registered in a community-based ‘thalassaemia registry’ in Jamapur, Bangladesh. ResultsAs compared to pre-COVID-19 time, the number of blood transfusions among patients under the thalassaemia registry was significantly reduced during COVID-19 pandemic (190 units versus 81 units). In addition, the median number of red cell transfusions per patient was dropped significantly from 4 units to one unit. Over 80% of patient had no access to healthcare services at all during the early phase of the pandemic. ConclusionsEmergency response with appropriate mitigative measures must be a priority for addressing an acute shortage of blood supply in situations like COVID-19 pandemic.

Proactive strategies during a COVID-19 pandemic on regional center for blood transfusion in Oujda city and its impact on blood supply management

At the end of March 2020, the new coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus was declared a global pandemic. By mid-May, the number of confirmed cases had risen to more than 5 million and more than 300,000 deaths were reported worldwide. Morocco confirmed its first imported case of COVID-19 on March 2, 2020. As of May 31, 2020, there were 7550 confirmed cases of infection with this virus. Like many countries, this epidemic prompted the Moroccan government, as of 20 March 2020, to apply travel restrictions and suspend travel within and between cities to prevent the spread of the disease. These distancing measures have resulted in effective control of the virus. However, they also have a profound effect on the health system, relatively speaking, on blood donation and supply and the management of transfusion at the national level. In this context, on March 20, 2020, WHO provided guidance on the management of the blood supply. In addition, the National Centre for Blood Transfusion and Haematology (NCBTH) has accompanied the Regional Centers for Blood Transfusion (RCBT) of the kingdom through the implementation of a new strategy to deal with a possible shortage of blood supply. In response to such a situation, the Oujda Regional Center for Blood Transfusion (ORCBT) anticipated the development of a proactive regional strategy in collaboration with the Blood Donor Association of the Eastern Region (BDAER), and set up accompanying measures during the pandemic. The objective of this study is to describe the strategies undertaken during the COVID-19 pandemic and their impact on all transfusion activities from blood collection, delivery, and transfusion of Labile Blood Products (LBPs). To achieve our objective, we performed a comparative prospective analytical study from January 1 to May 31 of 2019 and 2020 years at the ORCBT, located in the prefecture of Oujda Angad. The results of this study showed a positive impact, to some extent, of the strategies implemented, first on blood collection and then on the center′s safety stock, which remained at the same level despite the containment circumstances. Thus, the ORCBT carried out its mission by responding to the majority of requests for LBPs that were addressed to it with a satisfaction rate of over 90% for all health facilities in the eastern region during the study period.

Physicians' Experience in Blood Supply Shortages and the Top Factors That Impact the Clinical, Economic, and Humanistic Outcomes of Myelodysplastic Syndrome (MDS) Patients in 5 European Countries

