Design of Blood Supply Chain and Application to Marmara Region in Turkey

Blood transfusion is needed due to operations, diseases or accidents. Millions of people's health depends on the success of their blood transfusion. Planning and management is required to supply blood, test against diseases, produce blood products, store t hem and transport them to hospitals. A blood supply chain network design such as Blood Donation Centers (CBM), Regional Blood Centers (RBC), Destruction Centers (DM), and hospitals are addressed. To formulate the problem, the General Algebraic Modeling System (GAMS) software was applied to the Mixed Integer Model. When the number of RBC in Marmara region decreased from 3 to 2, opening and transportation costs increased to $5.37 million. When the number of RBCs increased from 3 to 4, opening and transportation costs decreased to $3.94 million.


I. INTRODUCTION
It is estimated that a total collection of 112.5 million blood donations were made in the 180 countries during the reporting period.Of these, 100.6 million were whole blood donations and 11.9 million were apheresis donations.These donations were collected from all types of blood donors: voluntary non-remunerated, family or replacement, and paid.This estimation has taken into consideration the partial data provided by countries [1].
The Blood Donation system (BD) aiming at providing an adequate supply of blood to Transfusion Centers (TCs) and hospitals.Blood is necessary for several treatments and surgeries, and still a limited resource.The need for blood is about ten million units per year in the USA, 2.1 in Italy and 2 in Turkey; moreover, people still die in some countries because of inadequate supply of blood products.Hence, BD plays a fundamental role in healthcare systems, aiming at guaranteeing an adequate blood availability to meet the demand and save lives [2].
The human heart is a pump created from muscle tissue.It has four compartments; in upper side the right atrium and the left atrium in lower side the right ventricle and left ventricle.A special group of cells called the sinus node is located in the right atrium.Each contraction represents a heartbeat.The heart is in a systolic phase when contracted and is in a diastolic phase when it stops.It takes about a minute for the blood to circulate through the cardiovascular system and pumping oxygenated blood into the body.The sinus node provides electrical stimuli to contract heart and pump blood.The power of the heart can be calculated by multiplying the flow by pressure.Turbulent blood flow through the vessels can be heard as a soft ticking while measuring blood pressure; this sounds are known as Korotkoff sounds.Although there are 5 recognized Korotkoff sounds only 2 are normally recorded.The first sound heard indicates systolic pressure and last sound is recorded as diastolic pressure.Cardiac output is the measurement of blood flow rate from the heart through the ventricles [3].An average person's body is circulating 5 liters of blood per minute and the blood flow rate is 10 -4 m 3 /s.The pressure in the heart is approximately 10 4 Pa.It is accepted that systolic blood pressure of people is 80 mm Hg column and diastolic blood pressure is 120 mm Hg column.The 10 mm Hg column pressure is equal to 1.333 kPa.The cardiac output is 10 7 cm 3 /s.The mechanical power can be found as 1.71 W. Using efficiency value of 0.20 the chemical power is found as 8.55 W. Based on mechanical power it is seen that the human heart performs energy of 3.77 GJ during the 70 years of life span.This amount of energy is equivalent to approximately 100 liters of gasoline.
Thousands of people need a blood transfusion every day due to surgery, illness or accidents.The health of millions of people depends on the success of blood transfusion.Providing blood through donations, testing against diseases, producing and storing blood products, transporting them to the hospital and delivering them to the patient are the main activities of blood banking.These tasks need to be carefully planned, managed and controlled.To secure the supply blood a regulation published by the Ministry of Health in 2008.Turkish Red Crescent was authorized to collect blood and distribute blood products.The Turkish Red Crescent on blood services faces some problems due to insufficient blood donations and inefficient logistics system and planning decisions.Countries in the low-income and lowmiddle income group represent 2% and 22% of global donations respectively while they represent 9% and 39% of the global population.46 countries in the African Region collected approximately 5.6 million blood donation units.Although these countries are hosting about 13% of the global population they are only 4% of global donations.11 countries in the Southeast Asian Region reported collecting 15% of global blood donations but these countries represent 26% of the global population.In the European Region reported donations represent 30% of the global total but only 11% of the global population lives in the region.Blood donation system can be collected 12 hours before the Liban Ali Mohamed, Osman Yazicioglu, and Oguz Borat Design of Blood Supply Chain and Application to Marmara Region in Turkey emergence of blood donation by donating system in an electronic environment [4].For the delivery of blood to the necessary places an application has been downloaded to the mobile phones and the choice is made for the demand and distribution between the regional blood centers and hospitals [5].In spite of all the