9/12/2018

Objectives Great Achievements in Transfusion Medicine 1. Recall major discoveries in the field of transfusion medicine.

Kristin Butler, MLS (ASCP)CM CLPC 2. Describe the evolution of blood banking procedures. Fall 2018

3. Discuss the future of transfusion medicine testing.

First recorded blood The circulation of transfusion attempt blood

• Pope Innocent VIII in 1492 • William Harvey in 1628 • Was given the blood of 10 • Experimentation on animals year old boys • Book, "On the Motion of the • No one survived Heart and Blood in Animals"

First successful blood Harvey’s experiments on circulation transfusion

• Initially on serpents and fish • Richard Lower in 1665 • Tied off the veins and arteries in • Transfused blood from one dog to separate periods of time another • Later on humans using tight ligature on upper arm • Many transfusions were successful ➢Changes to arm above and below ➢Noticed valves in veins

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1st successful human From animal to human transfusion, unpublished

• Jean-Baptiste Denis and Richard • Dr. Phillip Syng Physick in 1795 Lower in 1667 • Successful transfusions from • “Father of American Surgery” lambs to humans • Introduced carbonated water for • After 10 years, this practice was medicinal use in 1807 prohibited • No further studies for 150 years

Blundell’s post-partum transfusions, st 1 successful transfusion, recorded 1825 – 1830

• James Blundell, obstetrician in 1818 • Dr. Blundell performed • For treatment of postpartum hemorrhage 10 more transfusions • Used patient’s husband as donor • 5 were unsuccessful ➢Issues with clotting • Took 4 ounces from the husband using a syringe and injected into wife ➢Fatal reactions

St. George’s Hospital Medical School, Joseph Lister London 1840 and antiseptics

• Samuel Armstrong Lane and Dr. • Promoted using sterile Blundell techniques during surgery • First successful whole blood • Used carbolic acid (coal – transfusion to treat hemophilia tar derivative) to sterilize ➢11-year old George Firmin, post eye surgery • Control infections during ➢6th day post-op, transfused blood from transfusions healthy young woman

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• 1873 – mid-1880s Karl Landsteiner, 1901 Milk • Physicians transfusing milk from • Austrian scientist transfusion cows, goats, and humans • Determined 3 basic blood groups: A, B, C in late • “blood substitute” • C later changed to O (German for Ohne, 1800s meaning nothing) • Saline infusions replace milk in • Experiments with blood from students 1884 • Won Nobel Prize in 1930

Routinely performed by 1903 Landsteiner’s students, 1902

1907: Hektoen suggests improving safety by • DeCastello and Sturli Blood crossmatching transfusions • Determined the AB group in surgery Rueben Ottenberg, NYC: performs first transfusion using type and crossmatch

• These 4 groups what we now know as the ABO blood group system Ottenberg observes Medelian inheritance and describes “universal” utility of group O donors

Universal donor Universal recipient Alexis Carrel, France Carlo Moreschi, Italy • Develops vein-to-vein method of • Forgotten pioneer • Defined by Roger Lee in 1912 transfusion to prevent clotting • Interest in hematology and • Demonstrated that group O blood • Adopted by J.B. Murphy in immunology could be given to all 4 types Chicago • First to understand C’ fixation • Adopted by George Crile in • Demonstrated that group AB could • First describes the antiglobulin receive all 4 types Cleveland reaction • Nobel prize in 1912

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• 1915: Richard Lewisohn uses sodium citrate • Late 1800s: European experiments blood ➢Discovery of Ca2+ role in clotting ➢Changes procedure from direct to indirect ➢Oxalate used in dogs • ➢ 1915: Richard Weil shows feasibility of Production of Ammonium citrate used in dogs Production of refrigerated storage of sodium citrate stored ➢Understanding Ca2+ affinity for citrate blood anticoagulants anticoagulants

➢Beginning 1914: development of • 1916: Francis Rous and J.R. Turner introduced a citrate-glucose solution sodium citrate for human blood ➢Allowed refrigerated storage for several days transfusion ➢Facilitates indirect procedure ➢Allows for establishment of first blood depots

World War I: Establishing hospital and community Western Front 1917 blood banks

• US Army officer Dr. • 1926: British Red Cross – first human blood transfusion service Oswald Robertson • 1932: Leningrad, Russia – first hospital blood depot • First blood depot • 1937: Bernard Fantus, Cook County Hospital in Chicago established ➢First hospital blood bank in the United States • Using blood stored with sodium citrate ➢Originates the term “blood bank” ➢San Francisco, New York, Miami, Cincinnati….

