Blood Contamination, Transfusion And Donation

Before the 1990s, FVIII was obtained from whole blood donations (Figure 1), then transfused into haemophilia patients. Blood transfusions began in 1818 when James Blundell, an English physician, performed a human-to-human blood transfusion. Although the patient subsequently died, Blundell was committed to achieving a successful blood transfusion. Throughout the early 1800s, he experimented with a series of patients, of which, over half survived. This remarkable achievement may have been due to luck, as no scientific understanding relating to blood groups and their compatibility were yet discovered. It was not until the twentieth century that Viennese scientist, Karl Landsteiner, discovered the reactivity of isoagglutinin’s (antibodies causing clumping of red blood cells) in the blood, with red blood cells of other test subjects. This discovery led Landsteiner to identify the four main blood groups, A, B, AB and O (Alter and Klein, 2008)

Blood transfusion changed in 1940, when Dr Edwin Cohn, a protein chemist based at Harvard University, developed a technique to separate the various fractions of plasma. One fraction that proved especially useful, was Albumin, which was used in treating soldiers during World War 2 (WW2) who had suffered severe blood loss. Albumin kept blood vessels dilated, maintaining oncotic pressure and blood flow to the damaged areas. Also, unlike whole blood, which had to be used almost immediately after collection, Albumin could be stored for long periods before use (Learoyd, 2012). Throughout the 1950s and early 1960s, haemophiliacs were treated with either whole blood or fresh plasma. However, such products lacked sufficient FVIII to successfully stop serious bleeding. Consequently, patients with severe haemophilia died prematurely, most commonly from brain haemorrhages and post-surgery bleeds (Morfini, 2017). In 1965, American scientist Judith Pool utilized the Cohn fractionation method in the discovery of cryoprecipitate. After freezing plasma and then allowing it to slowly thaw, Dr Pool identified a thick, insoluble residue of clotting FVIII remained (Bevan, 2009). This residue, termed cryoprecipitate, was found to have 30% more clotting power than fresh frozen plasma (Philip et al., 2014). Cryoprecipitate was instrumental to the research conducted by American scientists, Brinkhous and Shanbrom in 1968. They wanted to produce a product that could be stored for even longer and administered at home; by dissolving cryoprecipitate further, then treating it with chemicals, Brinkhous and Shanbrom were left with a crystalline powder of concentrated clotting FVIII (Schmidt, 1999). This new purified blood product, termed FVIII concentrate, was freeze-dried during processing to prolong expiry and was used predominantly for the treatment of Haemophilia (Krever, 1997). However, one disadvantage that arises through the manufacture of FVIII concentrates, is key to the events discussed throughout this report. Unlike cryoprecipitate, where the risk of viral transmission is relatively low – as each bag is made from one or two donations -FVIII concentrates are prepared from pools of blood from thousands of donors; significantly increasing the risk of contracting viral diseases such as Hepatitis and human immunodeficiency virus (HIV) (Craske, Dilling and Stern, 1975).

By the 1970s, fractionators in the United States (US) had begun research into creating an ‘inactivation’ method that would reduce the risk of transmission of Hepatitis B (HepB) and the virus causing AIDS. Towards the end of 1970, one of the most promising methods of ‘inactivation’ was heat-treatment of factor concentrates. During heat treatment, factor concentrates are heated at ~70 degrees for up to 72 hours. The purpose of this method is to inactivate the virus, such that, it can no longer function and cause infection (McGrath et al., 1985). Despite commercial fractionators spending significant resources on developing heat-treatment of factor concentrates throughout the 1970s, significant strides in producing a commercially available product, only began in the early 1980s. The first heat-treated FVIII product was introduced in the United Kingdom (UK) in 1984 (Penroseinquiry.org.uk, 2015).

During the mid-1970s, the UK health system struggled to manage the increasing demand of FVIII concentrates. This led commercial fractionators to obtain licences in the UK permitting the market of FVIII concentrates sourced from paid US donors. By the 1980s, FVIII concentrates had become a profitable business for commercial fractionators, who were distributing their products to many western countries (Hagen, 1982). Almost all western European countries faced difficulties in meeting the blood product demands of their haemophilia populations; many national governments agreeing that the importation of commercial FVIII concentrates from America, was the most effective solution. UK organisations went one step further to ensure blood product demand was met, even in the case of emergencies. They entered into what was known as “short supply agreements” with American Hospitals and blood banks, where supplies of recovered plasma could be sent over at short notice. In addition, plasma was bought from plasma brokers through what known as the ‘international spot market’, where goods could be delivered almost immediately when demands unexpectedly surged. (Krever, 1997). Donors who provided recovered plasma obtained from blood banks and hospitals, were voluntary, non-remunerated individuals. Whereas, source plasma was usually collected by commercial fractionators from numerous donor populations, including prisons, borstal institutions, poor neighbourhoods and universities. Prisoners and homosexual men were considered to be a valuable source of plasma, as donors usually had a high count of HepB antibodies. For this reason, they were integral during the manufacture of the HepB vaccine (Leveton, Sox and Stoto, 1996). As presented later in this report, such groups were found to be at high risk of transmitting HIV when donating blood through the 1980s.

In early 1984, the work of Dr. Robert Gallo, an American biomedical researcher, led to the discovery of the infectious agent responsible for acquired immune deficiency syndrome (AIDS). With Gallo’s research, a test for HIV was developed in late-1984 to detect the virus in blood. The introduction of HIV testing was adopted by commercial fractionators, blood banks and national transfusion services in most Western countries (such as Ireland, USA and England) by 1985 (Schmidt, 2000).