Introduction: Among patients with MDS, it is estimated that 17-82% (median 60%) are transfusion dependent (Harnan S, et al. Acta Haematol 2016;136:23-42) and require ≥ 1 unit of red blood cells (RBCs) every 8 weeks. Sufficient blood supply is essential for the administration of RBC transfusions in patients with MDS, as shortage of blood supply may create unnecessary burden, such as treatment delay, worsened quality of life, or increased healthcare utilization. To our knowledge, no studies have examined the physicians' experience associated with shortage of blood supply and RBC transfusion delays in this patient population. Physicians' perspectives on the factors that impact clinical, economic, and humanistic outcomes of patients with MDS are also not well understood. The current study investigated physicians' understanding of these topics. Methods: Prior to data collection, interviews were conducted with physicians (3 each in France, Germany, Italy, Spain, and the UK) to pre-test and revise the questionnaire, a 40-minute web-based physician survey via the M3 Global Research physician panel, for relevance and understanding. All physicians took the survey in their native language and had to have been in practice for 2-35 years, spend ≥ 75% of their time in direct patient care, and have managed ≥ 15 patients with MDS in the past 3 months. Physicians answered questions regarding adequacy of blood supply related specifically to RBC transfusions for patients with MDS. Physicians identified the top 10 factors (from a list of 32) impacting the clinical, economic, and humanistic outcomes of patients with MDS. These factors were then weighted accordingly (assigned point values summing up to 100). Results were described descriptively in proportions for categorical/ordinal data and mean (standard error [SE])/95% confidence intervals [CI]) for continuous data. Results: A total of 244 hematologist/oncologists, 124 hematologists, and 10 oncologists completed the survey in France, Germany, Italy, Spain, and the UK (n = 75 [approx.] in each country; Table). On average, physicians were in clinical practice for 14.70 years (SE 0.32), 41.3% were aged 45-54 years, and 64.3% were male. Physicians spent 88.7% (SE 0.36%) of their professional time in patient care, and had seen an average of 54.5 (SE 2.26) patients with MDS in the past 3 months. Over 65% of physicians (range 54.7 [France]-73.7% [UK]) reported that their patients with MDS encountered RBC transfusion delays due to blood supply shortage (Table). On average this impacted 9.0% (95% CI 7.6-10.4) of all patients with MDS. However, among physicians who reported delays (n = 248), 13.8% (95% CI 11.9-15.7) of patients were impacted, ranging from 11.0% (Spain) to 19.4% (Italy). Physicians (17.2%; range 9.3 [Spain]-31.6% [Italy]) reported ≥ 25% of their patients with MDS requiring transfusions experienced transfusion delay due to blood supply shortage. On average, patients experienced a 4.2-day (95% CI 3.6-4.8) delay in receiving a transfusion due to blood supply shortage, and 16.7% (95% CI 14.3-19.1) of patients required additional healthcare provider visits due to blood supply shortages. The top 10 factors reported that impact clinical, economic, and humanistic outcomes of patients with MDS included: Eastern Cooperative Oncology Group performance status (ECOG PS) (74.6%); age (66.7%); hemoglobin level (66.7%); infections (61.1%); percentage bone marrow blasts at diagnosis (60.1%); comorbidities (59.5%); platelets (56.3%); cardiovascular comorbidity (52.9%); genetic abnormalities (50.3%); and white blood cell count (48.4%). Factors that had the greatest mean impact scores were ECOG PS (8.9, 95% CI 8.1-9.8); percentage bone marrow blasts at diagnosis (8.3, 95% CI 7.3-9.2); age (7.2, 95% CI 6.5-8.0); hemoglobin level (6.8, 95% CI 6.1-7.4); and comorbidities (6.6, 95% CI 5.9-7.3). Conclusions: Two thirds of physicians reported that shortage of blood supply resulted in a delay in RBC transfusions for patients with MDS. Almost 20% reported ≥ 25% of their patients with MDS requiring transfusions experienced a transfusion delay due to blood supply issues. ECOG PS, hemoglobin level, and age were the top factors reported to impact outcomes of patients with MDS. New treatment options should be explored to help reduce the number of RBC transfusions, which may also help improve clinical, economic, and humanistic outcomes of patients with MDS. Disclosures Gupta: Bristol Myers Squibb: Consultancy, Research Funding; Kantar: Current Employment. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Constantino:Kantar: Current Employment. Grisolano:Kantar: Current Employment; Bristol Myers Squibb: Consultancy. Tang:Bristol Myers Squibb: Current Employment; Asclepius Analytics: Current Employment. Jones:Bristol Myers Squibb: Current Employment. Tang:BMS: Current Employment, Current equity holder in publicly-traded company.

