Amanda Maxwell

Amanda Maxwell is the lead science writer at Vancouver-based Talk Science to Me. 

Meet Canada's Blood-Typing Pioneers


Thursday, July 06, 2017

Innovation150 series: As Canada celebrates 150 years we look back on Canadian innovations in transfusion medicine over the years. A series of posts over the next few weeks feature remarkable Canadian progress - past, present and future. #Innovation150. 

 

Blood-typing pioneers

Canada’s blood transfusion service and the patients who benefit from it owe a great deal to pioneering innovation in the field of blood typing. Work by immunohematologists Marie Crookston at the University of Toronto and Dr. Bruce Chown, Dr. Jack Bowman and team at the Winnipeg Rh Laboratory in the mid-twentieth century advanced clinical knowledge of transfusion reactions due to blood cell antibody responses. Their studies made the transfusion service aware of these potentially life-threatening reactions and gave clinicians new treatments. Furthermore, results like these from the broader field of blood typing also paved the way for current research looking at camouflaging blood cells and making artificial universal donor blood.

 

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The University of Manitoba hosts an excellent look back at the history of the Winnipeg Rh Laboratory. URL: http://medheritage.lib.umanitoba.ca/?page_id=73 

Dr. Bruce Chown and the Winnipeg Rh Laboratory

Dr. Bruce Chown graduated from the University of Manitoba medical school in 1922. He spent three years in pediatric research in the United States before returning to the Children’s Hospital in Winnipeg. In 1940, his research interests turned to human blood groups in general, and newborn and infant conditions in particular.

Rhesus Factor

At the time, Rhesus (Rh) factor on the surface of red blood cells and the Rh factor system were not fully understood. Although Rh factor was discovered by Karl Landsteiner in 1937, its importance became apparent only through follow-up work in 1940. A paper on hemolytic disease of newborn babies showed that this newly discovered blood type caused neonatal deaths and severe transfusion reactions.

Rh factor is a blood group antigen, a protein that spans across the red cell membrane to the outside of the cell. Humans either do or do not possess these markers, hence the blood-typing classifications Rh+ or Rh−. There are several different Rh antigens, but the most common one referred to is termed D. Normally the Rh system does not cause a problem unless an Rh− individual is sensitized and carries anti-Rh antibodies. This is rare, but sensitization can happen during pregnancy and with blood transfusion. Sensitized individuals will therefore destroy any Rh+ red blood cells they encounter.

Maternal Sensitization and Hemolytic Disease of the Newborn

Sensitization of Rh− mothers can occur during pregnancy, since fetal blood can cross the placenta and mix with the mother’s circulation, and at childbirth.

So, if an Rh− woman carries an Rh+ baby, she will create antibodies to Rh factor through alloimmunization in her first pregnancy. Although nothing happens during the first pregnancy, any further pregnancies that she has with an Rh+ partner will be affected. Quite simply, the mother’s antibodies against Rh factor cross the placental circulation to attack and destroy her developing baby’s red blood cells.

Before researchers understood this process, hundreds of families either lost or gave birth to seriously disabled babies in second and subsequent pregnancies due to erythroblastosis fetalis, or hemolytic disease of the newborn (HDN). A lot of families never had more than one child.

And this is what Chown and the Winnipeg Rh Laboratory set out to put right in 1940.

Read more: Dr. Bruce Chown and the Winnipeg Rh Laboratory: From Tragedy to Triumph

Preventing Loss and Saving Newborns

Chown and Bowman, and later Dr. Alvin Zipursky, established various protocols to save alloimmunized Rh+ newborns from hemolytic crises, disability and death.

First, with treatment, Chown initiated prompt transfusion with “clean” blood to save a newborn’s life. Chown realized that the red blood cell destruction was somehow associated with a factor in the baby’s circulation, and the exchange transfusion removed the dangerous maternal anti-Rh antibodies for protection. Along with Bowman, he pioneered even earlier transfusion, setting up the exchange treatment for the developing fetus in utero before birth.

The lab also developed early-stage testing for Rh status by examining amniotic fluid around the fetus and a proactive treatment for pregnant Rh− women using anti-Rh immunoglobulin, or anti-D. This antenatal prophylaxis, where the woman receives anti-D intramuscularly during her pregnancy, destroys fetal Rh+ cells before her immune system becomes sensitized into making her own anti-Rh antibodies and thus protects the developing fetus. Thanks to this pioneering work, Rh immune globulin (WinRho) treatment is widely available to all mothers in Canada and across the world.

Read more ‘My goal? Very modest. Wipe out Rh disease’  (Toronto Star)

Marie Crookston, Immunohematologist

At around the same time, another Canadian immunohematologist was deciphering the antigenic markers on the surface of blood cells. Marie Crookston (née Cutbush) got her Bachelor of Science degree in Melbourne, Australia, in 1946 before moving to London, United Kingdom, to work in hematology and transfusion medicine at the Medical Research Council (MRC) with Dr. P.L. Mollison.    

Before marrying and moving to Canada, Crookston worked on categorizing new blood groups. In Canada, she raised a family while working in transfusion medicine at the University of Toronto, researching newborn exchange transfusion, transfusion reactions, long-term frozen blood storage and transfusion medicine.

Read more: Blood Transfusionist Extraordinaire: Marie Cutbush Crookston (Transfusion Medicine Reviews)

 

Blood types and transfusion reactions

Blood groups ABO and Rh comprise markers sitting on the red blood cell membrane; the ABO markers are sugars, and the Rh factors are proteins. These act as antigens, sensitizing individuals who do not possess the markers into making antibodies against them. Once sensitized through exposure, the antibodies then destroy cells containing the markers by identifying them as foreign. This is benign for the host unless they are given blood of an incompatible group through transfusion or as maternal antibodies such as in HDN.

Duffy Group and hemolytic disease

Crookston and Mollison characterized a less common blood group known as the Duffy group. These glycoproteins are cell-surface receptors involved in inflammatory responses, and are found on red blood cells as well as other tissues throughout the body. Once sensitized, individuals can experience transfusion reactions from incompatible blood. Crookston characterized anti-Fya, one of the antibodies implicated in Duffy group transfusion reactions; it is also involved in a hemolytic condition in newborn babies similar to but less common than HDN.

Crookston also characterized another circulating antibody involved in transfusion reactions, anti-Lub. Although uncommon, this immune reaction also causes instances of HDN. As an assistant professor in the Department of Pathology at the University of Toronto, Crookston continued her research into immunohematology, looking at antibodies and agglutinins, which led to the development of a Rh vaccine for use during pregnancy and delivery.

Chapter 12, Hemolytic Disease of the Fetus and Newborn and Perinatal Immune Thrombocytopenia, Clinical Guide to Transfusion by Drs. Gwen Clarke and Judy Hannon (Canadian Blood Services)

Blood type basics for a universal donor?

There are many different types of blood group in existence, but the main ones that commonly cause transfusion reactions are the ABO and Rh systems. It is important for transfusion clinicians to carry out blood typing before treating patients to avoid serious reactions. However, maintaining sufficient stocks of compatible blood types is a challenge, especially for rare groups and during disasters.

