An Introduction to the Principles of Transfusion Medicine

1. An Introduction to the Principles of Transfusion Medicine Christopher J. Gresens, M.D. VP & Medical Director, Clinical Services BloodSource

2. Principles of Transfusion Medicine Objectives • At the conclusion of this presentation, participants will be able to summarize, from an evidence-based perspective, … • The means by which blood components are manufactured, • The approved uses of RBCs, platelets, plasma & cryoprecipitate, • The standard of care for the use of CMV-seronegative and irradiated “cellular” blood products.

3. Principles of Transfusion Medicine Outline • Brief Historical Perspective • The Manufacture of Blood Components • Evidence-Based Transfusion Indications for: • (Whole Blood) • RBCs • Plasma (including use for major trauma) • Platelets • Cryoprecipitate • Special (CMV-negative and/or Irradiated) Products

4. Principles of Transfusion Medicine A Brief History

5. 1665 — 1st DocumentedAnimal-to-Animal Transfusion Dog-to-dog transfusion by Richard Lower. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

6. 1667—1st DocumentedAnimal-to-Human Transfusion Jean Baptiste Denis infuses 15-year-old boy with lamb’s blood. From Zmijewski’s Immunohematology.

7. 1818—1st DocumentedHuman-to-Human Transfusion Following a 150-year transfusion hiatus, James Blundell transfuses patient with blood from a human donor. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

8. 1800’s—All Manner of Blood Collection Devices Utilized (You think present-day donor centers sometimes face challenges in recruiting repeat blood donors?) From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

9. 1900—ABH Blood Group System ID’d Karl Landsteiner discovers ABH system when he types individuals as (what we now call) group A, group B, and group O. In 1902, his proteges identify a group AB individual for the first time. From Transfusion, Vol. 1, p. 2 (1961)

10. The Discovery of Many OtherRed Cell Antigens Followed • Rh (C, c, D, E, e, …) • Kell (K, k, …) • Kidd (Jka, Jkb, …) • Duffy (Fya, Fyb, …) • MNSs, … • Lewis (Lea, Leb) • … … …

11. Early 1900’s—Getting Blood from Point A to Point B Direct, donor-to-patient anastamosis performed by American surgeon, George Crile. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

12. 1914—Modern Anticoagulation is Born Citrate first used for blood anticoagulation purposes. From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

13. 1939/40—Rh and Cause of HDFN Discovered Levine, Wiener, and colleagues combined their efforts in making these seminal discoveries From Netter Monograph Series

14. 1940’s – Making Plasma Products • Edwin Cohn develops the first fractionation technique to break down the components of plasma into “Cohn fractions.” • John Elliott develops a vacuum bottle/blood container.

15. 1940’s – Making Plasma Products Charles Drew starts the “Blood for Britain” program leading to the manufacture of large quantities of dried plasma. From American Red Cross Museum

16. Blood for Britain (WW II) • Project to collect large amounts of blood in NYC hospitals. • Dried plasma package developed for ease of transport, packaging and storage. • Army-Navy plasma package consisted of 2 tin cans containing 400cc bottles, 1 with distilled water, the other with dried plasma. • Reconstituted in 3 minutes; good for 4 hours.

17. Dried Plasma Packages (WW II)

18. 1950’s and 1960’s • 1953 – Carl Walter and W.P. Murphy, Jr. develop the plastic collection bag. • Around that same time, the refrigerated centrifuge is developed. • Both of the above push transfusion medicine into component production. • 1964 – Plasmapheresis is introduced as a collection method for plasma.

19. But, the importance of ABO supersedes all … From Petz and Swisher’s Clinical Practice of Transfusion Medicine, 2nd ed., 1989.

20. Principles of Transfusion Medicine The Manufacture of Blood Components

21. How We Make Blood Components Collection Process • (1) Via Whole Blood Donation: Whole blood is collected from healthy blood donors into sterile blood bags that contain anticoagulant-preservative. • (2) Via Apheresis: Machines with internal centrifuges separate a donor’s blood into individual components (e.g., platelets, plasma, RBCs, etc.). The desired components are retained, while the remainder is returned to the donor.

22. Donor interview process Finger-stick capillary blood sampling

23. CuSO4 Hemoglobin determination Note: Other methods can also be used for this purpose.

24. BP, Pulse, and Temperature Check

25. The Collection Process Phlebotomy (16 Gauge Needle) Arm Disinfection Prior to Donation

26. The Collection Process Multi-bag whole blood collection kits Flow of whole blood into primary bag

27. Whole Blood Collection

28. Centrifuge (low g forces) WHOLE BLOOD Blood Component Manufacture from Whole Blood (As Done in the USA) RBCs + Platelet-Rich Plasma

29. Centrifuge Used for Component Manufacture

30. Multi-pack Collection Bag

31. Centrifuge - Interior

33. Centrifuge (higher g forces) Platelets + or Plasma Freeze Blood Component Manufacture from Whole Blood • Leukoreduce • Possibly irradiate • Other RBCs + Platelet-Rich Plasma Fresh Frozen Plasma (FFP) or “Plasma Frozen with 24 hours”

34. Thaw (4° C) • Centrifuge Blood Component Manufacture from Whole Blood Fresh Frozen Plasma (FFP) Cryoprecipitate + Cryo-Reduced Plasma

35. Sent for further processing Using the “Leftovers” Wisely Plasma (of any kind) Plasma Derivatives • Albumin • Factor VIII • Immune globulin • etc.

36. Blood can be optimally utilized by the use of specifically required components instead of whole blood… RBC FFP PLT

37. “Shotgun” Approach vs. . .

38. Component Therapy

39. Plasma Platelets Mononuclear Cells Granulocytes Red Blood Cells Whole Blood Whole Blood (vein) (vein) The Principles of Apheresis Anticoagulant added Remaining blood constituents returned Blood constituents separated by centrifuge and selectively collected

40. Caridian BCT Trima Accel

41. Haemonetics PCS-2

42. Plasma Collected Via Apheresis Typically200 mLto800 mL FFP Made from Apheresis

43. Donor sample tubes being readied for testing

44. Infectious Disease Testing (Abbott PRISM)

45. Chagas Disease Testing (Ortho Platform)

46. NAT – HIV, HBV, HCV, and WNV

47. Olympus PK-7200 (ABO, Rh, syphilis)

48. CBC analysis by Pentra XL-80

49. Platelet Bacterial Detection QC Testing by BacT/ALERT

50. Testing • ABO • Rh • RBC Antibody Screen • Infectious Diseases • Syphilis • HBsAg • Anti-HIV-1/2 • Anti-HBc