A NOVEL PRE-VASCULARIZED TISSUE ENGINEERING CHAMBER SERVES AS A BIO-ARTIFICIAL PANCREAS FOR AN ATTRACTIVE SITE OF ALLOGENIC AND XENOGENEIC ISLET TRANSPLANTATION

Background: Although the sites for clinical or experimental islet transplantation have been well established, the pancreatic islet survival and function in homing locations still remain unsatisfied[1]. One of possible reasons that account for this is local hypoxia due to the shortage of blood supply[2]. Here we modified a pre-vascularized tissue engineering chamber (TEC) in vivo which facilitated the vitality and function of seeded islets by providing a microvascular network prior to transplantation. Method: A TEC filled with MatrigelTM and bFGF-2 was created and embedded in the groin of streptozotocin-induced diabetic mice. The micro-vascularization in the TEC was analyzed by histology, real-time PCR and western blotting. Three hundreds of syngeneic islets were seeded into the chamber on day 0, 14, and 28 post-chamber implantation to research the degree of pre-vascularized in the TEC. In addition, different numbers of syngenic islets (300, 200, and 100) were seeded into the chamber on day 28 post implantation to study the TEC function influenced by islets quantities. Furthermore, we explore the feasibility of TEC as a transplantation site for islet allograft and xenograft which was treated by anti-CD45RB and/or anti-CD40L (MR-1). Results and Discussion: A highly developed micro-vascularized network was established in the TEC on day 28 post implantation. The normalization of blood glucose levels of diabetic mice was negatively correlated with the time required for pre-vascularization and the number of seeded syngenic islets. The combined treatment of anti-CD45RB and MR-1 guaranteed the grafts long-term survival after allotransplantation (5/5, 100%) and xenotransplantation (16/20, 80%). Flow cytometry showed the frequency of CD4+Foxp3 Tregs and CD4+IL-4+Th2 cells significantly increased in tolegenic xenograft transplantation, compared with the decrease of CD4+IFN-γTh1 cells. Conclusion: These findings highlight that the highly developed micro-vascularized construct facilitates islet transplantation in the TEC, implicating the possibility of application as an artificial pancreas in the future.Fig. 1. (A) HE images (1st row; scale bars: 10 μm) and histology analysis (2nd and 3rd rows; scale bars: 40 μm) of pre-vascularization TECs on day 7, 14, 28, and 35. Blood vessels were marked by black arrows in HE (1st row; scale bars: 10 μm). The micro-vascularize were stained by anti-VEGF and anti-CD31, and marked by brown and black arrows seperately (2nd and 3rd rows; scale bars: 40 μm). (B)The level of VEGF mRNA was quantified. The extent of pre-vascularization confirmed a significant increase in the 28d group compared with VEGF levels in the 7d and 14d groups (p**<0.001, p***<0.001), and no significant difference between the 28d group and the 35day group (P > 0.05). Sham of inguinal adipose tissue set as control. Data was shown as the mean ± SD and representative of three separate experiments. (C) Western blot analysis showed the protein levels of VEGF at different time points in TEC.Fig. 2. The time required for the blood glucose returning to normal level (11.1mol/dl) in diabetic mice was negatively correlated with the pre-vascularization time (A) and the seeding quantity of syngeneic islets (B). (C) Non-fasting blood glucose maintained normoglycemia after syngeneic islets transplanted in the TEC of diabetic mice, and became hyperglycaemia when the TEC removed (black arrow). (D) Insulin stained donor islet in recipient TEC at 90d posttransplant (shown brown), the islet was pointed by the red arrow (Scale bars:40 μm).Txpl: Transplantation post-implantation.Fig. 3. (A) Islet allografts (Balb/c to C57BL/6) were rejected in the untreated group within 22±2.2 d. Islet allografts treated with anti-CD45RB or anti-CD40L alone were also rejected in recipients within 24±3.12 d, 26±1.74 d. Islet allografts with the dual antibody treatment of anti-CD45RB and anti-CD40L presented long-term graft survival in all recipients. The Kaplan–Meier curves were compared with the log-rank test. (B) Non-fasting blood glucose maintained normoglycemia (5/5, 80%) in the diabetic mice after allogeneic islets transplanted, and became hyperglycaemia when the TEC removed (black arrow) (C) Islet xenograft (SD rat to C57BL/6) rejected in the untreated group, treated-CD45RB group and treated-CD40L group within 13±3.1d, 16±3.12d, 18±1.74d, respectively. Islet xenografts with the dual antibody treatment of anti-CD45RB and anti-CD40L resulted in long-term graft survival in all recipients. The Kaplan–Meier curves were compared with the log-rank test. (D)Non-fasting blood glucose maintained normoglycemia (16/20, 80%) after xenogeneic islets transplanted in the diabetic mice, and showed hyperglycaemia when the TEC removed (black arrow).(E) Another 300 xenogeneic islets were re-transplanted into diabetic mice again, which were failures for the acceptance of the xenograft. Three of four diabetic mice showing that hyperglycemia was ameliorated until the TEC was removed (black arrow). (F)Insulin stained donor allograft and xenograft in recipients TEC at 90d of posttransplant (shown brown), the islets were pointed by the red arrow (Scale bars:40 μm). National Natural Science Foundation of China (nos. 81172832 and 81771723). Special Program for Sichuan Youth Science and Technology Innovation (no. 2014TD0010). Sichuan Youth Science and Technology Foundation (no. 2013JQ0020). The Health and Family Planning Commission of Sichuan Province (no. 110190).