Blood type O Rh− is also described as the universal donor blood, since the red blood cells do not carry A, B or RhD surface antigens. O Rh− can therefore be given to almost any patient, and blood banks try to keep high levels of it in stock. However, research into creating artificial universal donor blood is under way.

Dr. Mark Scott at the Centre for Blood Research

Dr. Mark Scott, a senior investigator with the Canadian Blood Services and the Centre for Blood Research at the University of British Columbia (UBC) is pinning camouflage to red blood cells to help them avoid a patient’s immune system. The camouflage molecule, known as PEG, sits on the cell surface and blocks antibody attack, thus protecting the donor cells from destruction. Another approach is to snip the red cell antigens from the cell membrane. UBC associate professor Dr. Jayachandran Kizhakkedathu and team have developed an enzyme that does just that, making artificial O− blood for transfusion.

 

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Research like this may make it possible for blood banks and transfusion services to respond quickly to patient needs in the future, serving disaster medicine where large volumes are required almost instantly, and providing safe products for patients with rare blood groups. Without pioneering basic research into blood type characterization from immunohematologists like Crookston and Chown, the idea of an artificial universal donor blood would be impossible.

Read more:

This post was prepared by Amanda Maxwell, for Canadian Blood Services, with grateful thanks to Dr. Jacalyn Duffin, Queen’s University, Kingston, Ontario, for additional insights and materials.


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration. Find out more about our research impact

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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Wartime Service and Canadian Transfusion Medicine


Thursday, June 29, 2017

Innovation150 series: As Canada celebrates 150 years we look back on Canadian innovations in transfusion medicine over the years. A series of posts over the next few weeks feature remarkable Canadian progress -- past, present and future. #Innovation150.

 

Modern blood banking and transfusion medicine owe a great deal to Canadian wartime pioneers in battlefield medicine. For example, Dr. Lawrence Bruce Robertson’s insistence on whole blood for treatment of battlefield shock and hemorrhage established its medical importance in transfusion. This happened just as research on sodium citrate as an anticoagulant and buffers for red blood cell storage made advance collection from donors a more feasible option. However, it took another war before a civilian blood banking and transfusion service got started in Canada. Again, Canadian residents can thank pioneering wartime doctors for making it possible.

Dr. Norman Bethune and the Canadian Blood Transfusion Unit

Mobile blood banking for transfusion medicine featured in front-line medicine during the Spanish Civil War (1936–1939), when Canadian doctor Norman Bethune volunteered for action alongside the International Brigade. After receiving his medical degree in 1916, Bethune completed internships and worked in private practice before studying under Dr. Edward Archibald in thoracic surgery in Montreal.

This was the same Archibald who pioneered sodium citrate as an anticoagulant during World War I battlefield transfusion treatment. When Bethune didn’t find an opportunity to offer his surgical services in Spain, it was this experience in transfusion medicine from surgical practice that proved most valuable. Knowing that soldiers with battlefield injuries frequently benefit from treatment with whole blood, he saw an opportunity to support patients on the front line, using his transfusion experience to outfit a van as a mobile blood service.

 

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Dr. Norman Bethune (right) Canadian Blood Transfusion Unit which operated during the Spanish Civil War circa 1936-1938, Spain. Source: Library and Archives Canada Copyright: Expired.

Mobile Blood Banking

Bethune’s Canadian Blood Transfusion Unit operated out of Madrid and covered a wider area than the other mobile services operating at the time. It tested out the refrigerated storage developed by a Spanish mobile transfusion team under Dr. Frederic Durán-Jordà, a hematologist working out of Barcelona.

The Canadian Blood Transfusion Unit brought blood donated by civilians to front-line hospitals and organized rapid transport of type O blood, the universal donor. Bethune claimed in one interview that the unit had collected and processed more than 340 litres of blood over one year of service.

Although Bethune left Spain after a year, his work with the mobile transfusion service is seen as an important contribution to modern Canadian transfusion service.

  • Bethune organized a civilian volunteer base for donations and rapid transport for type O blood to the front line.

Dr. Charles Best and blood products for military hospitals

Dr. Charles Best, possibly most famous for his association with Frederick Banting’s Nobel Prize–winning work on insulin, pioneered methods for blood product storage that made them easier to ship overseas to the battle areas in World War II. His research and development of dried plasma products and validation of serum instead of whole blood for treating shock increased the versatility of blood banking and transfusion services for emergency medicine. This work, in conjunction with the Canadian Red Cross and government support, led to the establishment of the country’s first national blood banking and transfusion service.

  • Best is most famous for his association with the Nobel Prize in Medicine for the isolation of insulin. Best was the student helper Banting acquired to help with his lab work one summer.

Blood products for easy transport and for transfusion safety

When Banting won the Nobel Prize in Medicine in 1923, he shared the prize money with his student , Charles Best. With this money and his newly acquired medical fame, Best joined colleagues at Connaught Laboratories, redirecting his pre-War research program to explore the limitations encountered with transfusion medicine during World War I and investigate novel ways to store blood products.

Problems with whole-blood coagulation and storage meant that blood stocks were not plentiful, and soldiers often acted as “walking blood donors.” Furthermore, transfusion reactions due to incorrect blood-group matches still limited the service. Although further work had taken place to clarify blood typing in the years since World War I, incompatible transfusions still caused deaths. The crude matching tests that mixed donor and patient blood to check for clumping before each transfusion weren’t always easy to read.

Concentrating on these challenges, Best and his team worked on methods for preserving blood in long-term storage, and for cell-free alternatives to whole blood that might reduce transfusion reactions.

Best and his colleagues developed methods of separating whole blood, removing the fluid components — plasma (the liquid left after cells are removed) and serum (plasma without clotting substance, fibrin) — from cells. Once dried, the blood products could be shipped in a more stable form with a greater shelf life. Once the product arrived at the battlefront, clinicians simply reconstituted it by adding sterile distilled water before transfusing it into patients.

 

 

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Human serum bottles and travel case, http://www.redcross.ca/history/artifacts/human-serum-bottles

The Serum Project

In addition to improving storage methods for blood products, Best also initiated the Serum Project. He demonstrated that administering serum rapidly improves the low blood pressure commonly encountered during shock. His experiments showed that following infusion, serum proteins remained in circulation long after colloids such as sodium chloride escaped. These proteins generated an osmotic pressure that helped build circulating volume to increase blood pressure. With this success, Best then optimized serum production and concentration methods, along with new drying techniques, so that the product could be shipped safely.

Canada’s civilian blood banking service

Best was also concerned with how this new medical advancement would be supported within Canada. He promoted voluntary donation, giving economic justification for this as a way to expand transfusion services to all Canadians, rich and poor. With this in mind, Best favoured the Canadian Red Cross for setting up national donation and blood banking, with initial efforts going to support the Armed Forces overseas. This set-up was successful, with massive public support for the war effort: “approximately 890,000 blood donations were collected from Canadians for military hospitals during the last year of the war” from a Canadian population at the time of only just over 11 million.

