1. Transfusion Medicine: Types, Indications and Complications
David Harford
Hematology/Oncology

2. History of Transfusions
Blood transfused in humans since mid-1600’s
1828 – First successful transfusion
1900 – Landsteiner described ABO groups
1916 – First use of blood storage
1939 – Levine described the Rh factor

3. Transfusion Overview Integral part of medical treatment
Most often used in Hematology/Oncology, but other specialties as well (surgery, ICU, etc)
Objectives
Blood components
Indications for transfusion
Safe delivery
Complications

4. Blood Components Prepared from Whole blood collection or apheresis
Whole blood is separated by differential centrifugation
Red Blood Cells (RBC’s)
Platelets
Plasma
Cryoprecipitate
Others
Others include Plasma proteins—IVIg, Coagulation Factors, albumin, Anti-D, Growth Factors, Colloid volume expanders
Apheresis may also used to collect blood components

5. Differential Centrifugation First Centrifugation
Closed System
Whole Blood
Main Bag
Satellite Bag 1
Satellite Bag 2
First
Platelet-rich
Plasma
RBC’s

6. Differential Centrifugation Second Centrifugation
Platelet-rich
Plasma
RBC’s
Second
Platelet
Concentrate
Plasma
RBC’s

7. Whole Blood Storage Indications Considerations 4° for up to 35 days
Massive Blood Loss/Trauma/Exchange Transfusion
Considerations
Use filter as platelets and coagulation factors will not be active after 3-5 days
Donor and recipient must be ABO identical

8. RBC Concentrate Storage Indications Considerations
4° for up to 42 days, can be frozen
Indications
Many indications—ie anemia, hypoxia, etc.
Considerations
Recipient must not have antibodies to donor RBC’s (note: patients can develop antibodies over time)
Usual dose 10 cc/kg (will increase Hgb by 2.5 gm/dl)
Usually transfuse over 2-4 hours (slower for chronic anemia

9. Platelets Storage Indications Considerations Up to 5 days at 20-24°
Thrombocytopenia, Plt <15,000
Bleeding and Plt <50,000
Invasive procedure and Plt <50,000
Considerations
Contain Leukocytes and cytokines
1 unit/10 kg of body weight increases Plt count by 50,000
Donor and Recipient must be ABO identical

10. Plasma and FFP Contents—Coagulation Factors (1 unit/ml) Storage
FFP--12 months at –18 degrees or colder
Indications
Coagulation Factor deficiency, fibrinogen replacement, DIC, liver disease, exchange transfusion, massive transfusion
Considerations
Plasma should be recipient RBC ABO compatible
In children, should also be Rh compatible
Account for time to thaw
Usual dose is 20 cc/kg to raise coagulation factors approx 20%

11. Cryoprecipitate Description Storage Indication Considerations
Precipitate formed/collected when FFP is thawed at 4°
Storage
After collection, refrozen and stored up to 1 year at -18°
Indication
Fibrinogen deficiency or dysfibrinogenemia
vonWillebrands Disease
Factor VIII or XIII deficiency
DIC (not used alone)
Considerations
ABO compatible preferred (but not limiting)
Usual dose is 1 unit/5-10 kg of recipient body weight

12. Granulocyte Transfusions
Prepared at the time for immediate transfusion (no storage available)
Indications – severe neutropenia assoc with infection that has failed antibiotic therapy, and recovery of BM is expected
Donor is given G-CSF and steroids or Hetastarch
Complications
Severe allergic reactions
Can irradiate granulocytes for GVHD prevention

13. Leukocyte Reduction Filters
Used for prevention of transfusion reactions
Filter used with RBC’s, Platelets, FFP, Cryoprecipitate
Other plasma proteins (albumin, colloid expanders, factors, etc.) do not need filters—NEVER use filters with stem cell/bone marrow infusions
May reduce RBC’s by 5-10%
Does not prevent Graft Verses Host Disease (GVHD)

