1. Blood 101 Hank Hanna, MD Medical Director American Red Cross Pacific Northwest

2. Objectives Become familiar with the Donation Process Understand the components of whole blood and how they are processed and modified. Understand testing on donor units. Know the indications for RBC, Plasma, Cryoprecipitate and Platelet Transfusion. Recognize various types of transfusion reactions. Become aware of alternatives to transfusions. 2

3. Background Every two seconds, someone in the US needs a blood transfusion. Across the nation, the Red Cross collects approximately 5.3 million pints of blood from 3.1 million volunteer donors annually. These blood donations are then processed into >7.7 million blood products. Regionally we collect 250,000 pints of blood each year. We serve 60 hospitals in OR and WA Regulated by: FDA, AABB, CMS(CLIA), FACT 3

4. Donation Process Health History Questionnaire Physical Ways to Donate 4

5. Donation Process Screening – required by FDA in order to maintain a safe blood supply. Behavioral Physical 5

6. Health History Questionnaire Addresses behavioral part of screening Most blood facilities use a Health History Questionnaire All allogenenic donors must answer these questions. Sexual Behavior IV Drug Use Travel History Living Conditions Medications – Rx and OTC Current Health State 6

7. Physical Vital Signs Heart Rate – 50-100 bpm Temp - ≤37.5ºC per FDA Blood Pressure – 180/100 Hemoglobin - ≥12.5 g/dL per FDA 12.0 g/dL for women is under consideration 7

8. Ways to Donate Whole Blood RBC, plasma, cryo Time: approx. 5 min. Donation Interval: every 8 weeks Apheresis Double RBC, plasma, platelets, cryo Time: approx. 45-90 min. depending on product Donation Interval Double RBC 16 weeks Plasma every 4 weeks Platelets every 2 days but no more than 2x/7 days and 24x/year 8

9. Component Processing Whole Blood Apheresis Component Modification 9

10. Whole Blood Processing Processed after donation RBC, plasma and cryoprecipitate Usually occurs within 8 hours of collection Centrifuged to separate red cells from plasma/cryoprecipitate Plasma moved into separate bag and then frozen to -18ºC Plasma thawed to precipitate cryoglobulins, centrifuged and pushed into satellite bag Plasma and Cryo stored at -18ºC for 1 year RBC’s leukoreduced and then stored at 1-6ºC for 42 days 10

11. Apheresis Processing Components separated time of collection Whole blood removed from vein into spinning pheresis bag Spin creates gradients of RBC, platelets and plasma Exit tubes at various levels for each component Open the exit tube for desired component, drains to collection bag Rest is returned to donor Double arm and single arm Platelets stored at RT for 5 days 11

12. Component Modification - Leukoreduction RBC are allowed to pass through WBC reducing filter (<5.0x10 6 WBC) Performed to reduce CMV transmission Febrile transfusion reactions and HLA alloimmunization. Seronegative CMV vs Leukoreduction 12

13. Component Modification - Irradiation Inactivates lymphocytes to prevent TA-GVHD RBCs are exposed to gamma or x-irradiation Changes expiration of RBC to 28 days. Indications IUT, infants who have received IUT Cellular immunodeficiency Neonatal exchange transfusions Granulocyte transfusion Components from blood relatives 13

14. Donor Unit Testing Disease Serologic 14

15. Disease Testing Prevents disease transmission Hepatitis B Hepatitis C HIV-1,-2 HTLV I/II Syphilis WNV Chagas Bacteria (platelets only) 15

16. Serologic Testing ABO D Antigen(Rh) Weak D Antigen Antibody Screen 16

17. Transfusion Recipient Testing RBC Plasma Cryoprecipitate Platelets 17

18. Recipient Testing Type and Screen ABO D Antigen Weak D Antigen Antibody Screen Must have a sensitizing event (previous transfusion or pregnancy) and be negative for those specific antigens Rh, Kell most common Donor compatibility (Crossmatch) Donor RBCs Platelets 18

19. Blood Group Compatibility 19

20. Blood Group Compatibility 20

21. Blood Types and the Population 21 CaucasiansAfrican American HispanicAsian O +37%47%53%39% O -8%4% 1% A +33%24%29%27% A -7%2% 0.5% B +9%18%9%25% B -2%1% 0.4% AB +3%4%2%7% AB -1%0.3%0.2%0.1%

22. RBC Indications Symptomatic Anemia Red Cell Exchange Exchange Transfusion No "Magic Number" Contraindications Anemia that can be corrected with a non-transfusion therapy. Increasing blood volume To improve wound healing 22