• Philip Levine and R. E. Stetson • Edwin Cohn, Harvard Chem professor described the Rh system in 1939 • Cold ethanol fractionation ➢Mother to stillborn child receives ➢Albumin, gamma globulin, and fibrinogen husband’s blood and suffers severe now available for use reaction ➢Pearl Harbor victims treated with Cohn’s • Karl Landsteiner and Alex Wiener albumin for shock named the Rh system in 1940 ➢Studies using Rhesus monkey • Army Blood Transfusion Service and Depot established ➢Obtained anti-Rh factor ➢Blood type every member ➢Samples from NYC population ➢Donations in the field

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• US Govt establishes nationwide program for blood collection Charles Richard Drew

• “Plasma for Britain” program started • 1st African American to earn doctor of medical science degree • 1st African American to be elected to serve • American Red Cross collects 13 million on the American Board of Surgery • Medical Director of the “Blood for Britain” units of blood by the end of WWI program • Started “bloodmobiles” and localized donation centers • 15,000 whole blood units collected; 5,500 units of plasma

• Acid citrate dextrose (ACD) developed • Coombs, Mourant, and Race use AHG • J.F. Loutit and Patrick Mollison, 1943 to identify “incomplete antibodies”, 1945 ➢Reduce amt of anticoagulant ➢Store greater volumes ➢Longer term storage • American Association of Blood Banks (AABB) is formed in 1947 • Paul Beeson publishes first description of transfusion-transmitted hepatitis, ➢Promote common goals 1943 ➢Blood banking practitioners ➢Development of jaundice months later ➢Blood donors

Single most influential technical development: 1500 hospital blood banks PLATIC COLLECTION BAGS

United 46 community blood centers States, 31 American Red Cross regional 1950 blood centers

Worldwide establishment

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Wartime blood shipment AABB Clearinghouse

• Established in 1953 • Centralized system for exchanging blood among blood banks • Now called the National Blood Exchange

Explosive growth in blood 4400 hospital blood banks use during the 1950s

• Open heart surgery and trauma care United 123 community blood centers • AABB forms Inspection and States, Accreditation committee 55 American Red Cross regional • 1st Edition of AABB Standards 1962 blood centers published • Max Perutz of Cambridge 5 to 6 million units of blood University deciphers the molecular collected per year structure of hemoglobin

All-volunteer blood donor systems Component therapy in the 1960s began in 1970

• Therapeutic plasmapheresis procedure introduced • Careful donor selection and infectious disease testing • Platelet concentrates for cancer patients • Hepatitis B surface antigen (HBsAg) testing began in 1971 • Antihemophilic factor (AHF) concentrates for hemophiliacs ➢Dr. Baruch Blumberg at National Institute of Health (NIH) • Cryoprecipitated AHF methods introduced ➢Developed first test for HBV in 1967 • Rh immune globulin commercially introduced to give Rh(=) women ➢Developed first vaccine for HBV in 1969 • Feasibility of storing platelets at room temp ➢Won Nobel Prize in 1976 for these contributions

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Increasing demand The Era of and blood shortages Transfusion Medicine

• Apheresis being used • Begins in early 1980s frequently • Packed RBCs • Increasing demand plus • Plasma exchange volunteer system • Coagulation products • • Doctors specifically CPDA-1 saves the day! trained in blood transfusion

• 1990: first specific test for HCV • 1981: first AIDS case reported

• 1992: HIV-1 and HIV-2 antibody testing • 1984: HIV identified as cause of AIDS Infectious Infectious • 1996: HIV p24 antigen testing; vCJD identified • 1985: first HIV screening test licensed and disease implemented to protect blood supply disease • 1997: US Govt reports on blood safety – testing in testing in National Blood Data Resource Center founded • 1987: hepatitis B core antibody (anti-HBc) and by AABB the 1980s ALT tests implemented the 1990s • 1992: HCV lookback campaign • 1989: Hepatitis C identified; Human T- Lymphotrophic Virus I antibody testing begins • 1999: nucleic acid amplification testing (NAT)

Where are we now? Blood demand in the U.S today

• >7,000 hospital blood banks and • 36,000 units of RBC blood centers • 10,000 units of plasma • 7,000 units of platelets • >13 million whole blood units collected per year

Source: American Red Cross

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Today’s technology: Today’s technology: AUTOMATION! Replacing tube testing

Gel technology Solid Phase technology

Increasing demands for blood Molecular testing in systems and safety the Blood Bank

• West Nile • RBC genotyping, an alternative to serological typing • Zika • Expression of many clinically • Ebola significant antigens is determined by single nucleotide polymorphisms • Chagas (SNPs) • • Detecting these SNPs can predict the Bacterial contamination red cell phenotype • Maintaining the blood supply • Using donor or patient DNA

Patient DNA + RBC genotyping RBC genotyping primers PCR • Mass screening of donors • Mass screening of donors • When antisera not reliable or • When antisera not reliable or Hybridize to probes available available on microbeads • Detecting weak or variant Ag • Detecting weak or variant Ag Add fluorescent labels • Pregnancy • Pregnancy Analysis of fluorescence emission

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Artificial blood substitutes Artificial blood substitutes

RBC substitutes Synthetic O2 carriers • And the (re)search continues… • Perfluorocarbons (PFCs) • Hemoglobin-based O2 carriers ➢Marine worms in Romania • Dissolve O (HBOCs) 2 ➢RBCs from stem cells in UK and Scotland • Must be mixed with lipid • Recombinant, polymerized Hb emulsion products ➢Human trials are near • Short half life • Derived from humans and animals

The only thing that never changed throughout the years is the importance of blood.

Thanks to these many researchers, we have reached the safe standards that we have today.

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