developments in the field of medicine and technology there is no substitute for blood, blood components and blood derived components.Blood is a treatment tool that is human and has no other alternative to obtain it.Today the countries that have established problems in the field of blood banking and have established an effective organization have defined blood banking activities in two stages.Donation Blood Banking is about safe, voluntary, regular conscious providing blood without waiting for a response performing laboratory procedures for donated blood, keeping blood and delivering to hospitals.Transfusion Blood Banking refers to the use of blood for patients and monitoring of the information recorded after use.Blood banking systems in developed countries working in line with their health policies can be summarized as follow: The American Red Cross meets more than 40% of the blood needs of the country processes it and distributes it to 3000 hospitals and transfusion centers throughout the country.Each year the Red Cross receives 6.5 million units of blood donation from approximately 4 million blood donors and distributes more than 9 million blood components.
German Red Cross blood transfusion services receive 3.5 million whole blood donations per year.With the donations made.80% of the country's blood needs are met and there are 2 million volunteer blood donors.Japanese Red Cross donation blood banking services are provided 7 regional blood centers.According to the blood banking system applied in the country, 3 different blood donation types are observed.The number of annual blood donations is 2 million units.High-income countries collect 47% of global donations, while their population is only 19% of the global population.Low-income and low-income middle-income countries account for 2% and 22% of global donations representing 9% and 39% of the population.In the African region 46 countries gathered approximately 5.6 million blood donations.Although these countries are hosting about 13% of the global population, they are only 4% of global donations.In the Southeast Asian Region 11 countries reported collecting 15% of global blood donations but these countries represent 26% of the global population.In the European Region, reported donations represent 30% of the global total but only 11% of the global population lives in the region.According to the reports of 180 countries 74 countries provide more than 90% of the blood through voluntary donations.Fifty seven countries provide more than 99% of the blood through voluntary donations.More than 50% of the 73 countries are provided with relatives donations.Twenty two countries reported that they still collect blood as a toll [1].
In 1957, the Turkish Red Crescent opened its first Blood Centers in Istanbul and Ankara and the country started to meet the needs of the blood through donations based on volunteerism.In the first year, the need coverage ratio which is 20%, has increased to 80%.The part that cannot be met by volunteer blood donation is mostly met by the hospital blood centers by the replacement of blood.The ratio of voluntary blood donation population in developed countries this rate is around 3.6% in Turkey amounted to 5%.The inability of the number of volunteer blood donors is an important problem for us.Turkish Red Crescent will provide enough blood to meet the needs of the whole country within the framework of a plan made by the end of 2020.Blood Component Identification and Traceability System used to determine the number of blood use in the country.In 2016, the country's need for blood was seen as 2.7 million units.In 2016, the Turkish Red Crescent met with 2141765 units of blood donation, which provided 79% of the country's blood need.In 2016, 86% of male and 14% female donors were donated by blood donors.In 2016, 2141765 units of blood donation were obtained.The demands of the cities in the Marmara region (cities; Istanbul, Edirne, Kirklareli, Tekirdag, Canakkale, Kocaeli, Yalova, Sakarya, Bilecik, Bursa, and Balikesir) are met by European RBC, Northern Marmara and Southern Marmara Region Blood Centers [6].There are three elements of blood banking studies by the Turkish Red Crescent: Regional Blood Centers, Blood Donation Centers, and Transfusion Centers.The Regional Blood Center (RBC) is the most comprehensive unit of blood banking which is established in the regions to be determined by the Ministry working in cooperation with blood donation and transfusion centers in its own region and capable of meeting the blood.The blood donation center (BDC) is a unit that takes blood from the donor and works in connection with the RBC.It is the unit which is opened by RBC in voluntary unrequited and regular donor organizations organized by RBC in the places deemed necessary for safe blood supply.Transfusion Center (TC) is the unit that does not have the power to take blood from the blood donor except for emergency cases is the unit that provides the blood or its component for the purpose of cross-comparison for transfusion and other tests required for use by patients.Volunteer citizens who want to give blood donations give blood in blood donation centers and these bloods are regularly brought to the Blood Zone.Blood All bloods brought here from donation centers are tested to produce erythrocyte plasma and platelets after testing.Blood samples from blood centers are tested and blood products are produced from the appropriate ones and blood is delivered to the transfusion centers where the need is given to patients [7].