COVID‐19 Pandemic – blood supply challenges and approaches in AATM member countries

AbstractWith the COVID‐19 outbreak, AATM took an early initiative to provide the membership instructive recommendations and informative aide mémoire. Optimizing membership support a survey was sent to 25 pandemic affected member countries, to collect challenges and approaches on blood supply and transfusion.ApproachSurvey sent to AATM country representatives. Five questions focused on in‐country blood collection and pandemic situation, diagnosis, treatment and personal protection equipment (PPE), including a snapshot question on disease magnitude; and 2 descriptive questions on challenges and responses to overcome challenges. Country classification – 2018 UNDP statistical update Human Development Indices/Indicators (HDI). Basic metric statistics.ResultsResponse rate: 92%; HDI classification: Low – 1; Medium – 9; High – 9 and Very High – 4 countries; population range: 540 544–1 380 000 000; blood collection/1000: 2·4–36·1. Ranges/1000: hospital beds, intensive care/isolation beds and ventilators respectively: 0·5–8·2; 0·019–1·8; 0·0007–1·11. All countries had quarantine facilities. Sufficient PPE: all but three countries. Testing facilities: all but three countries. All but one country listed challenges and responses. Most common challenges and approaches were, respectively, shortages in blood donors and supply (19/22), staff safety (13/22); and mass media education and awareness campaigns (21/22), staff education on safety practices and universal precautions (18/22).ConclusionHigh response from Medium and High HDI countries. Major challenges reported: effects of pandemic on blood donors and blood supply, where most countries already were suffering from shortages due to their development state. Key approaches: staff education to prevent infection; focused public awareness campaigns to convince donors to keep coming to support the nation’s blood availability during crisis.

Blood management during the COVID-19 pandemic.

The worldwide COVID-19 pandemic has required healthcare systems to implement strategies for effective healthcare delivery while managing blood supply chain disruptions and shortages created by infection-limiting practices that have reduced blood donations. At Cleveland Clinic, we have made multiple synchronous efforts: a call for increased blood collection, alignment of efforts among transfusion medicine departments (blood banks), enhanced monitoring and triage of blood product use, and increased education on patient blood management practices regarding blood utilization and anemia management. In addition, we created an algorithm to assess anemia risks in patients whose elective surgery was cancelled to optimize preoperative hemoglobin levels.

Learning from Tweets: Opportunities and Challenges to Inform Policy Making During Dengue Epidemic

Social media platforms are widely used by people to report, access, and share information during outbreaks and epidemics. Although government agencies and healthcare institutions in developed regions are increasingly relying on social media to develop epidemic forecasts and outbreak response, there is a limited understanding of how people in developing regions interact on social media during outbreaks and what useful insights this dataset could offer during public health crises. In this work, we examined 28,688 tweets to identify public health issues during dengue epidemic in Bangladesh and found several insights, such as irregularities in dengue diagnosis and treatment, shortage of blood supply for Rh negative blood groups, and high local transmission of dengue during Eid-ul-Adha, that impact disease preparedness and outbreak response. We discuss the opportunities and challenges in analyzing tweets and outline how government agencies and healthcare institutions can use social media health data to inform policy making during public health crises.