As a direct consequence of Best’s work in championing voluntary donation and alternative blood products, a civilian blood transfusion scheme and donor program began shortly after the war ended in 1945.

 

Written by Amanda Maxwell, with grateful thanks to Dr. Jacalyn Duffin, Queen’s University, Kingston, Ontario, for additional insights and materials.

 

References
Kapp, R.W. (1995). Charles H. Best, the Canadian Red Cross Society, and Canada’s First National Blood Donation ProgramCanadian Bulletin of Medical History, 12(1). http://dx.doi.org/10.3138/cbmh.12.1.27


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration. Find out more about our research impact

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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Dr. Lawrence Bruce Robertson and blood transfusion in the trenches of World War I


Wednesday, June 14, 2017

Innovation150 series: As Canada celebrates 150 years we look back on Canadian innovations in transfusion medicine. A series of posts over the weeks leading up to and following Canada's 150th birthday feature remarkable Canadian progress in transfusion medicine  past, present and future. #Innovation150. Read more Canadian Innovation stories at innovation150.ca

Modern Canadian blood banking and transfusion services can trace their origins to the trenches of World War I, thanks to the efforts of transfusion pioneer Dr. Lawrence Bruce Robertson. Robertson enlisted in the Canadian Army Medical Corps to support the British soldiers fighting in Europe. Along with his medical expertise, he brought modern transfusion knowledge from his postgraduate training in U.S. hospitals to the front line.

 

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L. Bruce Robertson beside Canadian Red Cross truck, ca. [1914-1918]. L. Bruce Robertson fonds, F 1374, Archives of Ontario, I0050290   Copyright: Queen’s Printer for Ontario

 

Robertson was born in Toronto. He graduated with a medical degree from the University of Toronto in 1909, interned at Toronto’s Hospital for Sick Children and then headed to Bellevue Hospital in New York City for further training. There, he learned a lot about new developments in transfusion medicine from American doctors who were leaders in the field. At the time, U.S. medical practice supported the theory that blood transfusion was a valid clinical treatment, even though the practice was hampered somewhat by an incomplete understanding of blood groups and the effect of incompatible transfusions. In New York, Robertson saw clinicians developing tools for transfusing whole blood from donor to patient more easily.

Blood collection and delivery, from donor to patient

Previously, transfusion practice required that blood be directly transfused from donor to patient to ensure continued flow: problems with blood clotting meant that the donor artery had to be surgically attached to the recipient vein. This cumbersome approach continued until clinicians introduced a cannula to link the vessels between donor and patient. From these surgical approaches, transfusion clinicians then developed methods that could measure transfused volumes, as well as avoid the need to perform complicated surgery. They used multiple syringes to quickly withdraw blood from the donor to transfuse into the patient. Other modifications included introducing a four-way stopcock into the flow line and flushing with saline to prevent clotting. In this way, multiple operators could very quickly withdraw larger amounts of whole blood to treat patients in need.

Whole blood as treatment

World War I started in July 1914. The hostilities quickly settled into trench warfare, with horrendous conditions and loss of life endured by both sides on the Western Front. Battle casualties frequently arrived at the field hospitals after many hours of lying in tremendous pain on the field. Their overwhelming injuries from shell explosions, shock and blood loss usually meant that these soldiers did not survive. Although surgical efforts became more courageous for treating abdominal wounds, for example, the British standard treatment of infusing normal saline did very little to stabilize shock and save these young soldiers.

By this time, clinicians in the U.S. understood the value of whole blood in medical treatment and the necessity of pre-transfusion testing for blood group compatibility. They also had a number of transfusion tools available, having moved away from direct artery-to-vein delivery. However, medics in Great Britain and Europe still favoured saline as their first choice for treating blood loss and weren’t as up-to-speed in transfusion delivery as their North American colleagues.

Normal saline — a balanced solution of sodium chloride similar in salt concentration to tissue fluid in the body — will expand blood volume when infused. However, since it lacks blood proteins it rapidly escapes from the circulation and does not maintain blood pressure in the long term.

At the Front Line: Canadian transfusion medicine

When Robertson and other Canadian doctors arrived at field stations on the front line, they quickly promoted whole blood as the treatment of choice for battlefield medicine. Robertson himself wrote three papers on its use under battle conditions, showing its success in four, 36 and 68 cases, respectively. The cases described primarily soldiers with battlefield injuries resulting in severe blood loss, with whole blood donations being taken from other patients considered healthy but unfit for fighting due to sprains and minor fractures. Robertson’s success in using whole blood for treating injured soldiers and the syringe and cannula method for transfusion spread among Canadian and then British medics.

Government of Ontario archives show that Robertson’s work was greatly appreciated among soldiers, with some contacting him giving thanks for saving their lives, and others asking for news on the outcome from their whole blood donation

Citrate anticoagulant for blood banking

Meanwhile, another development in transfusion medicine was gaining acceptance by battlefield medics. A major problem during transfusion was the rapid coagulation of blood. Once withdrawn from the donor into a collection syringe, whole blood activates a clotting cascade that results in the cells and platelets clumping together. This blocks needles and cannulas, making further collection or transfusion impossible. Doctors found that sodium citrate was an effective anticoagulant, which extended the time between donation and administration. U.S. doctor Oswald H. Robertson is usually given the credit for bringing this into front-line medical treatment, but according to the Canadian Dr. Lawrence Bruce Robertson, it is another Canadian, Major Edward Archibald, who deserves the credit, pioneering use of the anticoagulant from 1915 onward, prior to 1917 when the US entered the war.

However, the American O.H. Robertson’s work on citrated blood did introduce another useful tool for transfusion medicine: blood banking. One of the major problems facing doctors at front-line hospitals was availability of whole blood for transfusion; other patients became a walking blood bank of donors since coagulation made it impossible to build up stocks of whole blood in reserve. O.H. Robertson showed that blood could be collected in advance, treated with sodium citrate and then stored in sterile bottles on ice until needed.

Following the end of the war, Lawrence Bruce Robertson returned to Canada. He continued practising medicine, advancing his transfusion techniques while working at the Hospital for Sick Children in Toronto. He readily shared his pioneering work, bringing whole blood transfusion and exchange transfusion to treat a number of conditions, including burns and intoxication, to the attention of his colleagues. Unfortunately, Lawrence Bruce Robertson died in 1923. He is  recognized as being the founder of Canadian blood banking and transfusion medicine.

 

Written by Amanda Maxwell, with grateful thanks to Dr. Jacalyn Duffin, Queen’s University, Kingston, Ontario, for additional insights and materials.

 

Further reading

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration. Find out more about our research impact

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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Research matters at Canadian Blood Services


Wednesday, February 15, 2017

A searchable database showcasing our funded research projects has just been launched on blood.ca. Together with our publications database, research highlights, links to this blog, research units and other news, you’ll discover a knowledge hub for the transfusion and transplantation community.  
 

Blood and transfusion research has a long history: from the early days of transfusion medicine to military initiatives that deliver much-needed transfusion to the battlefield to that closer-to-home research that enables advances in patient care, increases clinical knowledge and enhances blood safety.