II. BLOOD COMPONENTS AND FEATURES
Due to the fact that whole blood use is prohibited by the Ministry of Health except for emergencies.The collected bloods are divided into three components; platelets, plasma and erythrocytes.Blood is the only fluid tissue in the body.It appears to be a viscous homogeneous liquid but the microscope reveals that blood has both cellular and liquid components.Blood is a specialized type of connective tissue in which living blood cells called the formed elements are suspended in a nonliving fluid matrix called plasma.The collagen and elastic fibers typical of other connective tissues are absent from blood but dissolved fibrous proteins become visible as fibrin strands during blood clotting.Plasma is the main component of blood and is mostly composed of water.
Proteins ions nutrients and wastes are also available.The plasma the liquid component of the blood can be isolated by turning a blood tube at high speed in a centrifuge.The dense cells and platelets pass through the base of the tube to form red and white layers while the plasma remains at the top and forms a yellow layer.Plasma is about 90% water and the remaining 10% consists of ion.Protein, nutrients, waste, and dissolved gases.The ions, proteins and molecules contained in the plasma are important for maintaining the pH and the osmotic equilibrium.The main protein in human plasma is albumin.Approximately 30% of the total product demand belongs to the plasma.Plasma can be stored at -25°C for up to 36 months.The plasma consists of approximately 55% of the blood.Erythrocytes specialized cells that circulate in the body and give oxygen to tissues.In humans red blood cells are small and biconvex (the finest in the center only 7 -8 m in size) and do not contain mitochondria or nuclei when they mature.These properties allow red blood cells to effectively perform the oxygen transport task.The small-size and double-sided shape creates an additional area for hemoglobin.a key protein used in oxygen transport while increasing the volume ratio of the surface area that improves gas exchange.Lack of mitochondria prevents red blood cells from using any of the oxygen they carry.Thus the amount of O2 transmitted to the tissues of the body is maximized.Red blood cells take oxygen in the lungs and release this oxygen into the surrounding tissues as they circulate the body.Red blood cells also play an important role in transporting a waste product carbon dioxide from the tissues to the lungs.Some of the carbon dioxide binds directly to hemoglobin and red blood cells also carry an enzyme that converts carbon dioxide to bicarbonate.The bicarbonate is dissolved in plasma and transported to the lungs where it is converted to carbon dioxide and released.The average life of red blood cells is 120 days.Old or damaged red blood cells are broken down in the liver and spleen and new ones are produced in the bone marrow.Red blood cell production is controlled by the erythropoietin hormone released by the kidneys in response to low oxygen levels.This negative feedback loop allows the number of red blood cells in the body to remain relatively constant over time.Red blood cells comprise about 45 percent of the blood.Platelets also called platelets are parts of the blood involved in blood clotting.They are produced by breaking up large cells called megakaryocytes.Each one is shredded while receiving 2000-3000 platelets.The platelets are roughly disc-shaped and have diameters less than 2-4 m.When a lining of a blood vessel is damaged platelets form a sticky plug and are pulled into the wound area.Platelets not only attract other platelets but also make them sticky.It is the conversion of fibrinogen.a water-soluble protein found in blood plasma into fibrinogen-insoluble filamentous fibrin.Fibrin forms the threads that strengthen the platelet plug and creates a clot that prevents further blood loss.The platelet can be stored at 20-24ºC for up to five days with continuous shaking.White blood cells also called leukocytes are less common than red blood cells and constitute less than 1% of blood cells.Their role is also very different from red blood cells: they primarily participate in immune responses to recognize and neutralize invaders such as bacteria and viruses.White blood cells are larger than red blood cells and.unlike the red blood cells they have a normal core and mitochondria.White blood cells are found in five main types; neutrophils, eosinophils, basophils, monocytes, and lymphocytes [8].

