1. Introduction to Transfusion
Kathleen M. Madden MD
Jay S. Raval MD
Department of Pathology

2. Objectives Understand indications for transfusions
Describe the expected laboratory response patients should achieve with transfusion
Explain the indications for blood component modification
Highlight key facts of UNM’s Massive Transfusion Protocols

3. Who does not need a RBC transfusion?
A. 54 y/o F with ovarian cancer, no other medical problems, starting chemotherapy, Hgb 8.9 g/dL
B. 75 y/o M, history of myocardial infarction, admitted with pneumonia, Hgb 7.4 g/dL
C. 22 y/o F involved in a motor vehicle collision, hypotensive and tachycardic, Hgb 11.4 g/dL

4. Who does not need a RBC transfusion?
A. 54 y/o F with ovarian cancer, no other medical problems, starting chemotherapy, Hgb 8.9 g/dL
B. 75 y/o M, history of myocardial infarction, admitted with pneumonia, Hgb 7.4 g/dL
C. 22 y/o F involved in a motor vehicle collision, hypotensive and tachycardic, Hgb 11.4 g/dL

5. The main indication for RBC transfusion is tissue ischemia secondary to decreased O2 transport

6. Emergency RBC transfusion indications include:
Active hemorrhage
Hypovolemic shock
Laboratory evidence of ischemia
Lactic acidosis
Acute decrease in Hgb/Hct
Clinical evidence of decreased O2 transport
Dyspnea, tachypnea, tachycardia

7. Non-emergent RBC transfusion indications include:
Hgb <7g/dL (Hct <21%)
Hgb <8-10 g/dL (Hct <24-30%) in a patient with a known cardiac history
No symptomatic anemia (yet) at these transfusion thresholds

8. Considerations when transfusing RBCs
One RBC unit should increase the Hgb by 1g/dL and Hct by 3% in a 70 kg adult
Same as 4 mL/kg in a child
Single-unit transfusions should be ordered for non-bleeding patients
Additional units ordered after reassessing patient and rechecking post-transfusion Hgb/Hct
TRICC Trial: restrictive (hgb 8) vs liberal (hgb 10) transfusion strategy in ICU patients. Lower mortality, fewer cardiac events (especially MI and pulmonary edema), and lower multiorgan dysfunction in the restrictive group. Also decreased RBCs transfused by 54% and decreased RBC exposure by 33%
Transfuse one unit, reassess clinical situation

9. ASH/AABB Transfusion Recommendations
Don’t transfuse more units of blood than absolutely necessary
Don’t transfuse RBCs for iron deficiency without hemodynamic instability
Don’t perform serial blood counts on clinically stable patients
Don’t transfuse group O negative blood except to O negative patients and in emergencies to women of childbearing potential.
TRICC Trial: restrictive (hgb 8) vs liberal (hgb 10) transfusion strategy in ICU patients. Lower mortality, fewer cardiac events (especially MI and pulmonary edema), and lower multiorgan dysfunction in the restrictive group. Also decreased RBCs transfused by 54% and decreased RBC exposure by 33%
Transfuse one unit, reassess clinical situation

10. How long will it take you to get your RBC units?
Type and Screen must be up to date for type-specific RBCs
Type and Screen takes minutes if no antibodies are present
Electronic Crossmatch
Pt has >1 Type and Screen and no history of or current antibodies or ABO discrepancies
Very rapid
Antibodies present - additional time needed to identify antibody and provide antigen-negative or crossmatch compatible blood

11. Emergency Release RBCs
Can be provided if your patient is hemorrhaging and unstable and
There is no current type and screen
There is not time for the Blood Bank to provide antigen-negative or crossmatch compatible RBCs
O-negative RBCs: women and girls of child-bearing age
O-positive RBCs: all men and women who appear >50 years old
*Uncrossmatched blood must be approved by the Transfusion Medicine Service*

12. Plasma Pearls Source of all coagulation factors as well as fibrinogen
1 IU/mL of both pro- and anti-coagulant factors
Approximately 400mg fibrinogen
INR of plasma is variable but can be as high as 1.5

13. Indications for Plasma transfusion
Bleeding with decreased coagulation factors (INR > )
Prior to major surgical procedure with INR >
Therapeutic plasma exchange for selected conditions
Specific factor replacement when factor concentrates are unavailable

14. When is plasma not indicated?
Non-bleeding patient with elevated INR
Volume replacement
Protein source for nutritional support
If your bleeding patient has an elevated INR and you are unsure if they need plasma, you can order a ROTEM for whole blood evaluation of their ability to clot.