Canadian Blood Services supports world-class, mission-driven innovation through its researchers and collaborative networks. Exploratory and applied studies uncover new information to develop best practices in transfusion and transplantation medicine. 

For those curious about this work, you can find out a bit more about the research that goes on behind the scenes. Research Units are an excellent resource, and this blog, celebrating one year of research, education and discovery stories is also a great place to start. Here’s a roundup of a few research stories from the last year.

 

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Safety matters

It’s important that blood products used in treatment don’t make the recipient’s condition worse, either through adverse reactions or infection. It’s also important not to cause harm to the donor. The following studies involving Canadian Blood Services researchers are examples of how research aims to make transfusion safer for everyone.

  • Curious about the effect of storage on blood products, researchers looked at the effect that different plasticizers had on red blood cells. They compared storage bags made with different materials and found the best combination for storing red blood cells for safe transfusion.  
  • Blood operators rely on many safeguards to prevent contaminated blood from reaching transfusion patients and to protect the health of donors. Implementing screening questionnaires for donors at the point of collection and filtering out white blood cells are among the steps taken. Ongoing research keeps processes and procedures efficient and effective.
  • Researchers found that Dengue, a mosquito-borne virus could hide away and multiply in platelets during storage. Operators use research like this inform how to protect against known and emerging pathogens.
  • Donor safety is also top of mind. A recent study found that some donors have low levels of ferritin, a blood protein marker of the body’s iron stores. Ferritin levels also predicted an inability to donate in the future due to reduced hemoglobin. To help donors stay healthy, study participants with low ferritin levels were advised to visit their doctor for further investigation. Based on this research, eligbility requirements for donors were changed. 

Efficiency matters

Blood components are tricky materials to store safely and effectively after collection. Research on improving storage conditions and extending shelf life helps reduce waste and maximize the supply without compromising patient safety

Innovation matters

Innovation requires research, and developing best practices and introducing new equipment require thorough evaluation for safety, efficiency and benefit. Blood donated to netCAD is often used to test out new equipment. It can also go to researchers investigating new treatments or developing new tools. 

  • Adding new, closed-system cell-washing equipment into red blood cell treatment protocols extended product storage time and improved treatment effectiveness for patient safety.  
  • Researchers developed ThromboLUX, a laser device that uses light and Doppler shift characteristics to scan units for platelet quality. Easy to use, it can monitor platelets at production, or be used at the bedside to help clinicians choose the most suitable product for patients.
  • Megakaryocytes, which produce platelets, are useful in blood research. However, they are difficult to source and grow in the lab. Producing them from a human peripheral blood source would make studying them much easier.
  • To help patients requiring intravenous immunoglobulin (IVIg), a plasma protein drug used to treat immune disorders, researchers are developing a test, called the monocyte monolayer assay, to help identify patients at risk of IVIg-associated hemolysis. 
  • On the transplant side, the Canadian cPRA Calculator, a recent innovation by a team of Canadian Blood Services researchers and the National HLA Advisory Committee, improved the situation for Canadian transplant patients.

Want to read more?

Stay tuned as we put this first year of sharing research behind us and prepare for more research, education and discovery…

 
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A primer on platelets


Wednesday, January 11, 2017

Blood is red. That’s because of the red blood cells or erythrocytes that whizz around your veins and arteries. The colour is a great visual marker, both clinically and emotionally, but sometimes its very redness hides the other important components that are in you to give. These include plasma, the straw-coloured liquid that carries red blood cells, white cells (leukocytes), other important molecules such as albumin, antibodies and coagulation factors, and tiny fragmentary cells called platelets.

 

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What are platelets?

Platelets, or thrombocytes, are spherical cells (shaped like "plates"), much smaller than red or white blood cells. They come from megakaryocytes in the bone marrow, which release these tiny cell fragments into the blood stream every single day. An average adult makes around 1011 platelets on a daily basis to keep levels high enough for efficient blood clotting.

Yes — that’s 100 billion every day — why so many?  Platelets are important for fixing the wear and tear our blood vessels experience every day. However, since platelets lack a nucleus, they only live for around 10 days in circulation, or up to 36 hours stored in the spleen. Hence, the constant production mode.

Why platelets? What do they do?

Platelets are an important part of hemostasis (stopping the flow of blood), which prevents you from losing too much blood when a vessel wall is damaged. Platelets help the blood clotting process (or coagulation) by gathering at the site of an injury, sticking to the exposed lining of the blood vessel, and creating a platform on which a clot can form.

 

 

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Who needs platelets?

Patients with low platelet numbers (thrombocytopenia) can develop clotting deficiencies. Low platelet numbers occur if conditions either interfere with their production or accelerate their loss; severe bleeding such as from a road traffic accident or other trauma, drugs used in chemotherapy treatment, and even cancer itself are the most common reasons for this. Less commonly, conditions such as viral and bacterial infections, immune-mediated destruction, where a patient’s own antibodies attack platelets by mistake, or rare instances where the platelets created are faulty and cannot clot, also interfere with hemostasis. 

Supply and Demand

Since low platelet numbers, through disease or drug treatments, trauma or surgery, compromise the clotting process and is potentially life threatening, patients often need a prompt infusion of donated platelets.

…and this is where donors come in.

Canadian Blood Services collects platelets from whole blood donations (by separating out the different components: red blood cells, plasma and platelets) and through apheresis donations.

Collection from a single donor, through apheresis, is very similar to regular whole blood donation, in that a cannula in your arm vein draws blood into a collection bag. However, instead of keeping all the components, only the platelets are retained. A centrifugation step separates the platelets from the rest, which then returns to the donor via the apheresis machine.  For this reason, a platelet donation takes a little longer, around 90 minutes depending on the donor’s platelet levels but it can be repeated every 2 to 4 weeks. 

 

 

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Here a donor's platelets are being collected using the apheresis method. In this method, the apheresis machine is positioned next to the donor to extract his/her platelets and return the rest of their blood to their circulating blood.

Canadian Blood Services also prepares platelets from whole blood collections via a process called buffy coat collection. This process isolates platelets from red blood cells and plasma in a centrifuge at Canadian Blood Services manufacturing sites.

Managing the collection and distribution of platelets is a challenge and regular donation is vital for maintaining an adequate supply. 

 

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Platelets are extremely sensitive and they also need to be stored under gentle agitation to stop them from clumping. Furthermore, they need to be stored at room temperature, and for this reason platelet units are susceptible to bacterial growth. Ongoing research collaborations through the Canadian Blood Service’s research facility, netCAD, and scientists at other institutes are looking at ways to improve storage conditions for platelets to extend their shelf life . For example, platelets are usually stored in plasma; researchers have found that platelet additive solutions, rather than plasma, might be a better buffer for them since it seems to prevent cellular damage.

Other research collaborations look at how the transfusion service can assess platelet quality in storage, to give patients the best possible outcome. Researchers developed ThromboLUX, a laser device that transfusion staff could use to quickly and easily scan units for platelet quality. Using this information, clinicians can then choose the best suitable product to treat the patient in an emergency.