III. TRANSPORTS AND STORAGE OF BLOOD AND BLOOD COMPONENTS
There are eight blood components as ES, CRYO, APTT-P, P-ES, TK, APTT, TDP, and HPLT used by Turkish Red Crescent in 2017 [6].Fresh frozen plasma, cryoprecipitate reduced plasma, and cryoprecipitate can be stored at temperatures between 18 o C and -25 o C for up to 3 months and it can be stored up to 36 months at temperature below -25°C (Fig. 1).These conditions should be kept as close as possible during transport.If the storage temperature does not change during defrost, no-frost freezers can be used.The temperature in the freezer should be recorded continuously.The alarm system must be both visually and audibly alerted and checked regularly.Separate areas should be identified for different types of components and each area should be clearly marked to prevent errors.All data regarding the preparation, storage and transport of plasma components should be recorded.All process and technology (software and equipment) should be documented.It is kept as close as possible to the recommended storage temperature during transport and stored under the recommended conditions if it will not be used immediately at the point of treatment [9,10].
If transfusion necessary in any patient should be ensured about right blood, right patient, right time, and right place.Following principles underpin safe and effective transfusion practice [9]: 1 Transfusion should only be used when the benefits outweigh the risks and there are no appropriate alternatives.To prevent sensitisation and the risk of HDFN, RhD negative or Kell (K) negative girls and women of childbearing potential should not be transfused with RhD or K positive erythrocytes except in an emergency.Use of automated analysers, linked to laboratory information systems, for blood grouping and antibody screening reduces human error and is essential for the issuing of blood by electronic selection or remote issue.When electronic issue is not appropriate and in procedures with a high probability of requiring transfusion a maximum surgical blood ordering schedule (MSBOS) should be agreed between the surgical team and transfusion laboratory.There are more than 300 human blood groups but only a minority cause clinically significant transfusion reactions.The two most important in clinical practice are the ABO and Rh systems [9].The use of automated analyzers associated with laboratory information systems blood grouping, antibody screening and blood selection by electronic selection or remote notification reduce human errors.It is to be agreed between the surgical team and the transfusion laboratory that the maximum number of surgical blood sets is required for transfusion and where the electronic issue is not suitable and the methods are highly probable.There are more than three hundred human blood groups, but only a small proportion of them cause clinically significant transfusion reactions.The second system is called the Rhesus System and is classified as Rhesus Positive (+) and Rhesus Negative (-).
Table II shows the compatibility of the blood group.A person with an AB + blood group can take blood from all the important blood groups.People with an o-blood group can only take blood from donors with the same blood group [9,12].Giving blood enables many people to maintain their normal healthy lives.Thousands of patients have thousands of blood transfusions each year in Irish hospitals.Only 3% of the Irish population gives blood and provides blood to more than 4 million people.3000 blood donors are needed every week in Ireland.One in four needs blood transfusions at some point in their lives.The most common blood type in Ireland is O positive and the rarest blood group is AB negative.The blood group distribution of Irish blood donors is given in Table IV [12].Blood group A+ has the highest frequency in Turkey and O+ has the highest frequency in Ireland.