Coronavirus Threatens Blood Supply: Patient Blood Management Now!

The outbreak of the SARS-CoV-2 pandemic has led to shortage of blood supply in health-care systems around the world. During the SARS epidemic in 2002–2003 severely affected cities experienced a dramatic decrease by 90% in blood donations, which fortunately could be compensated by importing blood units from less affected regions.1 According to the national blood transfusion services, the numbers of blood donations have already dropped dramatically in the current pandemic.2 To sustain blood supply, multiple countermeasures must be pursued. Hospitals around the world have to postpone elective surgery to preserve resources and to decrease the demand for blood units. However, there are still (emergency) patients who require allogeneic blood transfusions, for example, in trauma, obstetrics, and so on. Transfusion services desperately ask for donations and highlight, that there is no evidence for blood-related transmission of SARS-CoV-2 so far. However, shortfalls are already in existence and the overall numbers of blood donations are likely to remain at a very low level. Attempts to reduce the demand on allogeneic blood units are imperative in the present situation. Therefore, the authors encourage health care workers around the world to implement patient blood management (PBM) as soon as possible. PBM is an evidence-based multimodal approach to improve patient outcome. It is based on 3 main pillars: diagnosis and treatment of anemia, minimizing (iatrogenic) blood loss, rationale (restrictive) use of blood units. In detail, PBM comprises over 100 measures and recommendations3,4 whose implementation requires a stepwise and locally adjusted process. Nevertheless, the most important components may be adopted without much effort and can be implemented even in a busy clinical environment: - Preoperative intravenous iron substitution (anemia approx. 40% due to iron deficiency) - Intraoperative tranexamic acid (eg, 1 g for 10 minutes before incision in high risk surgery or if bleeding is apparent) - Maintaining physiological conditions: normothermia, pH > 7.2, calcium >1.1 mmol/L - Cell salvage and re-transfusion of processed blood - Single-unit policy (reassessment after each blood unit) - Rational numbers of diagnostic blood samples - If close hemoglobin measurements are needed, noninvasive hemoglobin measurement - Correct coagulation anomalies as early as possible (via conventional laboratory tests or point of care testing) Adherence to at least some of these measures will significantly reduce the demand for blood units. A meta-analysis revealed that the implementation of PBM leads to an overall decrease in transfusion demand by 39% (55% in orthopedic surgery; 50% heart surgery) and results in reduced morbidity, namely acute renal failure and thrombotic events, which reduce by about 25%, respectively. Additionally, reduced mortality rates by 11%, shorter hospitalization, and even cost savings can be achieved.5 In these times, it is of utmost importance to acknowledge these findings. After all, PBM makes a virtue of necessity and must be considered imperative in view of the current crisis.

Blood Group Antigen Shielding Facilitated by Selective Cell Surface Engineering.

Production of red blood cells (RBCs) without immunogenicity of blood group antigens is of special interest in blood transfusion therapy in clinical chemistry. In this study, a selective cell surface engineering method was developed for the preparation of antigen-shielded RBCs based on molecular imprinting. Using an epitope imprinting method, biocompatible molecularly imprinted nanogels (MIgels) were prepared with a high affinity to the blood group antigens of RBCs. The antigen-shielded RBCs could avoid the agglutination caused by blood group mismatch, resulting in the antigen-shielded RBCs in efficiently substituting RBCs in case of a shortage of blood supply. Moreover, the antigen-shielded RBCs could maintain the normal physiological structure and functions of the original RBCs. We believe that the selective cell surface engineering presented in this work may offer significant benefits in specific cell protection for biomedical application.