Platelets are in you to give. If you’d like to become a platelet donor, check out the resources below.

 

Further reading:

Donating Platelets

Frequently Asked Questions

Blood for Research: Donating at netCAD

It’s Still In You to Give

A Platelet Podcast: 'Platelets Unplugged: The Sticky Truth, a co-production of the International Collaboration for Transfusion Medicine Guidelines and the AABB​, is the first in a series of ICTMG podcasts digging into best practice for the transfusion medicine community and health-care professionals.


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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Sharing the News: Science Communication for … Scientists


Wednesday, December 21, 2016

Communicating science is an important part of the job for anyone involved in clinical research, whether it takes place face-to-face with the patient, a donor or the wider scientific community. Unfortunately, outreach like this can seem a daunting prospect to the lab scientist and practitioner; it is often easier to hide behind the bench or the stethoscope.

 

 

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So how do you get the message out? Being an expert in a subject is not much use if no one knows what you’re working on, and publication in peer-reviewed journals only reaches your peers unless a national newspaper picks it up. Unless you’re active in the conference circuit or you're the first stop for your local news media, most researchers face limited exposure.

Luckily, there is a way, and it’s not too complicated. Our post below should help get you started over the festive break.

“One survey of scientists found that nearly half of all academic scientists were engaged in some type of outreach and interactions with mainstream media have become a standard expectation…”  From McClain C and Neeley L. 2014

 

Science in 140 characters? 

Social media, especially Twitter, is an excellent way to reach out. Yes, it is possible to get the story out, even in 140 characters. Scientists tweet about anything and everything, including primary research paper publication, news and opinion, jobs, meetings, experiments that go wrong and of course, what they had for breakfast! To get you started, we’ve rounded up some great resources as a holiday reading list below — why not check some of them out for hints and tips on the art of science communication?

Why take the plunge?

First up – what are the benefits? While it might not bump up your citation rate in journals, taking your research to Twitter gets it in front of a wider audience. In addition to forcing you to be brief (maximum 140 characters!), you'll need to ditch the jargon to make your message accessible. It is a great training in science communication for all levels.

  • Networking – Broaden your network among peers, a wider scientific community and curious minds. Also, Yoohoo! local journalists - Guidelines for scientists on communicating with the media from the Social Issues Research Center.
  • Clarity – This is your chance to get the correct story out on your research, or even to clear up misinformation and fight clickbait.
  • Thinking outside the box – reaching a wider audience works both ways; exposure to new subjects could foster some excellent interdisciplinary collaborations as well as give a different angle on your current research.
  • Staying current – with so many researchers and practitioners using social media, it’s a great resource to keep up-to-date within your field.
  • Vanquishing stereotypes! – your chance to defeat the uncommunicative scientist image and give researchers an image make-over.

Nuts and Bolts

Interested? Then let’s get started. The links below give handy hints and tips for beginners.

  • Science Magazine has a useful How To Use Social Media for Science post to help scientists.
  • Paige Jarreau @fromthelabbench, biological engineer turned science communicator, created this handy slideshare and also wrote this post showing how she got started
  • Dr. Navneet Majhail explains more on why twitter is useful for health professionals in hematology in the slideshare below:

 
  • Dr. Mike Thompson shares his thoughts in a #EBMT16 (European Society for Blood and Bone Marrow Transplantation) presentation: Social Media in Hematology / Oncology / BMT

And to round things off, the American Association for the Advancement of Science (AAAS) has a handy primer on communicating science online. You may want to bookmark this site for further resources.

Getting Started

Sometimes the best education is to watch and learn; here are just a few Tweeps to follow:

@bloodbankguy (Joe Chaffin, MD), a pathologist and transfusion medicine specialist, tweets regularly. Tweets feature transfusion medicine content on his website, which includes quizzes, podcasts and blog posts on multiple areas of transfusion medicine and blood banking.

@KatePendry, who is a Clinical Director in Patient Blood Management, and NHS Blood and Transplant, for the United Kingdom’s National Health Service (NHS) as well as a Consultant Haematologist, tweets a wide spectrum of blood-related content. She often shares content from other clinical researchers in the field.

@TransfusionWM (Dr. Suzy Morton), also in NHS Blood and Transplant work, regularly shares current research in transfusion medicine.     

@Gogmum (Dr. Sylvia Benjamin) is a senior lecturer at Oxford University who tweets about blood, sharing most recently coverage of the American Society of Hematology #ASH16 conference.

@TeamHaem is an educational group from Newcastle-upon-Tyne in the UK, with a number of individuals collectively tweeting out educational resources and updates. It is also a great aggregation of useful resources.

@Frank_Dor is a transplant surgeon at Hammersmith Hospital in London, UK who shares science and research updates while maintaining an active network among the transplantation social media community.

@CaulfieldTim is a professor of health law and science policy at the University of Alberta.  

@JeannieCallum is a Canadian expert in transfusion reactions and director of the blood and tissue bank at Sunnybrook Health Sciences Centre.

@dryulialin is a transfusion medicine physician and hematologist. She tweets about transfusion quality improvement, physician education and patient blood management. 

@ESaidenberg is a hematologist at The Ottawa Hospital.

Many national and international organizations involved in hematology, transfusion medicine and transplantation science run active social media accounts. Many of them share as-it-happens conference news, which is a boon if you cannot attend, as well as recent research, member education opportunities and other information that is useful to hematology and transplantation professionals.

@ASH_hematology The American Society of Hematology tweets out research as well as promoting journal articles from @BloodJournal

@BritSocHaem The British Society of Haematology, whose website also contains a library of useful diagnostic images 

@CanadasLifeline Canadian Blood Services tweets out mainly donor updates, but does include research news and transfusion medicine information in its twitter stream.

@redcrossbloodau The Australian Red Cross’s blood ‘arm’ tweets out donor news and transfusion research.

@TransfusionLib is the social media account of the Transfusion Evidence Library, a digital repository of evidence-based information on transfusion research. The website is supported by the UK Blood Services and contains a fully searchable aggregation of reviews; content is endorsed by the Cochrane Collaboration.

@TransplantJrnl shares updates and research published in Transplantation.

@transplantev is a Centre for Evidence in Transplantation based in the UK, sharing research news, matters of interest and updates for the transplantation community.

@CNTRP Canadian National Transplant Research Program platform to improve donation; extend the longevity of grafts; and improve survival and quality of life for transplant patients.

Hashtagged?

The hashtag is a powerful symbol, and on social media, it’s a great way of directing your news or finding content. For transfusion and transplantation medicine, the following hashtags are the ones to follow and of course, to tag your tweets once you get started. Check out this handy reference to find more healthcare-related content. 

#blooducation#transfusion#bloodsci#hematology#Haematology#transplantation#organdonation

Get tweeting!