It was found that HIV attacks the body’s immune system, specifically CD4+ cells (T helper lymphocytes), which help to fight off infections. Without a host cell, HIV cannot grow or reproduce. Rather, the virus fuses with CD4+ cells, taking control of DNA replication to rapidly multiply (Avert, 2017). If untreated, HIV continues to reduce CD4+ count, causing patients to become more susceptible to other infections. A weakened immune system to fight off infection indicates that a patient had AIDS, the last stage of HIV infection (Centers for Disease Control and Prevention, 2019). In 1983, it was recognised that certain groups were at higher risk of contracting AIDS than others. This includes the “four-H club”, as termed by the media: Haemophiliacs, Homosexuals, Heroin users and Haitians (Healthline, 2003). Many of these groups are also at risk of Hepatitis, an inflammatory condition of the liver most commonly caused by 5 main hepatitis viruses, type – A, B, C, D and E. Hepatitis A and E are usually caused through the ingestion of contaminated food or water. Hepatitis D infection occurs only in patients already infected with Hepatitis B. Throughout this report, the significance of Hepatitis B and C during the blood contamination period will be discussed. Both viruses are usually contracted as a result of parenteral contact with infected body fluids such as blood plasma (World Health Organization, 2019).

Once HIV testing became available in 1985, it was found that individuals suffering from haemophilia and other blood disorders such as anaemia, blood cancer and sickle cell disease had received contaminated blood products. Ultimately, patients became positive for blood-borne viruses such as HIV and Hepatitis. (Brecher and Hay, 2005) Statistics for the UK haemophilia population indicated that over 30% had been infected with HIV; for those with severe haemophilia, who were using commercial factor concentrates more regularly, this infection rate was much higher at 75% (Rizza, Spooner and Giangrande, 2008). Haemophilia doctors were professionally committed to providing their patients with the treatment option believed to be most effective. As such, many continued to prescribe contaminated factor concentrates throughout the early 1980s; scientists were unable to produce adequate evidence pushing for the return to earlier treatment methods such as cryoprecipitate, during the time when HIV/AIDS emerged as a risk (Crane and Kaplan, 1973). Figure 2 gives a summary of the key events that have been outlined in this chapter and those that follow.

The Peculiarities Of Blood Clotting Process

The blood is a fluid in human body and it is a part of the cardiovascular system, it consists of 55% of plasma and 45% of blood cells which transports oxygen, nutrients, and hormones to our cells and eliminates metabolic wastes from cells such as Co2 and delivers it to the appropriate organ for elimination and excretion, it also helps the body to fight against infections and diseases. The majority of the blood plasma consists of water, it also contains nutrients, metabolites, salts, hormones and plasma proteins, one of the most important protein in the coagulation process is a plasma protein called fibrinogen that binds to the platelets and form the clot, in addition to fibrinogen, many more clotting proteins are present in the plasma in form inactive precursors and can be activated by cleavage.

Blood cells are divided into 3 types:

  1. Erythrocytes: Are biconcave shaped cells that contain hemoglobin and lack nucleus and mitochondria when they mature, as a result they are very efficient at transporting oxygen and nutrients to cells and eliminating the waste materials from them.
  2. Leukocytes: Compared to Erythrocytes, Leukocytes are much larger complete cells with a nucleus and mitochondria, their main function is to provides the body’s specific immune response by secreting cytokines and activating other specialized leukocytes when a pathogen enters the body.
  3. Thrombocytes: are specialized disc like cells that aid in intravascular clotting by forming a plug at the site of vascular damage or secreting regulators of the clotting process and vascular repair, like erythrocytes, Thrombocytes also lack nucleus, they originate from budding of the cytoplasm of Multinucleated cells residing in the bone marrow known as Megakaryocytes. platelets contain 3 types of granules which are secreted during the clotting process, these granules are:
  • A. Electron dense granule
  • B. α – granule
  • C. Lysosomal granule

Clotting factors are arguably the most essential components of hemostasis. Hemostasis is the body’s physiologic response to vascular endothelial injury, which results in a series of processes that attempt to retain blood within the vascular system through the formation of a clot. Hemostasis can be further divided into primary and secondary hemostasis. Primary hemostasis, which results in the formation of a soft platelet plug, involves vasoconstriction, platelet adhesion, platelet activation, and platelet aggregation. Secondary hemostasis is primarily defined as the formation of fibrinogen into fibrin, which ultimately evolves the soft platelet plug into a hard, insoluble fibrin clot. Within primary and secondary hemostasis, 3 coagulation pathways exist: intrinsic, extrinsic, and common. The intrinsic pathway responds to spontaneous, internal damage of the vascular endothelium whereas the extrinsic pathway becomes activated secondary to external trauma. Both intrinsic and extrinsic pathways meet at a shared point to continue coagulation, the common pathway.

The Start of Coagulation Process

When a blood vessel is damaged, a series of reaction start to take place at the site of the damage that starts with vessel constriction and ends with the formation of the mechanical clot, it consists of these steps:

1. Vascular spasm

The first step is vascular spasm in which the damaged endothelium cells secret a chemical called endothelin that causes the smooth muscles surrounding the muscle to contract, decreasing the diameter of the blood vessels and ensuring minimal blood loss. The smooth muscles can also contract as a result of myogenic mechanism due to the direct contact between the muscle and the damaged vessel.

2. Platelet plug formation

Next, the damaged cells release collagen, protein called von Willebrand factor (vWF), and other materials, these released materials bind to a glycoprotein called GpIb found on the cell membranes of the platelets, activating them changing its shape from disc shaped to spherical, this binding allows the adhesion of the nearby platelets to the damaged site. When a platelet binds to a vWF, it releases some of the contents of its dense granules and α granules such as ADP, Thromboxane A2 and serotonin, ADP and Thromboxane A2 stimulate other platelets to bind to each other through another glycoprotein known as GpIIb-IIIa making the platelet plot larger and denser. Thromboxane A2 also works with serotonin to enhance the vascular spasm effect by contracting the smooth muscles and narrowing the vessel.