Analysis of blood and blood components wastage in a tertiary care hospital in South India

Objectives: The aim of the study is to determine the rate and reasons for blood and blood components wastage in the blood bank of a tertiary care hospital. Background: A major challenge facing the blood bank is to supply a sufficient amount of safe blood whenever required. India fell short of 1.9 million units of blood in 2016–2017. To overcome the shortage of blood supply, performance of blood bank can be increased either by increasing the level of resources from voluntary donors and/or by reducing the wastage of blood and blood components. Materials and Methods: This is a retrospective analysis of discarded blood components data in Pondicherry Institute of Medical Sciences from January 1, 2014, to December 31, 2018. The study analyzed the various factors responsible for discarding of whole blood, red cells, platelets, fresh frozen plasma (FFP), and cryoprecipitate units. Wastage rate was calculated with a percentage of total number wastage against the total number of collection. Results: A total of 36,631 blood components were prepared from 12,615 whole blood donations during this study period. Of the total, 7,103 (19.3%) components were discarded. The most common blood component discarded were platelets 5,980 (84%) followed by FFP 669 (9.4%) and packed red cells 451 (6.3%). Blood component expiry was the common reason for discarding. Conclusion: Implementation of proper blood transfusion policy, donor screening, and training of technical staff will help to reduce the discard rate and solve the shortage of these precious elements.

Effects of Remote Ischemic Conditioning on Cerebral Hemodynamics in Ischemic Stroke.

Ischemic stroke is one of the most common cerebrovascular diseases and is the leading cause of disability all over the world. It is well known that cerebral blood flow (CBF) is disturbed or even disrupted when ischemic stroke happens. The imbalance between demand and shortage of blood supply makes ischemic stroke take place or worsen. The search for treatments that can preserve CBF, especially during the acute phase of ischemic stroke, has become a research hotspot. Animal and clinical experiments have proven that remote ischemic conditioning (RIC) is a beneficial therapeutic strategy for the treatment of ischemic stroke. However, the mechanism by which RIC affects CBF has not been fully understood. This review aims to discuss several possible mechanisms of RIC on the cerebral hemodynamics in ischemic stroke, such as the improvement of cardiac function and collateral circulation of cerebral vessels, the protection of neurovascular units, the formation of gas molecules, the effect on the function of vascular endothelial cells and the nervous system. RIC has the potential to become a therapeutic treatment to improve CBF in ischemic stroke. Future studies are needed to highlight our understanding of RIC as well as accelerate its clinical translation.

Identification of Potential Chemical Compounds Able to Trigger Enucleation of Immortalized Human Erythroid Cell Lines

Ex vivo production of functional red blood cells (RBCs) is a potential method to provide abundant RBCs which therefore is expected as a solution to improve the current shortage of blood supply in donor-dependent transfusion therapies. Immortalized human erythroid cell lines are expected to be an alternative source for ex vivo production of RBCs, as these cells are already committed to the erythroid lineage and still keep a limitless growth capacity. We have previously established immortalized erythroid cell lines derived from human UCB-derived CD34+ cells (HUDEP) and human iPS cells (HiDEP) by ectopically overexpressing human papilloma virus E6/E7 gene (Kurita et al., PLoS ONE, 2013). HUDEP/HiDEP sustain the infinite growth capacity, express erythroid specific cell surface markers (e.g. Glycophorin-A) and produce functional hemoglobin. However, in similar to erythroid cells directly differentiated from ES/iPS cells, these cells do not efficiently enucleate and easily cause cell death upon the induction of differentiation. In this study, we employed an imaging-based high throughput screening system (Cellomics ArrayScan) combined with two distinct DNA dyes (SYTO16 and SYTOXRed) to capture morphological changes of the immortalized erythroid cell lines. Among &amp;gt;1,200 chemical compounds, we identified multiple histone deacetylase (HDAC) inhibitors (HDACi) that largely increased the enucleation of HiDEP. In particular, Fluoro-SAHA and M344 achieved 9.0 fold increase in the enucleation rate. The exert of enucleation was confirmed by morphological examinations using cytospin and motional observations by time-lapse imaging. These assay finally observed that aprrox. 20 % of HiDEP cells enucleated upon Fluoro-SAHA treatment. However, we noticed that a large proportion of enucleated cells were fragile, and a similar number of enucleated cells with damaged membrane were also found. Addition of pan-caspase inhibitor, QVD-OPH, improved the viability of enucleated cells but also blocked enucleation, suggesting that HDACi-induced enucleation is also a caspase-dependent process. Gene expression profiling revealed that the Fluoro-SAHA and M344 treatment commonly induced cytoskeletal genes including kinesins, e.g. KIF3A, indicating cytoskeletal rearrangement occurred upon Fluoro-SAHA/M344 treatment. Of note, one of main erythroid-membrane components, SPTA1, was significantly down-regulated, whereas non-erythrocytic spectrin, SPTAN1, was abnormally induced. This α-spectrin switching was considered to result in the high fragility of enucleated cells. We therefore generated HiDEP cells with enhanced expression of SPTA1 using CRISPR-activation system. Activation of SPTA1 expression significantly improved viability of the enucleated cells and as the consequence 30 % of cells successfully enucleated while damaged cells were decreased to less than 10 %. Our data propose a potential method to induce enucleation of immortalized erythroid cell lines which would lead to a future large-scale ex vivo RBC production. Disclosures No relevant conflicts of interest to declare.

