1. Blood Transfusion Review 2/3/2018
Mahmoud Charif M.D.
Associate Professor of Medicine
Division of Hematology & Oncology
University of Cincinnati College of Medicine

2. Red Cell Antigens Anti-A, Anti-B naturally occurring IgM RH
No need for prior exposure RH
D C E c e A B M N S P U
Lutheran Le
Diego
Colton
Dombeock LW Yt I
Ch/Rg
JMH
Knops Xg
Prior exposure necessary for antibodies IgG:
Transfusion
Pregnancy
Kell
Duffy
Kidd

3. White Cells and Platelets
Platelet specific antigens
Neutrophils specific antigens
Cytokines
HLA antigens

4. Pretransfusion Testing
ABO
Rh-D
Antibody screen (to look for antibodies to minor blood groups in the recipient‘s serum)
Infectious testing:
Bacterial testing of platelets
Hepatitis B virus
Hepatitis C virus
HIV 1,2
Chagas disease
Human T-Lymphotropic virus (HTLV-I/II)
Syphilis
West Nile virus
Zika

5. Pretransfusion Testing
ABO
Rh-D
Antibody screen (to look for antibodies to minor blood groups in the recipient‘s serum)
Infectious testing:
Bacterial testing of platelets
Hepatitis B virus
Hepatitis C virus
HIV 1,2
Chagas disease
Human T-Lymphotropic virus (HTLV-I/II)
Syphilis
West Nile virus
Zika

7. Blood Components
RRBCs: 42 days refrigerated: One unit raises hemoglobin by an average of 1 g/dL
Platelets: 5 days at room temperature (- one day for bacterial testing)
FFP: frozen for one year (by definition has 100% of clotting factors)
Cryoprecipitate: FFP thawed at cold temperature allowing large proteins to precipitate, 1 FFP: 1 Cryo unit
Typical dose 5-10 pooled units
Fibrinogen, von Willebrand factor, factor VIII, factor XIII
Primarily used for fibrinogen replacement: mg/dL increment per 10 units.

8. Blood Components Apheresis: centrifugation in a closed tubing system
All major blood products can be obtained by pheresis
Therapeutic pheresis:
Red cell exexchange
Plasmapheresis
Platelet pheresis
Leukapheresis
Stem cell collection
Blood
Plasma
Platelets
White cells
Red cells
Citrate anticoagulant

9. Transfusion Indications, RBCs
Red cell: Improve oxygen-carrying capacity
Hemoglobin of 7 g/dL threshold
Possible exception (higher threshold) for symptomatic cardiac patients
Restrictive transfusion associated with a trend toward lower hospital mortality, and reduced number of units transfused
Simple transfusion:
Partial correction of blood loss
One unit at a time is appropriate for most patients
Exchange transfusion
Reduce hemoglobin S concentration in sickle cell emergencies
Stroke prophylaxis in sickle cell disease

10. Transfusion Indications: Platelets
Platelet transfusion threshold:
10,000
20,000 fever, infection
50,000 surgery or active bleed
80-100,000 neurosurgery
Platelet dysfunction: No threshold
Massive transfusion: Generally more than one blood volume
Average increment per platelet dose: 25,000-50,000
Contraindications:
Absolute: TTP, HIT
Relative: ITP

11. Transfusion Indications: FFP
Temporary reversal of coagulopathy:
Liver disease, if bleeding or prior to invasive procedures
Duration of reversal few hours (shortest half-life of coagulation factor)
Timing before surgery
Dose: about 10 mL/kg (2-3 units in average adults)
Complete reversal not necessary (INR 1.5 or below)
Urgent warfarin reversal: 4 factor PCC preferred to FFP (Kcentra)
Factors II, VII, IX, X, protein S, protein C
Quick (15 min)
Low-volume
Expensive
TTP: Plasma exchange, replace deficient enzyme ADAMTS13

12. Transfusion Indications: Cryoprecipitate
Typical dose 5-10 pooled units ( mL volume)
Fibrinogen, von Willebrand factor, factor VIII, factor XIII
Primarily used for fibrinogen replacement: mg/dL increment per 10 units
Target fibrinogen > 100 mg/dL, >150 preferable
Uremic platelet dysfunction (vWF), DDAVP can be used