3. Coagulation

Activation of clot formation occurs through interlocking pathways, termed the intrinsic and extrinsic pathways. The intrinsic pathway starts when Factor XI is activated by thrombin and changed to XIa, which then activates Factor IX and changes it to IXa, then Factor VIII is changed to VIIIa by thrombin. The combination of Factor IXa and VIIIa activates Factor X to Xa. From this point the pathway is known as the common pathway as it is common between both the intrinsic and extrinsic pathway. Thrombin changes Factor V to Va, Factor Xa and Va together activates the zymogene prothrombin (Factor II) and changes it to thrombin (Factor IIa), this thrombin is used to activate previous Factors in the reaction and to activate the soluble fibrinogen (Factor I) by changing it to the insoluble fibrin (Factor Ia) which is also known as a soft clot. Th final step in the coagulation process is changing the soft clot fibrin to the hard clot cross linked fibrin, this occurs when Factor XIII is changed to XIIIa by thrombin, this Factor XIIIa then Cross links the fibrin molecules, these cross linked fibrin molecules ensures that the platelet aggregation at the damaged site wont break off to cause embolism. Most of these reactions in the cascade also require calcium, phospholipid membranes and platelet factors in order to occur.

The extrinsic pathway is much shorter than the intrinsic pathway, it is activated when the tissue factor is released into the blood by the damaged cells, these tissue factors along with PL and Ca change Factor VII to VIIa, then the activated Factor VIIa changes Factor X to Xa, from this point onwards the common pathway occurs. As we can see the extrinsic pathway can activate Factor X sooner and by a smaller number of reactions than the intrinsic pathway. The hemostatic plug formed at the end of coagulation release chemicals such ad PDGF and VEGF to help regenerate and repair the blood vessels and the surrounding smooth muscle and connective tissue.

Note that thrombin also acts as a positive feedback to the previous steps of the reaction thereby increasing the rate of the reaction as time passes.

Fibrinolysis

After successful formation of the plug, further developing of the plug must be prevented, this is accomplished by switching off blood coagulation and turning on fibrinolysis, the enzymatic breakdown of fibrinolysis is accomplished by a protein called plasmin, which exists in the blood in an inactive form plasminogen, this zymogen naturally has a high affinity to fibrin and it is activated at an efficient rate at the surface of the plug by proteins known as Plasminogen activators. Activated protein C (APC), which is an inhibitor of the blood coagulation cascade, also stimulates the release of Plasminogen activators from the damaged tissues, and simultaneously inactivates an inhibitor of plasminogen activator, PAI-1.

Plasminogen can be activated by either tissue plasminogen activator (tPA) or single-chain urokinase (U-PA). PAI-1 blocks tPA action. Streptokinase binding to plasminogen allows autocatalysis to form plasmin. Circulating α2-antiplasmin blocks the activity of any soluble plasmin that may be in the blood.

Regulators of the blood clotting cascade

Many regulators participate in this cascade reaction, either by initiating or inhibiting the reactions in the process, the main regulators of this cascade include:

1. Thrombin

Thrombin has both feedback amplification and feedback inhibition. The amplification part (also known as prothrombic effect) is when thrombin stimulates its own production by activating Factor XI, VIII, V, thus speeding up its own production rate. Thrombin also promotes clot formation by activating platelet aggregation, stimulating the release of factor VIII from vWF and changing factor XIII to factor XIIIa.

The inhibitory effect of thrombin (also known as antithrombic effect) happens when thrombin binds to the cell receptors called thrombomodulin on the surface of endothelial cells, Thrombomodulin diminishes the clotting functions by forming a complex called thrombin thrombomodulin complex (TTC), this complex activates protein C and S, which has anticoagulant effects.

2. Protein C and S

Protein C and its cofactor protein S are vitamin K dependent regulators of the coagulation process. They are synthesized by the liver in a process called γ-carboxylation, it inhibits the process by inhibiting Factor V and VIII.

After activation by TTC, protein C and S form a complex together, then this activated protein C (APC) suppresses coagulation by destroying Factor Va and VIIIa. APC also stimulates cells to to increase the secretion of prostaglandin I2 (PGI2), which reduces platelet aggregation.

3. Serpins

Serpins (Serine protease inhibitors) are small protein inhibitors that exist in high concentrations in the blood and tissues. These inhibitors each contain an active site that match the shape of a serine protease, thus acts as a trap for that specific protease. An example of these serpins include antithrombin III. Each molecule of antithrombin III binds and inactivates a molecule of thrombin in an irreversible reaction, its can also inhibit Factor XIIIa, XIa, IXa, and Xa.

4.Thromboresistance of vascular Endothelium

Normal endothelial cells are inhibitors of the coagulation process, they are negatively charged so they naturally repel platelets which are also negatively charged. Endothelial secret many powerful inhibitors such as PGI2 and nitric oxide that inhibit platelet aggregation. Endothelial cells also secret powerful inhibitors to thrombin and heparan sulfate. Heparan Sulfate is a glycosaminoglycan that promote the effect of antithrombin III. These actions by intact endothelium cells makes them a regulator in the coagulation process.

5. Plasmin

As we noted earlier, plasmin inhibits the cascade process by breaking down and degrading the fibrin mesh that surrounds the platelet aggregation.