A distribution strategy using a two-step optimization to maximize blood services considering stochastic travel times

The blood service is a health service that utilizes human blood as basic material with humanitarian purposes, not for commercial one. Indonesian hospital ability in blood transfusions is generally still low, especially in terms of blood supply adequacy. In fact, there are still some provinces that experience excess blood supply while many other provinces experience a shortage of blood supply. The Blood Bank in Jakarta has the highest excess blood supply. Therefore, the blood can be transferred evenly from one province to another nearby province. The aim of this paper is to determine the allocation and the route of blood distribution to achieve the minimum travel times. Some variations in travel time are difficult to predict, so we take into account the stochastic properties of them. The effectiveness of blood distribution is very dependent on the accuracy of the target number of beneficiaries and the accuracy of the number of blood bags received in distribution activities. Meanwhile, the efficiency of blood bag distribution is measured by distribution routes that are directly related to transportation costs. This study uses a two-step optimization model to reach optimality. The first step is utilizing the transportation model to make sure the destination points are only the fastest to arrive. The second step is making use of the capacitated vehicle routing problem to ensure the routing is global optimal. This model successfully creates better blood demand fulfillment while minimizing transportation cost.

Cigarette Smoke Induced Lung Barrier Dysfunction, EMT, and Tissue Remodeling: A Possible Link between COPD and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide. The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes. These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease. A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer. In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent. In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression. The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death. Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks. Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer. In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer.

Exploratory analysis of beta thalassemia and aplastic anemia transcriptomes for the advancement of ex situ erythroblast proliferation and maturation.

Background & Aim Blood supply shortage is emerging as an issue worldwide, partially due to an aging and shrinking population which diminishes the healthy blood donor pool available to national blood programmes. To secure a safe and consistent supply of blood, various strategies have been explored. With development of various molecular tools, ex vivo generation of RBCs is emerging as a promising technology to alleviate the blood supply shortage issue. Although much progress has been made in the production of enucleated RBCs from stem cells, further research is required to optimize the scalability of enucleated RBC production in a culture system, with emphasis on advanced studies into proliferation and maturation stimuli for erythropoetic progenitors. Meanwhile, the contrasting stories of erythroid hyperplasic anemia and aplastic anemia presents an interesting topic to investigate the underlying mechanisms behind erythroid cell proliferation and maturation. Beta thalassemia is caused by a defective Beta globin gene that destabilizes alpha-tetrameric formation in erythroid cells and causes premature cell death. The continued stimulation of ineffective erythropoiesis leads to erythroid hyperplasic anemia. Conversely, aplastic anemia is a condition characterized by massive erythroid cell depletion in the marrow. While both conditions present anemia clinically, the cascade of events leading up to anemia is different for each case, resulting in two dissimilar marrow microenvironments. Thus, we hypothesized that through studying the differential expressional patterns of progenitors from each condition, we can determine the important mechanistic pathways underlying erythropoiesis and erythroid cell maturation. Methods, Results & Conclusion In our study, we sought to discover the differential gene expression between Beta Thalassemia and Aplastic Anemia. To that end, we obtained the transcriptomic data of erythroid progenitor cells of Beta Thalassemia and Aplastic anemia, from publicly available databases. We performed exploratory gene expressional analysis to identify differentially expressed genes in each condition. Pathway analysis was then conducted on each set of differentially expressed genes to identify significantly perturbed signalling nodes. These genes and pathways were compared against known literature on erythroid cell proliferation and maturation, to identify novel genes and pathways in our analysis. Future work will test the application of these genes in ex vivo RBC production.