Hiding behind the bench or the stethoscope is no longer an option for scientists these days. In addition to sharing the knowledge within our own research communities, we also need to encourage public interest. Not only is outreach a great tool for reaching potential transplantation and transfusion donors, a well-educated public is also able to make informed choices on personal medical issues and influence broader policy decisions.  Now more than ever, it is important to get out into the world and talk about your work—preferably without a cloud of jargon to get in the way.

What’s stopping you? Get tweeting!

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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It’s still in you to give: donating blood for research in Vancouver


Wednesday, October 19, 2016

“It’s in you to give" is the fantastically simple call to action from Canadian Blood Services. But for some people — such as those of us with a mixed bag of travel and medical histories — it isn’t so easy to just show up, roll up (a sleeve) and then settle back as this life-giving liquid flows into the collection bag.

Blood collected through regular donations goes to patients who need blood products to manage a wide variety of health concerns. Recipients are already dealing with serious medical issues, and the last thing they need is added risk from a transfusion. For this reason, Canadian Blood Services is hyper-vigilant about protecting recipients by ensuring the high quality of its products.

The safety of the blood supply managed partly by screening, whereby donations are delayed or prevented due to a variety of risk factors. These include recent travel to active hot spots for infections such as malaria and Zika virus, potential exposure to pathogens, and existing medical conditions such as cancer. Find out if you’re able to donate by taking this short quiz.

For many prospective donors, this screening can mean a lifetime ban on donating blood. But for some, there is another way to help. If you live in or around Vancouver, it is still possible to roll up a sleeve, but this time for research. Your blood can make a difference!

It’s still in you to give

There is no suitable biological substitute for the red stuff. So how do Canadian Blood Services and clinical researchers test out new equipment and processing workflows or investigate transfusion science?

This is where Canadian Blood Services' Blood for Research donor clinic in Vancouver comes in. It’s set up just like a regular donation clinic, but it accepts blood from some people who are not eligible through the regular donation program. This is a truly unique facility established by Canadian Blood Services in 2002. Here they collect and process donations to support the design, development and validation of new products and processes. They also distribute products for research to scientists and other specialists who need blood for discovery research.

 

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We runs a fully equipped laboratory and processing facility on site. This is also where equipment is tested, using blood donated in the onsite clinic. 

 

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How do I get started?

First, check out the eligibility requirements for regular donation. These change frequently as Canadian Blood Services gets new information from transfusion science. If you find that, like me, a cancer survivor [Note that not all cancers result in a lifetime donation ban!] and a former resident of the United Kingdom, you are indeed ineligible for regular donation, then head over to check your blood for research eligibility.

From here, making an appointment is easy. Although it’s possible to drop in, the blood for research clinic is often fully booked, so it’s best to either email or phone to set up a date and time. The clinic will send you a reminder a week before, with information on location, parking and how to prepare yourself for giving blood: with a good night’s sleep, and by staying hydrated and eating a suitable meal.

A welcome sign at the door. The blood for research clinic is easy to find, and directions are included in the welcome email you’ll receive before your appointment.

 

On the day

Just like in regular blood collection clinics, the blood for research clinic is proactive about donor safety. In addition to standard testing (hemoglobin levels, blood pressure and body temperature) on the day of donation, all donors must complete a standard health questionnaire that flags potential areas of concern. If clinic staff cannot ensure that there is no risk to you, they will delay collection until a medical advisor has cleared you.

 

 

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A tiny blood sample by finger prick is taken to check for hemoglobin levels before donation. Many donors say the finger prick test at the beginning of the appointment is the most painful part of the whole procedure. It is — the rest is easy!

In addition to health screening, 'blood for research' donors have an extra step to confirm consent. Before donating, you will be asked for consent to use and bank your blood for current and future research projects, and you may even opt out of specific research areas,  if you so wish.

Then all you need to do is settle back on the couch and let staff expertly guide you through the donation process. You won’t find any differences in procedure from this point onward, since staff use the same blood collection tubing and bags as in the regular donation clinics.

 

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Blood donation in progress, with blood flowing through the tube from patient to blood bag. 
​Nothing unusual is going on here: You’ll find all the same bags, tubes and monitoring equipment used in a regular donation clinic.

Collection takes around 15 minutes. Once it’s over, expect to stay on site for 10 to 15 minutes relaxing over a coffee, hot chocolate or juice, and cookies. Did I mention that parking and transit costs are covered too?

 

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It’s still in ME to give! Whoopee! A blood donor once again, with a snazzy bandage to prove it. 

Want to come back? As with regular donations, you must wait a minimum of 56 days (or longer) between visits. 

 

Blood for Research clinic location and details:

University Marketplace (at UBC)
207-2150 Western Parkway
Vancouver, BC V6T 1V6

researchdonations@blood.ca

(604) 221-5515

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.

 

The opinions reflected in this post are those of the author(s) and do not necessarily reflect the opinions of Canadian Blood Services.

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The __Cs _f ___ _l__d Types


Wednesday, August 17, 2016

A #missingtype repost of "The ABCs of ABO Blood Types".

If the letters A, B and O went missing in everyday life, it would be difficult to understand the world around us. When we are missing the blood groups or types that the letters A, B and O represent, it becomes difficult to treat critically ill hospital patients and save lives. Blood type is one way we are all connected and this post, originally published during National Blood Donor Week in June, digs into the science and history behind ABO. 

A brief history of ABO

In the early days of transfusion medicine, doctors gave patients all sorts of different fluids, including blood or milk from animals. Success varied, and the results were often disastrous—even when they used human blood. 

It wasn’t until the start of the 20th century that physicians learned the ABCs of the ABO blood types and finally understood how to give a successful transfusion.

Before learning about blood types, doctors noticed that mixing blood samples from patient and donor sometimes caused clumping, or agglutination. They also noticed that transfusion could destroy the patient’s blood cells. But they usually dismissed these findings, explaining them as a part of the illness.

In 1901, Austrian doctor Karl Landsteiner decided to find out more. When he mixed red blood cells (erythrocytes) from one person with the serum, the fluid that remains after blood clots, from another, he noticed that it didn’t always clump.

Karl Landsteiner, 1920s.

With further testing, he found he could divide people into one of three groups—A, B and O (initially called C)—according to these clumping reactions. A year later, his colleagues DeCastello and Sturli added a fourth grouping, or blood type: AB.

Landsteiner, with his knowledge of immunology, proposed that the agglutination was an allergic reaction. The different blood groups were caused by antigens, or surface markers on the red blood cells. People’s immune systems created antibodies, anti-A and anti-B, against the blood type they didn’t have. When different blood types were mixed together, the antibodies bound to the surface markers on the cells, making them clump together.

Blood Types and Antigens

And Dr. Landsteiner was right. The blood type antigens are carbohydrate chains attached to glycoproteins on the red cell surface. Each of the blood types A and B carries one of two different carbohydrate chains, while type AB carries both types of chain and type O carries neither.

Furthermore, individual people make antibodies in serum against the type that they don’t carry. When red cells from a type A person are transfused into a type B person, anti-A antibodies recognize the cells as foreign and destroy them.