Effects of drugs on the coagulation process. Numerous drugs effect the coagulation process, these drugs are classified intro 3 types:

1. The heparins

The heparins are activators of antithrombin III, which is an inhibitor to thrombin and some of the coagulation factors. Two type of heparins exist, High molecular weight (HMW) and low molecular weight (LMW). The difference between these two types of heparins are that LMW heparins have more specific interactions with parts of the coagulation process and are much easier to monitor on patients than the HMW heparins, which have more nonspecific interactions in the body such as binding to the plasma proteins and cell surfaces. Heparin is used to treat or prevent clots in conditions where there is a high risk of clot formation and thromboembolism.

2. Vitamin K antagonists.

Drugs such as Warfarin, Dicoumarol and phenindione are Vitamin K antagonists, meaning they oppose Vitamin K regeneration. The most common Vitamin K antagonist drug is warfarin, which interferes with blood clotting by inhibiting the Vitamin K reductase enzymes, thus blocking the production of Vitamin K and γ-Carboxylation, without them, Factor II, VII, IX, X, Protein C and S cannot form complexes and participate in the coagulation process. Warfarin is useful for people at risk of developing harmful clots in the blood, such as in certain clotting disorders.

3. Specific inhibitors of thrombin

These are based on hirudin and are direct inhibitors to thrombin. Hirudin was first discovered on blood sucking organisms, these organisms react to blood clotting process by releasing hirudin because they can’t suck the blood when it is coagulated. But hirudin by itself can be dangerous, because it binds to thrombin in an irreversible reaction and requires constant monitoring of the patient. To overcome this problem, a type of hirudin is used, which has a 20 amino acid sequence known as bivalirudin, its is much safer for long term use because its actions are reversible.

Common disease and disorders related to blood clotting

Many disease and disorders that are related to blood clotting exist, they can cause extensive and continuous bleeding for no reason or promote platelet aggregation when there is no damage to blood vessels. Some of them are Genetical, meaning that they can be inherited from the parents, while others are environmental. The common diseases are:

1. Hemophilia Type A and Type B

Both Type A and B is a disorder that is characterized by the absence of clotting Factors, Type A lacks Factor VIII while Type B lacks Factor IX, causing reduced or the lack of clot formation in bleeding situations. It is genetically inherited by genes that are recessive and are located on the X chromosome so its more common in males than females. Its symptoms can be mild, moderate and severe, including excessive and prolonged bleeding during a cut or surgery, , pain and swelling in joints as a result of bleeding, and in complicated cases it can cause numbness, repeated vomiting and double vision. Hemophilia Type A is more common and can be more severe than Type B.

2. Clotting Factor deficiencies

It is a rare disorder in which one or more clotting factors (II, V, VII, X, XII) is absent or not working properly, they can lead to abnormal blood clotting during bleeding.

3. Van Willebrand’s disease

One of the most common bleeding disorders, it is the result of the absence of the Van Willebrand’s Factor in the blood, which is very important for the coagulation process and platelet aggregation at the damaged site. Without vWF clotting will not occur at the damaged site which results in excessive bleeding.

Many more diseases exist that is related to blood clotting, such as Factor V Leiden, Bernard-Soulier syndrome, Thrombocytopenic purpura and kwashiorkor (malnutrition of protein resulting in low concentration of clotting factors).

Conclusion

From the topics and process I mentioned above, we can conclude and summarize the following points:

  • •emostasis is divided into 3 steps, these include vascular spasm, platelet aggregation and coagulation, during which the vessel is dilated to increase blood flow, platelets are activated and aggregated at the site of bleeding and several clotting factors participate in a cascade of reactions to form the fibrin mesh.
  • Fibrinolysis is breakdown of the fibrin mesh by the plasma protein plasmin, which is a regulator of the blood clotting process along with APC, Thrombin and serpins
  • Several drugs effect the blood clotting cascade, these include the heparins (activators of antithrombin III), Vitamin K antagonists such as warfarin (inhibits vitamin K reductase) and direct thrombin inhibitors based on hirudin.
  • Many clinical conditions result in deficiency of clotting factors or receptors or any of the substrates that participates in the blood clotting process, such as Hemophilia A and B, which are X- linked disorders that cause extensive bleeding in joints and during cuts. Another example is clotting factor deficiencies, although pretty rare, they can be critical conditions. And lastly, there is Van Willebrand’s disease, which is characterized by absence of vWF in the blood.

References

  1. Marks’ Basic Medical Biochemistry (A Clinical Approach) – Lieberman & Marks – 4th Edition – Section 8 – Chapter 45 – Blood plasma proteins, Coagulations and Fibrinolysis.
  2. Article about Biochemistry of clotting factors. https://www.ncbi.nlm.nih.gov/books/NBK507850/
  3. Anticlotting mechanisms, Physiology and Pathology. https://academic.oup.com/bjaed/article/13/3/87/278964
  4. Warfarin. https://www.uptodate.com/contents/warfarin-coumadin-beyond-the-basics
  5. Bleeding disorders. https://www.healthline.com/health/bleeding-disorders#types
  6. Vitamin K antagonist drugs. https://www.drugbank.ca/categories/DBCAT002267
  7. Heparins. https://www.drugs.com/drug-class/heparins.html
  8. Symptoms and causes of Hemophilia. https://www.mayoclinic.org/diseases-conditions/hemophilia/symptoms-causes/syc-20373327
  9. List of anticoagulant drugs. https://www.medicinenet.com/anticoagulants_drug_class_of_blood_thinners/article.htm#who_shouldnt_take_anticoagulants

The Necessity Of Instant Blood Notification System

INTRODUCTION

The last decade has witnessed an explosive growth in the field of technology. Everything is fast and instant in this modern world of smart technology. Today, there is no place for error and very much time-consuming works.