IV. BLOOD SUPPLY CHAIN NETWORK DESIGN
In today's world supply chains are more complex than ever.Consumers' demand for new products and the still critical economic situation require companies and organizations to be more innovative and more cost-effective in their procurement and production as well as in their delivery.Nevertheless despite numerous successes the supply chain management discipline still cannot adequately address many practical real-world challenges [13].Some researchers recommend the following in blood transfusion: Observations such as pulse, blood pressure, temperature, and respiratory rate should be undertaken and documented for every unit transfused.Minimum monitoring of the patient should include the following: Pre-transfusion observations taken and recorded no more than 60 min before the starting of the component transfusion.Observations 15 min after the starting of each unit and post-transfusion observations taken and recorded not more than 60 min after the end of the component transfusion [17].
There are 17 fixed blood donation centers (BDC) and 40 mobile donation points in 11 provinces in the Marmara region.There are three regional blood centers (RBC) in Kartal, Istanbul on the Asian side of Istanbul and in Bagcilar, and Bursa on the European side of Istanbul.In this region, there are 137 public hospitals and polyclinics as demand points.It is the essence of the problem that hospitals are late in responding to demand or that patients are victims because of excessive cost when demand is met or demand cannot be met.The problems caused by the lack of this system are +described in Figure 2 [18].The cost of transport between RBC opening, destruction center, BDC and RBC is taken into consideration and the cost between RBC and destruction center is taken into consideration and the objective function that minimizes costs can be established as follows: The constraints used in optimization are given in Table V. Hospital bed capacities, blood requirement per bed per week and the distances (km) between hospitals and the regional blood centers (RBC) are given in Table VI.The amount of blood collected for in 2016 in BDCs in Marmara region and distances between blood donation centers=BDC and regional blood centers=RBC in (km) are given in Table VII.The number of blood donations in Marmara Region for year 2016 is given in Table VIII.The amount of blood products; erythrocyte, plasma, and platelet destroyed in 2016 in the Turkish Red Crescent Marmara Region is given in Table IX [6].Capacity and cost analysis for new distribution centers are given in Table X with some changes [7].The model was solved using GAMS 23.5 software.According to the obtained results the amounts of blood sent from BDC i to RBC j are given in Table XI.The amount of blood delivered to any k hospital from any RBC j was obtained as in Table XII.V. CONCLUSION In this study, a blood supply chain network design such as Blood Donation Centers (BDC), Regional Blood Centers (RBC), Destruction Centers (DC), and hospitals (H) were considered.According to the GAMS software version 23.5, the Mixed Integer Model was found to be suitable and formulated for the problem.
When the number of RBCs in Marmara region were reduced from 3 to 2 the opening and transportation costs increased to $5.37 million.When the number of BDCs was increased from 3 to 4 the opening and transportation costs fell to $3.94 million if the existing 3 RBCs remain the same the opening and transportation costs will increase to $4.76 million.
It is possible to add 1 more RBC to the existing RBCs in the region and add 1 destruction center to the destruction centers thus minimizing the distance between RBCs and hospitals and eliminating the blood products that cannot be used in the existing supply chain without damaging the environment and human health.With the proposed model it has been seen that blood donation centers have access to regional blood centers and transportation costs from regional blood centers to hospitals can be minimized.

Symbols and Abbreviations List
BDC: Blood Donation Center RBC: Regional Blood Center DC: Destruction Center i: BDC index j: indicates the potential RBC approved by the decision maker.k: integrated cluster index of potential RBC and hospitals.
m: Indicates the index of DC.The parameters used are given below.bij: Distance between potential RBC j and BDC i djk: Distance between RBC and hospitals q: Transportation cost per kilometer ($/km) fj: Opening cost for j RBC ($/year) am: DC opening cost rjm: Distance between RBC j and DC m gjm: The amount to be transported between RBC j and DC m (unit) hjk: The amount to be transported between RBC j and hospital k (unit) vij: The amount to be moved between BDC i and RBC j (units) Uk: Hospital demands Ti: The sum of the amount of blood collected for the products kapj: Capacity of RBC's Wm: Capacity of DC α: destruction rate (5%) Decision Variables are as follows:

Fig. 1 .
Fig. 1.Blood components and production of blood derivatives

Fig. 2 .
Fig. 2. Design of network diagram (see Symbols and Abbreviations List) 6 Results of laboratory tests are not the sole deciding factor for transfusion.3Transfusiondecisionsshould be based on clinical assessment underpinned by evidence-based clinical guidelines.4Notallanemic patients need transfusion; there is no universal 'transfusion trigger'.5Discussthe risks, benefits and alternatives to transfusion with the patient and gain their consent.6Thereason for transfusion should be documented in the patient's clinical record.7 Timely provision of blood component support in major haemorrhage can improve outcomegood communication and team work are essential.8 Failure to check patient identity can be fatal.Patients must wear an ID band with name, date of birth, and unique ID number.Confirm identity at every stage of the transfusion process.Patient identifiers on the ID band and blood pack must be identical.Any discrepancy transfusion not been applied.
9The patient must be monitored during the transfusion.10 Education and training underpin safe transfusion practice.ABO-incompatible red cell transfusion is often fatal and its prevention is the most important step in clinical transfusion practice.Alloantibodies produced by exposure to blood of a different group by transfusion or pregnancy can cause transfusion reactions, haemolytic disease of the fetus and newborn (HDFN) or problems in selecting blood for regularly transfused patients.
Blood group antigens are molecules on the surface of red blood cells.Some like ABO groups are also found in platelets and other tissues of the body.For most blood groups, genes have been identified, and tests based on this technology are increasingly undergoing clinical practice.
The two most important factors in clinical practice are ABO and Rh systems.orbloodtransfusion incompatibility.Blood plasma antibodies in plasma are shown by indirect antiglobulin test (The Indirect Antiglobulin Test.IAT).Nearly all clinically important red cell antibodies can be detected by an indirect antiglobulin assay (IAT) antibody screening performed at 37°C.There are four main blood types: A, B, AB, and O.All normal individuals have antibodies to A or B antigens that are not present in their erythrocytes (TableI).The frequency of ABO groups differs in different ethnic populations and should be taken into consideration when receiving these representative blood donor panels.For example people of Asian descent have a higher B group than white Europeans.Those blood group individuals are sometimes known as universal donors because they do not have A or B antigens in their erythrocytes.However plasmids contain anti-A and anti-B if present in high titration and some has the potential to hemolysis erythrocytes of non-O receptors.

TABLE I :
THE ARRANGEMENT OF CHANNELS DISTRIBUTION OF ABO

TABLE II :
BLOOD GROUP COMPATIBILITY [6] most common blood group is Rh positive in Turkey, the most rare blood group AB Rh negative.The 37% of Turkish people have A-positive blood group and 1% of the ABnegative blood group.According to the Turkish Red Crescent data, blood group distribution of blood donors in 2016 is given in TableIII[6].In the world the most common blood group is O-positive, accounting for about 46% of the world's population.

TABLE IV :
FREQUENCY OF BLOOD GROUP DISTRIBUTION IN IRELAND

TABLE V :
CONSTRAINTS AND DESCRIPTIONS

TABLE VII :
BLOOD DONATION NUMBER IN MARMARA REGION (UNIT) AND DISTANCES BETWEEN BLOOD DONATION CENTERS=BDC AND REGIONAL BLOOD CENTERS=RBC, (KM).

TABLE VIII :
NUMBER OF MONTHLY BLOOD DONATIONS FOR BDC'S IN MARMARA REGION (UNIT)

TABLE IX :
AMOUNT OF BLOOD DISCHARGED (UNIT)

TABLE X :
CAPACITY AND COST ($) ANALYSIS FOR THE NEW RBC CENTER.U=UNIT

TABLE XI :
THE AMOUNT OF BLOOD (UNITS) SENT FROM BDC I TO RBC J

TABLE XII :
THE ARRANGEMENT OF CHANNELS THE AMOUNT OF BLOOD SENT TO THE HOSPITAL K FROM I RBC (UNIT)