23. Plasma Indications Active bleeding or risk of bleeding due to deficiency of multiple coagulation factors or a single factor for which no concentrate is available. Severe bleeding due to warfarin or urgent reversal of warfarin effect. Massive transfusion TTP Contraindications Increasing blood volume or albumin concentration. Coagulopathy that can be corrected with Vitamin K. Normalizing abnormal coagulation results in the absence of bleeding. 23

24. Cryoprecipitate Indications Source of fibrinogen Massive transfusion Plasmapheresis Contraindications Do not use for specific factor deficiencies for which a concentrate is available. 24

25. Platelets Indications Bleeding due to decreased or functionally abnormal platelets. Prophylactic: >10,000/mL in stable, non-bleeding patients >20,000/mL in unstable, non-bleeding patients >50,000 in actively bleeding patients or patients undergoing invasive procedures/surgery Contraindications ITP, TTP, HIT, Thrombosis 25

26. Transfusion Reactions Hemolytic – Acute and Delayed Non-Hemolytic 26

27. Transfusion Reactions STOP the transfusion THINK, could it be an AHTR? TREAT patient INITIATE transfusion reaction workup Types Hemolytic: Acute, Delayed Non-Hemolytic: Febrile, Allergic, Volume Overload (TACO), TRALI, Bacterial, TA-GVHD 27

28. Acute Hemolytic Reactions Symptoms: flank or back pain, hematuria, fever, chills, nausea, vomiting, dyspnea, hypotension, renal failure, DIC, IV site pain Cause: most commonly ABO incompatibility Pathophysiology: complement-mediated intravascular hemolysis Potentially Fatal Treatment: discontinuation of transfusion, hydration, intensive patient monitoring 28

29. Delayed Hemolytic Reactions Symptoms: Less severe than AHTRs, fever and chills hours to days after transfusion Cause: immunologic incompatibility not identifiable at time of recipient testing Pathophysiology: RBCs tagged for removal by splenic macrophages Treatment: supportive 29

30. Non-Hemolytic Febrile Symptoms: fever (↑1ºC), chills, malaise Occurrence: 1% of all transfusions Pathophysiology: cytokine release Treatment: stop transfusion, evaluate for hemolysis 30

31. Non-Hemolytic Allergic Symptoms: urticaria Occurrence: About 3% of all transfusions Pathophysiology: recipient antibodies against donor plasma proteins Treatment: antihistamines, may continue transfusion after resolution of symptoms 31

32. Non-Hemolytic Volume Overload (TACO) Symptoms: dyspnea, cough, hypertension, tachycardia Occurrence: <1% of transfusions. More common in elderly, pre-existing cardiovascular disease Pathophysiology: inability of circulation to handle transfused fluid volume Treatment: oxygen, diuretics, supportive care 32

33. Transfusion Associated Lung Injury (TRALI) Symptoms: hypoxemia, respiratory failure, hypotension, fever, noncardiogenic pulmonary edema, Symptoms arise within 6 hours of transfusion Occurrence: 1 in 5,000 transfusions Pathophysiology: likely caused by donor antibodies to recipient WBC, WBC’s activated by other donor substances Treatment: supportive care(O 2, ventilation), hemodynamic stabilization 33

34. Non-Hemolytic Bacterial/Sepsis Symptoms: severe chills, fever, hypotension, nausea, vomiting Occurrence: rare due to bacterial testing prior to distribution Pathophysiology: endotoxin release Treatment: stop transfusion, culture patient 34

35. Graft-Versus-Host Disease (TA-GVHD) Symptoms: fever, rash, enterocolitis, elevated liver function tests, pancytopenia Occurrence: rare but almost uniformly fatal Pathophysiology: donor lymphocytes mount attack against recipient Prevention: irradiation 35

36. Transfusion Alternatives Hemoglobin Substitutes Perfluorocarbon Emulsions Intravenous Iron (“Bloodless Surgery”) 36

37. Hemoglobin Substitute Mainly consist of free hemoglobin that is unstable and toxic with short half lives due to phagocytosis and RES uptake. Ideal Substitutes: Free of toxicity and side effects Able to uptake O 2 in the lungs and deliver O 2 to tissues Sufficient half life Rapid and harmless excretion Stable at room temperature, easy to store Easy to sterilize Cheap to manufacture No need for compatibility testing 37

38. Perfluorocarbon Emulsions Hydrocarbons with Hs mostly replaced by Fs Dissolve O 2 instead of binding like hemoglobin Have some utility and show more promise than hemoglobin substitutes but can cause progressive hypertension at higher doses, patients may be more predisposed to stroke. 38

39. Intravenous Iron “Bloodless Surgery” Administer Iron and Erythropoietin for several days prior to surgery to stimulate hematopoiesis 39 DayDose 11-2 g IV Iron 2Erythropoietin, Vit B12 3 4 5 6 7 8 9 10Erythropoietin, Vit B12 Surgery

40. Discussion / Questions? 40