15. Why is plasma transfusion more effective at higher INR?
Plasma transfusion for increased INR based on thoughts: abn coag tests = decreased coag factors, plasma will correct this abnormality, correcting this abnormality decreases the risk of bleeding
Prolonged coag tests don’t necessarily mean coag factors have decreased low enough to affect clotting – need approx 30% of coag factors to form functional clot
Coag factor % doesn’t decrease below this minimal hemostatic threshold until INR is 1.7 – even then this doesn’t predict bleeding
Amount of decrease in INR/increase in coag factors will depend on the amount of plasma transfused and starting INR (v. low starting coag factor levels will have significant improvement in INR/PTT whereas the same amount of plasma transfused for higher starting coag factors will not affect INR/PTT as much)
Hall D., Walsh T.S. (2015) FFP Transfusion in Intensive Care Medicine. In: Juffermans N., Walsh T. (eds) Transfusion in the Intensive Care Unit. Springer, Cham

16. Plasma Transfusions Dose is 15-20 mL/kg NOT 2 units!
For a 70kg patient, this is 8 units plasma
ABO compatible with the recipient
Takes approximately 30 minutes to thaw plasma

17. Hepatic Failure Patients and Plasma Transfusion
Both pro- and anti-coagulant factors made by liver
Consequently liver failure resets the patient to have lower thresholds for bleeding and thrombosis
PT/aPTT do not predict which patients will bleed - plasma should not be empirically given to correct lab abnormalities without bleeding

18. von Willebrand factor + Factor 8
What is cryoprecipitate?
The big proteins:
Fibrinogen
Minimum Fgn: 150 mg
vWF (carries factor 8)
Minimum Factor 8: 80 IU
Factor 13
Fibronectin
The proteins “cryoprecipitate” (cold precipitate) out of solution
Cryoprecipitate formed by
Fibrinogen
von Willebrand factor + Factor 8
In practice, cryoprecipitate is used almost exclusively to replace fibrinogen (mostly in bleeding patients)

19. Indications for Cryoprecipitate Transfusion
Fibrinogen deficiency
Target fibrinogen >100 mg/dL for adequate hemostasis
Massive transfusion patients: >150 mg/dL
Postpartum hemorrhage: >200 mg/dL
Fgn <200 independently and significantly associated with worsening of bleeding in severe PPH
Each of the first two rounds of the OB MTP have a pool of cry

20. Cryoprecipitate Dosing
1 pool of cryoprecipitate = 5 units
1 pool is approximately 75 mL
Transfusing a 70kg patient 2 pools of cryoprecipitate should increase fibrinogen by 70 mg/dL
Pediatric dosing: can call Transfusion Medicine fellow/resident for help targeting a fibrinogen goal
Once thawed, the expiration is 6 hours
Takes us approximately 15 minutes to thaw cryo

21. Which patient needs a platelet transfusion?
A. 36 y/o M with a splenic laceration from a stab to the abdomen, platelet count 94 K
B. 10 y/o F with B-cell acute lymphoblastic leukemia between chemotherapy cycles, platelet count 31 K
C. 72 y/o F on Clopidogrel admitted with a subdural hematoma after a fall, platelet count 188 K
D. 54 y/o M with AML admitted for chemotherapy, no bleeding signs, platelet count 17 K

22. Which patient needs a platelet transfusion?
A. 36 y/o M with a splenic laceration from a stab to the abdomen, platelet count 94 K
B. 10 y/o F with B-cell acute lymphoblastic leukemia between chemotherapy cycles, platelet count 31 K
C. 72 y/o F on Clopidogrel admitted with a subdural hematoma after a fall, platelet count 188 K
D. 54 y/o M with AML admitted for chemotherapy, no bleeding signs, platelet count 17 K

23. Platelets: the Goldilocks of Blood Components
Platelet-rich plasma solution
Storage requirements:
Oxygen-permeable bag
Kept at room temperature
Gently agitated/rocked
Must “rest” for 12 hours before bacterial testing can be started
Highest-risk blood component for bacterial contamination and septic transfusion reactions

24. Indications for Platelet Transfusion: Quantitative Defects
Platelet Indications
Platelet Count
Prophylactic - Inpatient
<10 K
Prophylactic – Outpatient
<20 K
Prior to Invasive Procedure
<50 K
Active Bleeding
Intracranial/Central Nervous System Bleeding
<100 K
Intraocular Bleeding
< 100 K