Currently, we are developing a website, the website is a collection of pages on the www (World Wide Web) that contains specific information which was all provided by one person or organization. Blood notifies website provides information about the need for blood. It provides direct notifies to all the person that is available in the chat room as well as it gives a direct message in the mobile phone. Some part of our website is dynamic and some part is static. This website is used to deliver regularly changes in need of blood. Users are able to contact the donor. So this website can prove to be a very effective way of searching blood for an emergency.

PROBLEM STATEMENT

Existing system

The existing system of instant notification system is that the hospital or health centers will send the instant message on the donor’s mobile phone when emergency blood needed or shortage of blood with patient details, hospital details emergency case detail, contact person details. The whole process might be time consuming as well as the donor’s get proper details of patient and related case and address. In this web-based instant blood notification system people have engage in different palace of the nation the system will provide location based option to find and send the instant notification to the donor with the needed location based area or palace. On other hand, many people in Nepal haven’t knowledge about donating the blood many people have confusion where to donate and if people donate the blood they have fear to blood center used to sale their blood with high rates so the system will provide the platform to direct contact with patient to donating the blood with proper details and feel fearless to donating the blood.

Limitation of the Existing System

  • Time consuming while retrieving the information of a student.
  • Takes more human efforts and physical records.
  • No proper format is used for storing the details of student information.
  • No accessibility is provided to students for their details.

Proposed System

The idea of instant blood notification system is common in sedwan. But these kinds of system don’t exist in Nepal which is the one of the drawbacks for the beautiful country like ours. Instant Blood Notification system will basically bridge the Donor’s and Patient who want to donate blood and feel fearless to donate blood. These kinds of system will provide donors to find their Destination palace to direct donate fresh blood with the requirements and feel fearless

OBJECTIVES

The proposed instant blood notification system will have the following features:

  • Develop an interactive web application with a user friendly search interface.
  • Registration Facility with Proper Documentation and Details.
  • The system will be capable to build the User trust with proper Details and User Verification of User Blood Request and Notification Services.

Agile Methodologies have overcome the traditional methods of waterfall model by becoming flexible, fast, lean, responsive, and consistent. This method focuses on people and is more communication-oriented and tested in a dynamic environment and proves to be very flexible by adapting to the change happening in the business. It’s include regular inspection in a disciplined manner, which consequently improves the leadership qualities to boost the teamwork and follows best practices that help in getting high-quality software very quickly.

TOOLS AND TECHNOLOGIES

PHP

PHP is known as a scripting language. It is a programming language which is used by developers to make dynamic contents which interacts with the database present on the web server. How PHP works is: it is embedded into a HTML document and when the user requests the document, the server runs the PHP code and embeds the output of the code into the document and sends the document to the person who requested it.

I am using PHP because I need my site to be dynamic, also I’m using databases and I’m going to be utilizing various functions provided by Object Oriented PHP

Bootstrap

Bootstrap is a free and open-source CSS framework. Bootstrap help us to design websites faster and easier. It includes HTML and CSS based design templates for forms, buttons, tables, navigation, image carousels, etc. Bootstrap’s responsive CSS adjusts to phones, tablets, and desktops. Bootstrap is compatible with all modern browsers (Chrome, Firefox, Internet Explorer, Safari, and Opera).

MySQL:

MySQL is a freely available open source Relational Database Management System (RDBMS) that uses Structured Query Language (SQL). SQL is the most popular language for adding, accessing and managing content in a database. It is most noted for its quick processing, proven reliability, ease and flexibility of use. MySQL is an essential part of almost every open source PHP application. It offers a lot of free MySQL tools including CMS systems, forums, galleries, blogs, shopping carts and more.

CSS

CSS is used to decorate HTML document. It is used by web developers to style html document, make it more visually appealing to the users. It can be embedded inside a HTML document or in a separate file. The browser while rendering HTML document also loads the CSS and gives formatting, color or style to the documents as per what’s written in the CSS document.

I’m going to be using CSS to interacted webpage to make it visually appealing to the users and correctly format the webpage.

JavaScript

JavaScript is the most popular scripting language which is used by developers to make interactive HTML pages. JavaScript is feature packed and can be used to do various computing on the user machine. It decreases the load that falls on the webserver as it uses the user computer to execute the script. It can be used to validate data, create interactive menu, and many more things. It is supported by every popular browser which makes it an easy choice for developers.

I’m going to be using JavaScript to make my site interactive and decrease the server load. Mainly I think I’ll use it for form validation, interactive menus and image or text sliders.

BACKGROUND STUDY

Government of Nepal, in its policy declaration of 1991, has mandated the Nepal Red Cross Society as the sole authority in conducting blood programs in Nepal. Therefore, a great responsibility has fallen on the Society and to prove its capability, it is systematically strengthening itself with resources available nationally and exploring resource possibilities internationally. The Kathmandu-based Central Blood transfusion service so far is the only referral center for the whole country, has been planning not only to upgrade the Centre but also in upgrading regional blood centers of Biratnagar, Pokhara, Nepalgunj, and Chitwan. It is also considering the possibilities of upgrading the Dharan and Dhangadhi blood centers in view of the establishments there of major hospitals and coverage area. As it stands today, there are 21 district level blood banks, emergency units in 17 and 25 hospital units of the services in the country.

Instant Blood Notification system will basically bridge the Donor’s and Patient who want to donate blood and feel fearless to donate blood. These kinds of system will provide donors to find their Destination palace to direct donate fresh blood with the requirements and feel fearless.