14. RBC Transfusions Preparations
Type
Typing of RBC’s for ABO and Rh are determined for both donor and recipient
Screen
Screen RBC’s for atypical antibodies
Approx 1-2% of patients have antibodies
Crossmatch
Donor cells and recipient serum are mixed and evaluated for agglutination

15. RBC Transfusions Administration
Dose
Usual dose of 10 cc/kg infused over 2-4 hours
Maximum dose cc/kg can be given to hemodynamically stable patient
Procedure
May need Premedication (Tylenol and/or Benadryl)
Filter use—routinely leukodepleted
Monitoring—VS q 15 minutes, clinical status
Do NOT mix with medications
Complications
Rapid infusion may result in Pulmonary edema
Transfusion Reaction

16. Platelet Transfusions Preparations
ABO antigens are present on platelets
ABO compatible platelets are ideal
This is not limiting if Platelets indicated and type specific not available
Rh antigens are not present on platelets
Note: a few RBC’s in Platelet unit may sensitize the Rh- patient

17. Platelet Transfusions Administration
Dose
May be given as single units or as apheresis units
Usual dose is approx 4 units/m2—in children using 1-2 apheresis units is ideal
1 apheresis unit contains 6-8 Plt units (packs) from a single donor
Procedure
Should be administered over minutes
Filter use
Premedicate if hx of Transfusion Reaction
Complications—Transfusion Reaction

18. Transfusion Complications
Acute Transfusion Reactions (ATR’s)
Chronic Transfusion Reactions
Transfusion related infections

19. Acute Transfusion Reactions
Hemolytic Reactions (AHTR)
Febrile Reactions (FNHTR)
Allergic Reactions
TRALI
Coagulopathy with Massive transfusions
Bacteremia

20. Frequency of Transfusion Reactions
Adverse Effect
Frequency
Comments
Acute Hemolytic Rxn
1 in 25,000
Red cells only
Anaphylactic hypotensive
1 in 150,000
Including IgA
Febrile Nonhemolytic
1 in 200
Common
Allergic
1 in 1,000
Delayed Hemolytic
1 in 2,500
RBC alloimmunization
1 in 100
WBC/Plt alloimmunization
1 in 10
WBC and Plt only

21. Acute Hemolytic Transfusion Reactions (AHTR)
Occurs when incompatible RBC’s are transfused into a recipient who has pre-formed antibodies (usually ABO or Rh)
Antibodies activate the complement system, causing intravascular hemolysis
Symptoms occur within minutes of starting the transfusion
This hemolytic reaction can occur with as little as 1-2 cc of RBC’s
Labeling error is most common problem
Can be fatal

22. Symptoms of AHTR High fever/chills Hypotension Back/abdominal pain
Oliguria
Dyspnea
Dark urine
Pallor

23. What to do? If an AHTR occurs
STOP TRANSFUSION
ABC’s
Maintain IV access and run IVF (NS or LR)
Monitor and maintain BP/pulse
Give diuretic
Obtain blood and urine for transfusion reaction workup
Send remaining blood back to Blood Bank

24. Blood Bank Work-up of AHTR
Check paperwork to assure no errors
Check plasma for hemoglobin
DAT
Repeat crossmatch
Repeat Blood group typing
Blood culture

25. Labs found with AHTR Hemoglobinemia Hemoglobinuria Positive DAT
Hyperbilirubinemia
Abnormal DIC panel

26. Monitoring in AHTR Monitor patient clinical status and vital signs
Monitor renal status (BUN, creatinine)
Monitor coagulation status (DIC panel– PT/PTT, fibrinogen, D-dimer/FDP, Plt, Antithrombin-III)
Monitor for signs of hemolysis (LDH, bili, haptoglobin)

