Red Blood Cell Transfusions in Greece: Results of a Survey of Red Blood Cell Use in 2013

Objective: Greece is ranked as the second highest consumer of blood components in Europe. For an effective transfusion system and in order to reduce variability of transfusion practice by implementing evidence-based transfusion guidelines it is necessary to study and monitor blood management strategies. Our study was conducted in order to evaluate the use of red blood cell units (RBC-U) in nationwide scale mapping parameters that contribute to their proper management in Greece. Materials and Methods: The survey was conducted by the Working Committee of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology from January to December 2013. The collected data included the number, ABO/D blood group, patients’ department, and storage age of RBC-U transfused. Results: The number of RBC-U evaluated was 103,702 (17.77%) out of 583,457 RBC-U transfused in Greece in 2013. RBC-U transfused by hospital department (mean percentage) was as follows: Surgery 29.34%, Internal Medicine 29.48%, Oncology/Hematology 14.65%, Thalassemia 8.87%, Intensive Care Unit 6.55%, Nephrology 1.78%, Obstetrics/Gynecology 1.46%, Neonatal&Pediatric 0.31%, Private Hospitals 8.57%. RBC-U distribution according to ABO/D blood group was: A: 39.02%, B: 12.41%, AB: 5.16%, O: 43.41%, D+: 87.99%, D-: 12.01%. The majority of RBC-U (62.46%) was transfused in the first 15 days of storage, 25.24% at 16 to 28 days, and 12.28% at 29-42 days. Conclusion: Despite a high intercenter variability in RBC transfusions, surgical and internal medicine patients were the most common groups of patients transfused with an increasing rate for internal medicine patients. The majority of RBC-U were transfused within the first 15 days of storage, which is possibly the consequence of blood supply insufficiency leading to the direct use of fresh blood. Benchmarking transfusion activity may help to decrease the inappropriate use of blood products, reduce the cost of care, and optimize the use of the voluntary donor’s gift.


Introduction
Greece is a member of the European Union, which has established guidelines for blood donation and inspection of blood establishments, but so far no uniform rules for treatment with blood and blood products have been adopted by the European Union. Accordingly, Greek authorities and blood donor associations adhere strictly to the principle of selfsufficiency that was laid out by the Council of Europe. The only source of blood in Greece is non-remunerated blood donors. In a blood system based on voluntary donation the potential for blood shortage is an ongoing risk [1]. A number of emergency scenarios, including natural or man-made disasters, pandemic outbreaks, extremes of weather, and seasonal variations of blood donations, could contribute to extremely low blood inventory levels. It seems clear that the proportion of the population eligible to donate blood is likely to fall over the coming decades while the proportion requiring these products is likely to rise. Further attention is therefore required both to manage the supply and influence the demand for existing blood and blood products.
Greece is ranked as the second highest consumer of blood components in Europe. Blood utilization in Greece exceeds 600,000 red blood cell (RBC) units annually according to data provided by the national competent authority (Hellenic National Blood Transfusion Center). Adequate transfusion practice is essential in order to cover transfusion demands. Assessing data regarding RBC units transfused at medical institutions nationally could provide the data needed for developing plans to manage the demand and supply for blood units [2,3,4]. The aim of our study was to assess and evaluate the use of RBC units in Greece in order to identify parameters that contribute to proper RBC management, which can ensure blood sufficiency, taking into account the geographical particularities of our country, the large number of transfusion-dependent thalassemia patients, and the large number of car accident victims.

Materials and Methods
The study was conducted by the Working Committee of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology. A preprinted data collection form was used and all transfusion services in hospitals all over Greece were invited to participate in the study. The survey was conducted from January to December 2013. Data collection was prospective, using preprinted forms that were filled out monthly by the participating transfusionists. Monthly collected data included the number of RBC units transfused, the ABO/D blood group, and the departments of the patients who received the RBC units. According to storage age (SA) on the day of transfusion the RBC units were sorted into groups as SA1: 0-15 days (SA on the day of transfusion), SA2: 16-28 days, and SA3: 29-42 days [5,6]. Data regarding national RBC transfusion supplies were provided by the Hellenic National Blood Transfusion Center.
Data forms were manually entered into an electronic database (Excel 2007, Microsoft Corp., Redmond, WA, USA), which was also used to perform part of the analysis. Additional statistical analysis was performed using SAS software (version 9.3 for Windows, SAS Institute Inc., Cary, NC, USA) [7,8]. Proportion comparisons were performed via the Z-test, and mean values were compared via the t-test, the accepted significance level was p<0.05.