In the context of Nepal, there is no any system which have such type of feature to send instant message to the donor with patient details and blood requirement and case. Rather there is the traditional type blood donating and blood searching process to visiting the blood banks and buy with high rates. In such system or process there would be more time consuming likewise, there is the probability that donor’s has proper details where to donate blood and which patient with their related case. These are the disadvantages we might face in such type of traditional process of searching for blood visiting blood banks. Through my research I also found similar type of application, where people donate the blood when they get an instant message with patient, hospital and required blood with the type of blood group.

Blood connects us all is the type of application where The text message initiative, launched last year by the Stockholm blood donation service Blodcentralen, uses technology to recruit and retain new donors. Donors receive an automated text telling them when their blood has made it into a fellow human being’s veins. It was an ordinary event, but this was no ordinary text. It was a thank you, notifying him that the blood he recently donated had been given to a patient.

Conclusion

As per the research on this system the Instant blood notification system is considered as a blood manages system when emergency blood are required. It is difficult to manage the blood when emergency blood required and many people will have died due to blood shortage. There are user register services and as well as donor. This system provides direct connection between donor and patient as well as hospitals with verified details.

Android App For Blood Bank

ABSTRACT

The seminar titled “ANDROID APP FOR BLOOD BANK” acts as an important role in saving life of human beings , which is its main aim. This project is developed, so that users of the app can view the information about registered blood donors such as name, address, and other such personal information along with their details of blood group and other medical information of donor. Thus this application helps to select the right donor instantly using medical details along with the blood group. This project acts as a link between the person interested in donating their blood and those who are in need of the blood. The one who require blood can search for the donor by the details given in the app. The main aim of developing our application is to reduce the time to a greater extent that is spent in searching for the right donor and the availability of blood required.

INTRODUCTION

There are many useful android based applications, that serves variety of purposes to humans. Our project titled “ANDROID APP FOR BLOOD BANK”, provides a suitable way to approach an issue ,which is most important today. The project is developed to make the process of blood donation in a convenient and more sophisticated manner. It is developed with the motive of saving life of many human beings. It helps the users to check the availability of the required blood and the right donor along with their contact details. The users can view the availability of blood and may also register to donate blood if he/she wishes to. This application does not require internet access for its working. It gets the details of the donors as input and displays them so that others can use that to check for the availability of blood late

LITERATURE REVIEW

ANDROID BLOOD BANK

In “Android blood bank” by prof. Snigdha et.al proposed an application for blood donor. In that application the donor can find the exact path by using GPS(Global Positioning System). The detail of blood donors will be saved. private data and confidential datas are only viewed by the administrator. They have methodologies like PHP, MY SQL, Android.

A LIFE SAVING APPLICATION

In “MBB:A Life Saving Application ” by Narendra Gupta et.al has proposed a method to create a website with android application. In there application they has proposed, the donor are tracked by Geographic Information System(GIS). The purpose of their website is used to update their current system where datas can only viewed by authorized user. They contain two device type: 1)An android phone with android os, 2) A computer for website and database which is used to store the information about the donor.

AN ANDROID APPLICATION FOR VOLUNTEER BLOOD DONORS

In “ An Android Application for volunteer Blood Donors ” by sultan Turhan proposed an application for volunteer blood donor, main aim of this application is to notify regularly the donor location to Rh**. Rh** is a smart information system which aim to control the blood donation and blood supply chain.

ANDROID BASED HEALTH APPLICATION IN CLOUD COMPUTING

In “Android Based Health Application in Cloud Computing For Blood Bank” by Sayali Dhond has proposed android based application for blood donor, in which the donors information are stored in cloud. They user shoud request blood on the cloud and the information are sent to nearby hospital or blood donor who are register on cloud.

THE OPTIMIZATION OF BLOOD DONOR INFORMATION AND MANAGEMENT SYSTEM bt TECHNOPEDIA

In “The Optimization of Blood Donor Information andManagement System bt Technopedia” by P. Priya et.al has proposed a method of creating website with android application in which the blood donor can easily available within the required time. The donor who are nearby location are easily tracked by GIS. In this application the website is to update the information of donor who have already given blood in various hospital. While comparing to manual system, computer based information system are time consuming, laborious . Data mining concept is important benefits to the blood bank sector, data mining tool can be a fundamental tool to analyze the data gathered by blood banks through their information system.

ANDROID BLOOD DONOR LIFE SAVING APPLICATION INCLOUD COMPUTING

In “Android Blood Donor Life Saving Application in CloudC omputing” by T. Hilda Jenipha and R. Backiyalakshmi has proposed an application for blood donation. In this application during emergency it will list of donors in the city. They can enable immediate access to donors information and location.

FUNCTIONALITIES:

  • Blood donation application update information about the blooddonation camp.
  • The system provide authorized features so that the private and confidential data are only view by the authorized user.
  • The system will keep record of every donor, in order to keep track of blood stock.
  • The donor who are all nearby location are tracked by the GIS.

EXISTING ISSUES

In existing there is no proper care about the people who donate blood to patients. In case if the donor has or had any medical problem and comes toward to donate blood to the patient then it may lead to threat. Hence medical history of donor should be updated .

Medical issues would be like:

  • A person who have anemia should not donate blood.
  • Donar who having diseases that are transmissible through bloodare not request to donate blood.
  • People who are unweighted for height from their height should not donate blood.
  • Pregnant women or recent child birth women should not donate blood.

PROBLEM DEFINITION

In present scenario, people search for blood donors manually or through blood bank websites, blood bank centers or by toll free numbers. But these process are time consuming and it also involves lots of manual work. The problem faced now includes,

  • Going to blood bank centers each time consumes more time and effort.
  • The user may have to wait for the availability of blood each time.