The same thing happens if type B blood cells are transfused into a type A person. Since type O blood does not have A or B markers, these cells can be transfused into all patients, since they they don’t cause a reaction. That’s why type O donors are described as “universal donors.” Correspondingly, type AB patients are “universal recipients”: they can receive all types of blood.

 

ABO Blood Type Matching Chart

Plasma transfusions follow the opposite rules, since it is the fluid part of blood that carries the antibodies. As with red blood cells, transfusing plasma from a type A individual into a type B patient is not possible, since the anti-B antibodies would attack the recipient’s red cells—and vice versa. But type AB patients can only receive plasma from type AB donors, whereas type O patients can receive plasma from anyone.

 

Antibodies in plasma

Although ABO is the most important blood type system for transfusion medicine, clinicians need to be aware of other cell-surface antigen markers. Rhesus factor, also discovered by Landsteiner in collaboration with colleague Alexander Wiener, is a protein that spans the red cell membrane.

Most people are rhesus positive (Rh+). However, it is important to know rhesus status in transfusion medicine, especially for sensitized people and during pregnancy. In these cases, anti-rhesus antibodies will destroy red cells. During pregnancy, the antibodies cross the placenta and cause anemia in the developing child.

 

ABO rh Blood Types

There are approximately 35 different blood groups in human beings, but the ABO and Rh systems are the most commonly encountered. These two are the most important in transfusion medicine. Doctors must pay attention to the ABCs of ABO by cross-matching to check for agglutination before a transfusion to make sure that the blood products will not harm the patient.

Right now, As, Bs and Os are missing in Canada. This means more people need to come forward and register their intent to donate blood this year at missingtype.ca

 

Further reading:

missingtype.ca

The facts about whole blood

Karl Landsteiner’s 148th birthday (June 14, 2016 - Google Doodle) 

 

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.


 

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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The ABCs of ABO Blood Types


Tuesday, June 14, 2016

It's National Blood Donor Week and we're celebrating blood donors from across the country who make a lifesaving difference to patients in need. Each of us has the right blood type to give life: ABOAB. This acronym refers to  four blood groups — A, B, AB, and O. Blood type is one way we are all connected and today's post digs into the science and history behind ABO.

By Amanda Maxwell

In the early days of transfusion medicine, doctors gave patients all sorts of different fluids, including blood or milk from animals. Success varied, and the results were often disastrous—even when they used human blood. 

It wasn’t until the start of the 20th century that physicians learned the ABCs of the ABO blood types and finally understood how to give a successful transfusion.

Before learning about blood types, doctors noticed that mixing blood samples from patient and donor sometimes caused clumping, or agglutination. They also noticed that transfusion could destroy the patient’s blood cells. But they usually dismissed these findings, explaining them as a part of the illness.

In 1901, Austrian doctor Karl Landsteiner decided to find out more. When he mixed red blood cells (erythrocytes) from one person with the serum, the fluid that remains after blood clots, from another, he noticed that it didn’t always clump.

Karl Landsteiner, 1920s.

[ii]

With further testing, he found he could divide people into one of three groups—A, B and O (initially called C)—according to these clumping reactions. A year later, his colleagues DeCastello and Sturli added a fourth grouping, or blood type: AB.

Landsteiner, with his knowledge of immunology, proposed that the agglutination was an allergic reaction. The different blood groups were caused by antigens, or surface markers on the red blood cells. People’s immune systems created antibodies, anti-A and anti-B, against the blood type they didn’t have. When different blood types were mixed together, the antibodies bound to the surface markers on the cells, making them clump together.

 

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And Dr. Landsteiner was right. The blood type antigens are carbohydrate chains attached to glycoproteins on the red cell surface. Each of the blood types A and B carries one of two different carbohydrate chains, while type AB carries both types of chain and type O carries neither. Furthermore, individual people make antibodies in serum against the type that they don’t carry. When red cells from a type A person are transfused into a type B person, anti-A antibodies recognize the cells as foreign and destroy them.

The same thing happens if type B blood cells are transfused into a type A person. Since type O blood does not have A or B markers, these cells can be transfused into all patients, since they they don’t cause a reaction. That’s why type O donors are described as “universal donors.” Correspondingly, type AB patients are “universal recipients”: they can receive all types of blood.

 

 

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Plasma transfusions follow the opposite rules, since it is the fluid part of blood that carries the antibodies. As with red blood cells, transfusing plasma from a type A individual into a type B patient is not possible, since the anti-B antibodies would attack the recipient’s red cells—and vice versa. But type AB patients can only receive plasma from type AB donors, whereas type O patients can receive plasma from anyone.

 

 

Thumbnail

Although ABO is the most important blood type system for transfusion medicine, clinicians need to be aware of other cell-surface antigen markers. Rhesus factor, also discovered by Landsteiner in collaboration with colleague Alexander Wiener, is a protein that spans the red cell membrane.

Most people are rhesus positive (Rh+). However, it is important to know rhesus status in transfusion medicine, especially for sensitized people and during pregnancy. In these cases, anti-rhesus antibodies will destroy red cells. During pregnancy, the antibodies cross the placenta and cause anemia in the developing child.

 

 

Thumbnail

There are approximately 35 different blood groups in human beings, but the ABO and Rh systems are the most commonly encountered. These two are the most important in transfusion medicine. Doctors must pay attention to the ABCs of ABO by cross-matching to check for agglutination before a transfusion to make sure that the blood products will not harm the patient.

 

Further reading:

What is ABOAB?

The facts about whole blood

Karl Landsteiner’s 148th birthday (June 14, 2016 - Google Doodle) 

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.


About the author

Amanda Maxwell is the lead science writer at Vancouver-based Talk Science to Me. 

 

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.

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Why do scientists use mice in medical research?


Wednesday, June 01, 2016

By Amanda Maxwell

“The mouse is the only mammal that provides such a rich resource of genetic diversity coupled with the potential for extensive genome manipulation, and is therefore a powerful application for modelling human disease.”—Justice et al. (2011)

Animal research is an emotional subject, inspiring passionate debate on both sides. Although some find it uncomfortable to think about, it’s important to understand why animals like mice are used for medical science.

Mice fill a special and important role in medical research. Like humans, mice are mammals, and their bodies undergo many similar processes, such as ageing, and have similar immune responses to infection and disease. Their hormone (endocrine) systems are a lot like ours, too. They’re also one of the first species — along with humans — to have had their complete genome sequenced. From this, we’ve learned they share approximately 80 per cent of their genes with us. 

Last month,  Centre for Innovation Scientist Dr. Donald Branch along with the University of Toronto’s Dr. Anton Neschadim published a new model “Mouse models for immune-mediated platelet destruction or immune thrombocytopenia” in Current Protocols.

 

Many important breakthroughs in medical science have come from studies carried out in mice. These include treatment for acute promyelocytic leukemia — a form of blood cancer that affects young adults and is now one of the most treatable forms of the disease — as well as gene transfer protocols for cystic fibrosis, which are currently being tested.

Nobel-winning scientific achievements such as the discovery of vitamin K, the development of the polio vaccine, the invention of monoclonal antibody technology now used for cancer treatment, and the unravelling of how neurons talk with each other in the brain all would not have occurred without mice.