Results
From among the 94 services initially invited, transfusion services in 23 hospitals all over Greece accepted the invitation and were eligible to participate in the study. Twelve of those 23 hospitals are located in Athens and the remaining 11 were general hospitals located in cities outside of Athens (Agrinio, Messologgi, Kavala, Zakynthos, Kefalonia, Livadia, Trikala, Larissa, Edessa, Xanthi, Florina) ( Table 1). Thirteen of the 23 hospitals (56.52%) provided data for 12 months, 9 hospitals (39.13%) for 5-8 months, and one hospital (4.35%) for 1 month. The mean number of monthly reports from the participating blood banks was 9.2±3.5 and this showed a declining trend over the course of the year (20 reports were received in January 2013, while 15 reports were received in December 2013). It is worth noting that participating hospitals were sending their reports on a voluntary basis. In order to investigate the different policies applied in large tertiary university hospitals located in urban centers and Valsami S, et al: Red Blood Cell Transfusion in Greece peripheral, small non-university hospitals (100-300 beds), two groups were created: university urban hospitals (AH1, AH2, and AH4) and general peripheral hospitals (HOA2, HOA3, HOA4, HOA5, HOA6, HOA7, and HAO9). The number of units transfused in urban university hospitals was 44,427 and in peripheral hospitals it was 14,601. Interestingly, university hospitals consumed "fresher" blood compared to peripheral hospitals (SA1 group: 78.9% vs. 38.2%, p<0.05), and accordingly peripheral hospitals used "older" blood (SA3 group: 15.8% vs. 6.8%, p<0.05). RBC units per ABO/D blood group and SA group distribution are depicted in Table 3. The distributions among SA1, SA2, and SA3 SA groups were similar for all ABO/D blood groups. In particular, the transfusion practice applied to O RhD-negative blood units was identical to other blood groups, as 63.2% of O RhD-negative units were transfused in the first 2 weeks while the percentage

Discussion
Effective blood management is affected not only by donor deficit but also by the complexity of managing inventories of blood products and availability within hospitals and health systems. Overuse or inappropriate use of blood products is a less-recognized problem that presents significant patient safety issues [11,12]. Assessing the RBC transfusion trends in various clinical settings, especially at the national level, has evolved into a major tool for promotion and development of best practices for hemotherapy [2]. In this setting we conducted a benchmark study for RBC use across Greece.
The legal and regulatory framework governing the organization and functioning of Greek blood services reflects the transposition of EU dedicated directives. Attention at the decision-making level focused mainly on strengthening vigilance and the safety of blood supplies [13]. Blood transfusion services in Greece continue to be decentralized, are located in almost every hospital, and are responsible for the whole blood transfusion chain. Blood supplies come from voluntary non-remunerated donors (51%) and replacement donors (49%). Greece has 32 blood donors/1000 inhabitants, which is close to the median range of the EU average [1,14]. The total blood collection figure for 2013 was of 590,000 units and this proved insufficient to cover consumption at the national level, according to data Blood insufficiency in Greece is related not only to increased demands but also to poor implementation of patient blood management programs, and to the fact that central inventory   In this case, the use of fresh blood possibly highlights the problem of blood sufficiency in our country, which leads to the direct use of fresh blood. Transfusion of blood in the first 15 days of storage (SA1) was a phenomenon more pronounced in hospitals with the highest blood consumption, mainly urban university hospitals ( Figure 1). These hospitals have extended Surgical departments also treating multipletrauma patients as reference centers. However, according to the last census results of 2011, Athens contains 35% of the population of Greece [15]. This reverse percentage in relation to the population is indicative of the fact that health care services focus on the country's capital. Accordingly, increased consumption of "older" blood (SA3) takes place mainly in small hospitals, including countryside ones, with limited inventory that mostly treat chronic patients. These small hospitals often use RBC units close to the expiry date supplied by other hospitals in order to decrease time expiry losses, according to data provided by the Hellenic National Blood Transfusion Center.
Regarding the total number of RBC units transfused by hospital department and despite intercenter variability, reflecting the existing variability in transfusion practice in our country, the vast majority of RBC units i.e. 75,138 units (73.47±0.27%, 95% CI) were transfused for patients in Surgery and Internal medicine departments, including Hematology/Oncology patients. The lack of strong evidence supporting specific transfusion practices could explain the overuse of blood products in specific patient populations [16,17]. Neonates and thalassemia patients received RBCs of the younger SA group in a statistically significant higher proportion (p<0.05), which has been considered as good transfusion practice by several studies for both patient populations [3,18,19]. Blood consumption in multiple-trauma patients could not be assessed due to the establishment plan of public hospitals in Greece that does not include an independent Accident and Emergency department.
The similar distribution of ABO/D blood groups across RBC units of the three SA groups (  [2,20]. According to Table 4, depicting monthly distribution of transfusions and SA data, older blood is issued during summer. May, June, July, and August are the months of summer holidays in Greece, with an impact on RBC stocks due to the decline in blood donation. Consequently, the system reacts by providing stocked RBCs of higher SA groups (SA2 and SA3). In addition, during the summer, many tourists visit Greece. The population increase along with car accident victims results in higher blood transfusion demands. Thus, implementing more intensive voluntary blood donation campaigns could help more intensively to meet the increased demands during these months, as in other developed countries [2].

Conclusion
According to our study, and despite a high intercenter variability in RBC transfusions, surgical and internal medicine patients continue to be the most common group of patients transfused with an increasing rate for internal medicine patients. Additionally, it was revealed that the majority of RBC units were transfused within the first 15 days of storage. The applied blood transfusion trend in our country seems to follow the European practice regarding the transfusion of fresh blood in certain specific patient populations such as neonates and multi-transfused thalassemia patients. However, the increased use of fresh blood possibly reveals the problem of blood sufficiency, which leads to the direct use of fresh blood due to increased demand. The conduction of a larger survey that incorporates the determinants of patient blood management with the geographical particularities related to blood transport difficulties, hospital capacity variation, data regarding RBC wastage, and blood units supplied by other hospitals could provide more data and conclusions needed for developing and implementing an integrated evidence-based transfusion strategy and structure.

Ethics
Ethics Committee Approval: Ethics Committee of the Hellenic Society of Hematology, January 2013; Informed Consent: It was taken.