13. Massive Transfusion
One or more blood volume within 24 hours: ~ 10 units
Dilutional coagulopathy after units
Transfuse platelets, FFP, cryo
Citrate induced hypocalcemia
Perioral paresthesia, tetany
Treatment: Calcium gluconate, calcium chloride
Hypothermia
Blood warmer

14. Transfusion Complications: Acute hemolytic reaction
ABO mismatch
Recipient IgM Anti-A and/or Anti-B lyse donor cells
Intravascular hemolysis:
Complement activation
DIC
Red urine, hemoglobinuria
Renal failure
Fever, chills
Flank pain
Hypotension
Sense of impending doom
As little as mL of red cells sufficient to produce the reaction
Results from patient identification error
Difficult to recognize in anesthetized patients

15. Delayed Hemolytic Transfusion Reaction
Requires prior recipient sensitization to minor blood groups:
Pregnancy (fetal red cells in maternal circulation)
Transfusions (multiple)
Antibody level may fall below detection level with time
Initial antibody screen negative
Anamnestic response upon re-exposure
Extravascular hemolysis and drop in HGB 1-2 weeks following transfusion and new antibody on repeat screen
Typical scenario: multiparous woman transfused and improved, returns 10 days later with more severe anemia with no evidence of blood loss

16. Febrile Non-hemolytic Transfusion Reaction
About 1% of transfusions of cellular products
Fever, chills
Results from WBC cytokines released during storage
Reduced risk with leukoreduction
No evidence to support the use of antipyretics prior to transfusion
Diagnosis of exclusion, stop transfusion and rule out
Infection
Hemolysis
TRALI

17. Allergic Reactions Urticaria About 2% of transfusions
Antibodies or proteins in donor plasma
Itching, hives
Managed symptomatically
Antihistamines
Steroids
Resume transfusion

18. Anaphylactic Reactions
Uncommon
IgA deficient recipients
Respiratory distress
Wheezing
Hives
Shock
Prevention:
Transfuse from IgA deficient donors
Saline washed red cells

19. Transfusion Related Acute Lung Injury (TRALI)
HLA or neutrophil antibodies in donor serum to recipient white cells
More common in females donors (antibodies with pregnancy)
More common with plasma transfusion
Hypoxia, fever
Bilateral pulmonary infiltrates
Exclude other causes: Infections, heart failure
Supportive management
Exclude donor from future plasma donation

20. Alloimmune Platelet Refractoriness
HLA antibodies in the recipient bind to and rapidly clear transfused platelets
Poor platelet increment 10 minute to an hour post transfusion
Management:
HLA matched platelets
Cross-matched platelets
Prevention: Leukoreduction reduces the risk of developing HLA antibodies

21. Transfusion Associated GVHD
Donor T lymphocytes in:
Immunocompromised recipient
Donor related to recipient
Pancytopenia, rash, hepatitis, diarrhea, 1-4 weeks following transfusion
Diagnosis: Chimerism study to detect donor derived lymphocytes
Prognosis: Very high mortality
Prevention: Irradiated blood products

22. Post Transfusion Purpura
Recipient platelets lacking an antigen
Recipient has antibodies to that antigen
Antibodies destroy donor platelets in 1-2 weeks
Antibodies destroy own platelets (bystander effect)

23. Transfusion associated circulatory overload TACO
Common
Volume overload picture
Pulmonary edema
Elevated BNP
Supportive management

24. Infectious Complications
Most common with platelets: Stored at room temperature 1/2000
HBV 1/250,000
HIV 1/1,500,000
HCV 1/1,000,000
HTLV I-II 1/1,000,000
Minute risk
Babesiosis
Syphilis
West Nile
Chagas
Zika
CJD
Malaria
Lyme

25. Blood Product Modifications
Leukoreduction: Pre-storage filtration reduces the risk of
Febrile reactions
Alloimmune platelet refractoriness
CMV risk (equivalent to CMV negative blood)
Most blood products in the US are leukoreduced
Irradiation: Deactivates lymphocytes and reduces the risk of
Transfusion associated GVHD
Indications:
Immunocompromised host
Related donors

26. Saline Washing Repeated washing of red cells or platelets with saline
Removes plasma proteins
Transfusion in IgA deficient recipients
Recipients experiencing repeated severe allergic reactions