PROPOSED SYSTEM

Mobile blood bank is a mobile based project . Mobile is a portable device, so it can move easily from one place to another place easily. Hence it is the best choice for communication . By using this application people who wants to donate their blood can register in this application by providing their details. Person who require blood can search and find the appropriate donors using this application. On searching, the list of donors will be displayed by which the users can communicate with them easily and get the required blood.

ANALYSIS AND DESIGN

Blood banks are centres which involved in collecting, processing and storing blood for research and medical purposes. The main motive of collecting blood is to supply patients who need blood for surgery or for treatment of any disease. The given project is one of the great life saver . This application is developed with the motive of reducing the time spent on searching the blood donors during emergency situations. Our application helps in keeping track of all the latest updates relevant to the people who have donated blood in case of emergency. It will include all the details related to the donor such as their name, their address, their mobile number, their blood group and so on. The one who are in the need of any blood group can access the available group of bloods in nearby blood banks as specified in the application as well as details of those who can donate blood in urgent.

CONCLUSION

By using our application, we can overcome the problem which we are facing in current scenario by introducing a new way to find blood donors. We have proposed an efficient and reliable android blood bank application, which is most required and a valuable product to health sector, where the lives are been saved. Any number of donors can get themselves registered through these improved system. In future, the application will be modified and made accessible online, which will prove to be very useful to the society.

REFERENCES

  1. Programming Android: Java Programming for the New Generation of Mobile Devices (2nd Edition) book by Zigurd Mednieks, Laird Dornin, G. Blake Meike, Masumi Nakamura.
  2. Android Application Development For Dummies (Second Edition) book by Donn.
  3. Beginning Android Programming with Android Studio book by J F DiMazrio.
  4. Android Studio development Essentials book by Neil Smith .
  5. Udacity – Android Application development Nanodegree.

What Does Blood Symbolize in Macbeth

Who would thought something as simple as blood could change a story drastically . Throughout the story blood symbolized, corruption, greed, and ultimately guilt. The two central characters, Macbeth and Lady Macbeth, in the play Macbeth is heavily affected by Lady Macbeth’s wickedness. Lady Macbeth designs a successful manipulative plan to have her husband kill king Duncan of Scotland, she does so by testing his manhood and calling him a coward. But, when you think of murder, the first thing that comes to mind is blood. Blood isn’t just a flowing substance going through your veins, the meaning/ feeling of blood can come with a lot of potential circumstances that led the story to end, how it ended. William Shakespeare, Macbeth, shows how the taste of blood, feeling of guilt/ remorse can affect not only the characters in the play, but as well as the story as a whole. Blood symbolism is often used as an abundance of allusion, in Shakespeare’s plays. This is especially true in Macbeth as the many quotations pertaining to blood show as such.

As the story progresses, it is evident that the symbol of blood is used as a symbol of assassination and guiltiness. As Macbeth states In act 2 scene 1, “And thy blade and dudgeon hours of blood, which was not so before. There’s no such things: it is the bloody business which informs this to mine eyes.” This quote reveals the hesitation in Macbeth’s body before he attempts to kill Duncan. He visualizes a floating dagger floating to him, which ultimately steers him to proceed into Duncan’s room. Macbeth’s is at an extremely heightened emotional state at this point. He immediately starts to rethink his desire to become king, as he finishes the execution, the dagger projects the symbol of remorse and guilt. As Macbeth thinks about the murder, the thought is symbolized by the bloody dagger, and is making his emotions extremely worrisome. Macbeth states in act 2, scene 2, lines 55-61, “What hands are here! Ha, they pluck out mine eyes. Will all great Neptune’s ocean wash this blood Clean from my hand? No, this my hand will rather The multitudinous seas incarnadine, Making the green one red.”

The sight of blood is figuratively tearing his eyes out his head. His allusions pertaining to the blood being on his hands, shows as a sign of guilt and it tells the reader that he is in a constant state of thinking about it. He starts to believe that he’d never be able to wash the blood away and that he’d never be able to forgive himself of the filthy things he’s committed. The haunting guilt that is brought upon Macbeth changes his behavior as the story continues.

The regret that is running through Macbeth’s spirit is tainting with his behavior, which is caused by the symbolism of blood, it shows how Macbeth’s whole behavior changes. In act 3 scene 4 it states, “Thou canst not say I did it. Never shake / Thy gory locks at me” This quote reveals Macbeth’s regret/ remorse about killing Banquo. As Macbeth denies the act of killing Banquo, but he feels guilty for sending people to do so. Gory locks is a metaphor being used to visualize Banquo’s bloody body. He thinks about his old self which starts to put him in even more guilt. Banquo and Macbeth were known as really good friends, to have one of your best friends killed it’s obliged to bring guilt upon you. Hallucinations of the presence of Banquo’s bloody ghost is an important key point to Macbeth’s feelings of regret. An additional quote in act 3 scene 4, states, “I am in blood, sep’t in so far that, should I wade no more, returning were as tedious as go o’er.” This quote reveals his emotional state, he does not know what to do, but he does realize that he has to attempt to find peace for the crimes he committed but with all the guilt on his conscious notices that it’ll be very hard to do so. The change in Macbeth’s character is a dramatic function ultimately changing the story and what could’ve been.