Missing in action: Some of what medical science would be missing if not for research in mice

  • Development of protein conjugate vaccines and testing in mice helped improve the meningitis Hib (Haemophilus influenzae type b) vaccination for young children.
  • Without testing in mice to show its role in blocking hormone action, the drug tamoxifen would not be available to women as a treatment for and prevention against breast cancer.
  • Recent research in mice carrying a humanized immune system has uncovered potential new targets for a novel tuberculosis vaccine

 

Why are animals still used for clinical research?

Although advances in laboratory technology offer alternatives such as cell and organoid culture (3D mini-clusters of cells that behave like tiny organs) for clinical research, scientists still gain a lot of valuable information from working with laboratory animals such as mice.

What happens in a living body cannot be investigated using a dish of cells, for example. Often disease involves more than just a single organ, and to test new drugs, we must look at a whole body to see how it responds to therapy.

Researchers use many other systems for clinical investigation — such as cell culture, explants, spheroids, in silico modeling and organ culture—but a mouse offers what these alternatives cannot: a whole, living organism in which to investigate disease, response to treatment, development of cancer and other basic research questions.

 

Why Mice? Physiology

The physiology and size of mice — they’re small enough to handle and house easily — are the main reasons for their popularity in the lab. In 2013, labs in Canada used just over 1.2 million mice in research according to the Canadian Council for Animal Care, the national body that oversees the strict regulations surrounding health and welfare for all laboratory species.
(CAC Animal Data Report 2013)

Physiologically, mice are very like humans, albeit around 3,000 times smaller (Partridge, 2013) but with similar basic body functions such as blood cell production (haematopoiesis), digestion, respiration and the cardiovascular system. Although differences do exist, mice respond similarly to humans when they are sick or undergo treatment.

For example, through work in mice, researchers recently made advances in treating the blood disease immune-mediated thrombocytopenia, an autoimmune disease where the body makes antibodies that target platelets for destruction before they can be used for blood clotting (Neschadim and Branch, 2015; Yu et al. 2015). In another study, tests in mice with another type of coagulation disorder showed how proteins in a plasma transfusion restore clotting function and stop bleeding (Eltringham-Smith et al., 2015).

“Mouse models of various human diseases, including immune thrombocytopenia, have been relatively easy to develop, since mouse physiology and metabolism resemble those of humans. These models have been extremely valuable to me and my team for investigating ITP. Without them, we would not be as far forward in our research, looking for drugs that could help improve life quality for many patients. We've just published detailed methods on how to set up and use mouse models for ITP.  One model, our dose-escalation mouse model, more closely resembles human ITP than most other models currently in use by investigators."

                                        — Dr. Donald R. Branch, PhD, scientist, Centre for Innovation, Canadian Blood Services

Why Mice? Breeding and species diversity

Mice also breed easily, with short pregnancies and large litter sizes that are important in helping researchers create their own modified mice. However, most laboratories in Canada source non-specialized mice from commercial breeders, receiving purpose-bred animals with a full breeding history. For researchers, this is very important: Working with animals that show very little difference among individuals increases the value of experimental results, since all the animals respond the same. For even more consistency, we've also been able to clone mice since 1997

On the other hand, mice are also extremely diverse, meaning that commercial breeders can select for individual traits to create inbred strains with unique characteristics. For example, the CBA mouse has a low incidence of mammary tumour (breast cancer) development, whereas the BALB/c nude mouse is immunodeficient, since it lacks a thymus. These kinds of breed-specific properties are useful, as they allow scientists to focus on specific diseases. Researchers choose mdx mice, lacking mature dystrophin muscle protein, as models for studying Duchenne Muscular Dystrophy, while others choose non-obese diabetic (or NOD) mice as good models to study new treatments for autoimmunity (Wang et al. 2015).

Why Mice? Genomic modification

In addition to breeding strategies based on natural variations, researchers also have a number of genetic modification tools available. Since mice share approximately 80 per cent of their genes with humans, modifying mouse DNA is a powerful method for creating animal models of human disease. Techniques such as the Cre/lox system and the newer CRISPR gene editing tool allow researchers to delete, activate or repair genes (Long, et al. 2016), thus recreating human disease in the mouse or examining what happens when they correct a mutation.

Removing or inactivating a gene creates what scientists call a “knock-out” mouse. Alternatively, they can create transgenic animals by making the mice express human genes or carry human cells—or even tissues.  With techniques like these, researchers can create “humanized” mice that respond physiologically almost like us, letting researchers look at the way disease changes a human body and how it responds to treatment. Researchers carry out important work on HIV infection and its treatment using mice with humanized immune systems (Schultz et al., 2012). They’ve also tested out new therapies that prevent Rhesus-negative mothers from becoming sensitized to Rhesus factor during pregnancy, using HOD mice that express a red blood cell–specific recombinant protein (Bernardo et al., 2015).

Even though there are key differences between the mouse and human genomes, those differences aren’t enough to discount the value of mice to the study of human disease. Although regulatory elements might be in different places, shuffled around in the 75 million years since mouse and human evolution parted, their basic functions are preserved

 

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About the mouse...

Animal researchers are constantly mindful of the three Rs

  • Replace: Is there an alternative experiment that doesn't need animals?
  • Reduce: Can we adjust the experimental design to use fewer animals?
  • Refine: Can we minimize the impact of the experiment on the animals?

Animal research is tightly regulated in Canada, with strict controls and oversight in place to ensure welfare and ethical treatment. These regulations cover housing, environmental enrichment, use of medications and anaesthesia, and even breeding of genetically modified mice. Researchers must first present their experimental proposals to local and federal committees to establish an animal care plan and assess factors such as severity, design and scientific value before going ahead with studies. 

Penicillin, originally discovered by Alexander Fleming in 1928, did not appear as a lifesaving medical treatment until the work of Howard Florey, who tested its safety and efficacy in mice over ten years later.  Without mice (and other animals) in research, human and animal medicine would be without penicillin, vaccines for polio and meningitis, monoclonal antibody therapy, a cure for acute promyelocytic leukemia, and gene transfer for cystic fibrosis. 

 

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Why Mice? Irreplaceable 

Scientists are always looking for alternatives to the use of animals in clinical research, but the role of mice as experimental models for human disease is, as yet, irreplaceable. Even with differences between the two species, carrying out basic research in humanized mouse models of disease gives scientists valuable information. Using mice as surrogates allows researchers to first see how patients might respond to treatment before giving them the drug — a vital step in ensuring patient safety.  

 


Canadian Blood Services – Driving world-class innovation

Through discovery, development and applied research, Canadian Blood Services drives world-class innovation in blood transfusion, cellular therapy and transplantation—bringing clarity and insight to an increasingly complex healthcare future. Our dedicated research team and extended network of partners engage in exploratory and applied research to create new knowledge, inform and enhance best practices, contribute to the development of new services and technologies, and build capacity through training and collaboration.


About the author

Amanda Maxwell is the lead science writer at Vancouver-based Talk Science to Me. 

 

The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.
 
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