27. Question year-old female admitted with hematemesis and a hemoglobin of 6.5 g/dL, she received 3 units of packed red cells and at the time of discharge her hemoglobin was 9 g/dL. 10 days after discharge she was readmitted with fatigue, a hemoglobin of 6 g/dL. Total bilirubin of 2.5 mg/dL with direct bilirubin 0.5. Stool Hemoccult was negative. What is the most appropriate next step:
Transfuse 2 units of irradiated packed red cells
Repeat antibody screen
Upper endoscopy
Start steroids
Transfuse 2 units of O- blood

28. Answer 1 B
Delayed hemolytic transfusion reaction related to anamnestic response and re-appearance of minor blood group antibody in a multiparous woman. repeat antibody screen can detect the new antibody, and compatible units lacking the corresponding antigen can be transfused. Type O blood lacking the A and B major blood groups still has the minor groups. irradiation deactivates lymphocytes and does not affect the blood groups and will not be of benefit in this setting.

29. Question year-old healthy college student donating apheresis platelets for the first time. About an hour into the procedure, she is starting to feel a little anxious and restless, she is complaining of numbness around her mouth. Vitals are normal except for a heart rate of What is the most appropriate next step:
Stop the procedure
Give a dose of lorazepam for anxiety and continue the procedure
Tell her she should donate whole blood only from now on
Start calcium gluconate infusion
Draw blood cultures

30. Answer 2 D
Citrate which is used as anticoagulant in blood products and for apheresis procedures binds calcium and causes hypocalcemia, this presentation is typical for a citrate reaction. The treatment is calcium replacement most often given intravenously but oral replacement can be given.

31. Question year-old lady receiving chemotherapy, developed thrombocytopenia with a platelet count of units of random donor platelets were ordered and about 15 minutes into the infusion she developed fever of 102.2, chills, heart rate 110 and blood pressure 95/50. She has no wheezing, dyspnea or rash. In addition to stopping the transfusion, what is the most appropriate next step?
Give antihistamines, steroids, resume transfusion once she is feeling better
Test the donor for HLA antibodies
Draw blood cultures, start antibiotics, send the product to the blood bank for testing
Give intravenous furosemide
Give steroids, antihistamines, intravenous fluids, and transfuse washed blood products in the future

32. Answer 3 C
Platelets are stored at room temperature, and platelet transfusion is associated with the highest risk of bacterial contamination. Transfusion reactions associated with hemodynamic instability include bacterial contamination, anaphylactic reactions, circulatory overload, and TRALI, all of which except bacterial contamination are associated with prominent respiratory symptoms

33. Question year-old male receiving warfarin for deep vein thrombosis, hospitalized with lower gastrointestinal bleed and received 2 units of fresh frozen plasma for reversal of coagulopathy. 6 hours following the transfusion he developed dyspnea and hypoxia. Temperature Physical examination reveals no jugular vein distention or peripheral edema. CBC is normal. Which of the following is most likely to be associated with this condition?
Bilateral pulmonary infiltrates on chest x-ray
Reduced LEFT ventricular systolic function on echocardiogram
Female plasma donor
Antibodies against HLA antigens on recipient neutrophils
A, C, and D

34. Answer 4 E
Transfusion related acute lung injury, TRALI results from donor HLA antibodies or neutrophil specific antibodies in donor plasma reacting with recipient neutrophils, causing pulmonary infiltrates in the setting of normal cardiac function. Female donors are implicated more often because of prior allo-immunization from pregnancy

35. Question year-old male with alcoholic liver cirrhosis presents with pleural effusion requiring diagnostic thoracentesis. CBC shows a platelet count of 62,000, INR 1.4, PTT within the reference range. Prior to the procedure he should receive:
2 units of fresh frozen plasma to correct INR to 1.2 or below
1 platelet pack to correct the platelet count to 100,000
One unit of fresh frozen plasma and one platelet pack
10 units of cryoprecipitate
Proceed with the procedure without transfusion

36. Answer 5 E
There is no evidence that mild coagulopathy related to liver disease needs to be corrected prior to surgical interventions. platelet count greater than 50,000 is sufficient for most surgical interventions.

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