Furthermore, the symbolism of blood reveals the shift in Lady Macbeth’s mental state. A quote in act 2 scene 2, states, “My hands are of your colour dc, but I am ashamed to wear a heart so white.” As Lady Macbeth first designs a plan to have Macbeth, kill Duncan, she displays that she lacks care and has a very nonchalant attitude towards the situation. She tries to test Macbeth’s manhood by telling Macbeth he is too pure and weak; has a white heart- she feels like she did nothing wrong, but is ultimately just as guilty as Macbeth. A sign of guilt shows as she “easily” washes her hands. She tried to show no sign of care, unlike her husband; she tries to prove she is a strong individual and would do anything to make it to the top. Also a quote in act 5, scene 1, Lady Macbeth states “Out, damned spot! Out i say!” As Macbeth washes his hands, she starts to feel the wrath of guilt. Which she desperately tried to not feel. She continuously tries to rinse this spot of blood she envisions off her hands- the blood seemed like it refused to come off, causing her to start hallucinating. She couldn’t take the guilt, trying to free her consciousness, she sadly kills herself. Her actions conclude that it’s evident that the symbolism of blood was very important to analyze, in order to have a deeper meaning of the story and how it played out. It led up to Lady Macbeth killing herself, with all the guilt and regret it brought upon her.

To conclude, the symbol of blood is used as a symbol of corruption, guilt, and remorse . In most of Shakespeare plays blood symbolizes murder and other acts like it, but in the end it ultimately brings guilt upon the characters. Lady Macbeth and Macbeth are two prime examples of what blood can cause upon the characters and how it can eventually change the story. They’re minds were continuously tormented by the evil acts they committed which were ultimately made upon greed. The plodding of Macbeth is what he suffered from and Lady Macbeth was driven out of her mind, causing her to hallucinate, which led to her suicide. Blood symbolism changed how each of the characters acted from the beginning to the end of the story. The usage of blood is used by William to enhance the reader’s comprehension of the character shifts through the story.

Impact Of Mobile Applications On Blood Donation Process

Abstract

There is extensive research in the field of blood donation. Blood donation is an honorable and humane act. Technology has been spreading its root everywhere in almost every field around the world. The medical field is also full of the application and implementation of the technology and new advances in the smart innovative fields. The use of technology for the wellbeing of human life is the best possible utilization of the resources. This review paper encompasses the utilization of mobile application increases the number of those who do blood donations in Saudi Arabia. It generally reviews the research studies conducted by other scholars in regards to the development of mobile applications to search, collect, inform, store and distribute every type of blood in Saudi Arabia. Different organizations such as Saudi Ministry of Health and Saudi Red Crescent Authority are aiding in the process of effective blood donation utilizing the technology. However, there is need of innovative thoughts with development of effective, secure database for achieving better outcomes out of this combination.

Introduction

At the turn of the twentieth century, fundamental changes began to occur in human services. Specialists found human blood bunches in the mid-1900s, and it is a standout amongst the most critical restorative data from that point onward. In 1907, the principal cross coordinating occurred, which implies the examination of the inconsistency of the giver’s and the beneficiary’s blood type. Ten years after it, the primary blood warehouse was made. In the following two decades, the blood transfusion benefits just as blood offices were made and the act of blood donation systematized [1]

Taking fresh blood and its preservation of every blood donor society or organization. Blood focus needs quality frameworks and innovative foundation to keep up great lab rehearses regardless of substantial remaining task. In this way enrollment of intentional contributors, appropriate gathering and part partition procedure and screening of gathered blood for transfusion transmissible diseases (TTI) are the fundamental necessities of the blood security. Immunohematology lab capacities 24 hours, 365 days and in charge of providing perfect blood. To counteract manual blunders this research facility ought to ideally have computerization.

As per World Health Organization (WHO), India is confronting 30%-35% of a blood shortage consistently. Despite the fact that India has over 1.2 billion populace, it is yet confronting blood shortage. The issue is not absence of donors, however discovering giver when required. Profiting medicinal services office by means of portable is another point of view, [5], which plans to expand social insurance administration. Expanded utilization of cell phone affects the fast development of human services. Numerous portable application improvement organization India, USA, and UK have created versatile applications for finding blood banks.

The mobile applications are area based as well as organization based. They help in keeping track of the earlier blood donors and receivers. They allow the history to help the organizers track the donor as well as receiver’s needs [4].

Methods

Research papers relating to the utilization of mobile applications in blood donations were identified from Google Scholar, Science Direct, NCBI, PubMed (up to 2019), and World Wide Web (blogs, news, and magazine articles). The following key terms were searched as headings or text words in the titles and abstracts: “Blood Donation, Mobile Applications, Technology, and Social Media, Saudi Arabia”. The relevant data and papers were evaluated properly and the following results were obtained.

Results

These days, blood donation is a broad work on sparing a huge number of lives. As indicated by the estimations of the WHO, around 108 million units of gave blood are gathered overall yearly; and around 100 blood focuses in 168 nations report gathering a sum of 83 million blood donations. In spite of the fact that an expansion of 10.7 million blood donations from willful unpaid benefactors has been accounted from 2008 to 2013, we cannot take a load off about this number, since somebody needs blood like clockwork. What’s more, as a rule, it is exceptionally hard to discover blood givers.

The same number of people know the procedure resembles the accompanying: the benefactor goes into a blood donation focus or a human services office. Specialists screen benefactors for wellbeing dangers, analyze them for indications of ailments transmissible through blood donation, and decide their blood type. At that point, blood is gotten ordinarily as entire blood from a vein, and the typical measure of donation is 450 milliliters. The gathered blood is generally put away in a blood bank as independent segments, and can be put away for a brief timeframe. Red blood cells (RBC), the most regularly utilized segment, have a timeframe of realistic usability of 35– 42 days at refrigerated temperatures [5].

In one of the articles, the researchers explained that blood donation has three sorts: it very well may be intentional, paid or performed with the assistance of relatives. The last may happen when a patient is in a dangerous condition because of a fender bender or whatever other mishap, where it is important to act in all respects rapidly.