27. Febrile Nonhemolytic Transfusion Reactions (FNHTR)
Definition--Rise in patient temperature >1°C (associated with transfusion without other fever precipitating factors)
Occurs with approx 1% of PRBC transfusions and approx 20% of Plt transfusions
FNHTR caused by alloantibodies directed against HLA antigens
Need to evaluate for AHTR and infection

28. What to do? If an FNHTR occurs
STOP TRANSFUSION
Use of Antipyretics—responds to Tylenol
Use of Corticosteroids for severe reactions
Use of Narcotics for shaking chills
Future considerations
May prevent reaction with leukocyte filter
Use single donor platelets
Use fresh platelets
Washed RBC’s or platelets

29. Washed Blood Products PRBC’s or platelets washed with saline
Removes all but traces of plasma (>98%)
Indicated to prevent recurrent or severe reactions
Washed RBC’s must be used within 24 hours
RBC dose may be decreased by 10-20% by washing
Does not prevent GVHD

30. Allergic Nonhemolytic Transfusion Reactions
Etiology
May be due to plasma proteins or blood preservative/anticoagulant
Best characterized with IgA given to an IgA deficient patients with anti-IgA antibodies
Presents with urticaria and wheezing
Treatment
Mild reactions—Can be continued after Benadryl
Severe reactions—Must STOP transfusion and may require steroids or epinephrine
Prevention—Premedication (Antihistamines)

31. TRALI Transfusion Related Acute Lung Injury
Clinical syndrome similar to ARDS
Occurs 1-6 hours after receiving plasma-containing blood products
Caused by WBC antibodies present in donor blood that result in pulmonary leukostasis
Treatment is supportive
High mortality

32. Massive Transfusions
Coagulopathy may occur after transfusion of massive amounts of blood (trauma/surgery)
Coagulopathy is caused by failure to replace plasma
See electrolyte abnormalities
Due to citrate binding of Calcium
Also due to breakdown of stored RBC’s

33. Bacterial Contamination
More common and more severe with platelet transfusion (platelets are stored at room temperature)
Organisms
Platelets—Gram (+) organisms, ie Staph/Strep
RBC’s—Yersinia, enterobacter
Risk increases as blood products age (use fresh products for immunocompromised)

34. Chronic Transfusion Reactions
Alloimmunization
Transfusion Associated Graft Verses Host Disease (GVHD)
Iron Overload
Transfusion Transmitted Infection

35. Alloimmunization Can occur with erythrocytes or platelets Erythrocytes
Antigen disparity of minor antigens (Kell, Duffy, Kidd)
Minor antigens D, K, E seen in Sickle patients
Platelets
Usually due to HLA antigens
May reduce alloimmunization by leukoreduction (since WBC’s present the HLA antigens)

36. Transfusion Associated GVHD
Mainly seen in infants, BMT patients, SCID
Etiology—Results from engraftment of donor lymphocytes of an immunocompetent donor into an immunocompromised host
Symptoms—Diarrhea, skin rash, pancytopenia
Usually fatal—no treatment
Prevention—Irradiation of donor cells

37. Transfusion Associated Infections
Hepatitis C
Hepatitis B
HIV
CMV
CMV can be diminished by leukoreduction, which is indicated for immunocompromised patients

38. Prevention X1 X ?2 Leukocyte Depletion Filter Gamma Irradiation
CMV Negative
Single Donor Platelets (Apheresis)
Febrile Transfusion Reactions X1 X
Alloimmunization
CMV ?2
Transfusion Related GVHD
1 In PRBC transfusion
2 Leukocyte Reduction by filtration may be an alternative to CMV-negative blood

39. Summary Blood Components
Indications
Considerations
Preparation and Administration of blood products
Acute and chronic transfusion reactions

40. Transfusion Reaction Summary
AHTR can be fatal
Stop the Transfusion
Monitor for symptoms and complete evaluation
FNHTR is a diagnosis of exclusion
TRALI (ARDS-like reaction)
Chronic Transfusion reactions
Prevention methods – using filters, irradiation and premedication