REVERSE FLOW SURAL FLAP;

Background:Soft tissues injuries at foot especially at heel expose the tendons, bones and especially joints, which leads to risk of infections and necrosis. These often result from trauma (spoke wheel), tumors, systemic diseases and their wounds such as venous ulcers and diabetic foot wounds. Surgical planning of these defects remains a challenge due to shortage of local scar free tissue and reliable blood supply. The current study is conducted to observe the purposeful benefits of reverse sural artery flap to cover wounds at dorsum of foot, ankle &amp; heel.Study Design:Descriptive, experimental study.Setting: Department of Plastic &amp; Reconstructive Surgery, Dr. Ruth KM Pfau Civil Hospital Karachi.Period:January 2015 to January 2018.Material &amp; Methods:All patients who presented with wounds at heel, dorsum of foot, and exposed calcaneus or Achilles tendon were included. A peroneal based perforator identified by hand held Doppler, a superficial vein, and the sural nerve were included in the pedicle. Patients were followed during the first 6 postoperative months. Postoperative outcomes like flap congestion, tip necrosis and flap failure were noted. Results:Total of 36reverse low sural flaps were done for the soft tissue coverage of the 24 heel defects, 8 ankle defects and4 dorsum of the foot defects. Twenty eight patients were male and eight were females and age ranged from 6 to 36 years (mean 21). Partial flap failure was seen in 3 cases and complete flap failure in 2 cases. There were no serious donor site complications and all patients were satisfied with the functional and aesthetic outcome postoperatively.Conclusion:Reverse sural artery flap is very suitable in providing soft tissue coverage of the wounds of heel and dorsum of foot. Harvesting sural flap is dependable and safe as it does not ends in any major postoperative donor site morbidity.

Crossing the wide gap between positive attitude towards blood donation and its poor practice among university students: can knowledge and demographic characteristics help?!

Egypt suffers from a continuing shortage of blood supply. University students constitute a significant portion of healthy potential blood donors. Due to lack of evidence, we investigated the knowledge, attitude, and practice (KAP) of Minia University students with regard to blood donation. We conducted a cross-sectional study which included 576 randomly selected students at Minia University, Egypt aged 20–25 years. A structured questionnaire assessed the KAP, with its related factors. Logistic regression analysis was used to calculate the odds ratios for students’ KAP across different levels of sociodemographic characteristics. While 65% of the students had positive attitude towards blood donation, 53% of the students had insufficient knowledge about blood donation, and only 35% of them had donated blood before. Age and residence were not significantly associated with KAP, while donors have a multivariable-adjusted OR (95% CI) = 0.37 (0.26–0.54) for being female students versus being males. Studying public health was associated with knowledge and attitude, but not with practice of blood donation. A 1-point increment in knowledge score was associated with significantly 18 and 11% higher odds for having positive attitude and for being a donor respectively. However, the increased likelihood of donating created by having a positive attitude was insignificant. There was a gap between attitude, on one hand, and knowledge and practice, on the other hand, of Egyptian university students with regard to blood donation. Collaborations between Ministries of Health and Education to facilitate and encourage blood donation practice for students at their place of study are required.