25. Indications for Platelet Transfusion: Qualitative Defects
Platelet dysfunction
Antiplatelet medications
Congenital platelet functional defects
Following surgery using cardiopulmonary bypass

26. Platelet Dosing
For a 70kg adult, 1 unit of platelets should increase the platelet count by 25-50K
For pediatric patients, the dosing is mL/kg

27. How long will it take to get your platelets?
After collection and before expiration we have about a day window to transfuse platelets
On a good day, the Blood Bank has 7-9 platelet units for the hospital and cancer center
You may be asked to give half-units to your patients (should see a 15-25K increase in platelet count) when we have a shortage and are trying to get more platelets
You may be asked to hold on transfusing non- emergent patients until we can bring more platelets into the inventory

28. Blood Components & Indications
Plasma
Cryoprecipitate
RBCs
Platelets
Bleeding w/INR >1.5 – 2.0 (coagulopathic)
Massive hemorrhage
Therapeutic plasma exchange
Factor deficiency w/o concentrate
Low fibrinogen
<10K (inpt) - prophylactic
<20K (outpt) - prophylactic
<50K active bleed/major surgery
<100K CNS/eye injury/surgery
Massive hemorrhage
Aspirin/Plavix use with active bleed
When not to use plasma: INR >1.5-2 but not bleeding, for volume, as a protein source for nutrition
Decreased tissue oxygenation
Symptomatic anemia
Massive hemorrhage

29. Blood Product Modification
Leukoreduction
Washing
Irradiation

30. Leukoreduction
All cellular products (RBCs, platelets) are leukoreduced
Main reasons for leukoreduction:
Decrease incidence of febrile non- hemolytic transfusion reactions
Prevention of CMV transmission
Prevention of HLA alloimmunization
Considered equivalent to CMV seronegative products
HLA antibody formation requires donor lymphocytes to present HLA Class I antigens

31. Washed Blood Products
Removal of plasma proteins to decrease hypersensitivity to blood products
1-2 L of saline is used to remove ~99% of plasma
Indications may include:
IgA deficiency
History of severe allergic/anaphylactoid reactions to blood transfusions
IgA deficient patients: may develop anti-IgA and exposure to IgA leads to anaphylaxis. Either need intensely washed products or blood products from other IgA deficient donors
Removing unwanted antibodies: may be considered in patients who have repeated severe allergic or anaphylactic transfusion reactions despite premedication with Benadryl and Solu-Medrol

32. Issues with providing washed blood products
Washing changes expiration of blood products
Platelets = 4 hr
RBCs = 24 hr
Takes approximately 1 hour for washing process, then time for transportation to UNMH. Products must also be taken into Blood Bank inventory and then allocated
Quantitatively and qualitatively inferior unit secondary to washing process

33. How does irradiation work?
Used for cellular products
RBCs
Platelets
Granulocytes
Ionizing radiation damages the DNA of the irradiated cell but leaves normal cellular function intact
Indication for irradiation: prevent Transfusion- Associated Graft vs Host Disease (TA-GVHD)
Irradiated cells are unable to replicate but can still work. Plasma and Cryo DO NOT need to be irradiated.

34. What is TA-GVHD?
Graft-vs-host reaction that occurs after transfusion due to
Immunologically competent donor cells
Antigenic difference between graft and host detected by the donor cells
Inability of the host to reject the donor cells effectively
Affected organs include skin, GI tract, bone marrow, spleen, liver
Mortality >90%
Mortality is secondary to overwhelming sepsis from bone marrow failure
Only way to survive is to have a stem cell transplant ready

35. What are the common indications for irradiation?
Hematopoietic stem cell transplant recipients
Congenital Cellular Immune Deficiency
Intrauterine/neonatal transfusions
Infants up to 6 months old
All pediatric malignancies
Hematologic malignancies
Transfusion from family members or HLA-matched products
Treatment with purine analogs, anti-thymocyte globulin, or Alemtuzumab
Cong Cellular Deficiency: can be suspected or confirmed (why we irradiate neonates to 6 mo) - includes SCID, DiGeorge, Ataxia Telangiectasia, Wiskott-Aldrich

36. When is irradiation NOT indicated?
Solid organ transplantation
Adult solid organ tumors
Autoimmune diseases
HIV/AIDS
Caveat: if patient is severely lymphopenic (ALC < 500) or treated with medications for which irradiation is indicated, cellular blood products will be irradiated

37. Changing gears to massive transfusions

38. What is a massive transfusion?
Acute administration of >1/2 estimated blood volume in 3 hours
Replacement of 10% of the total blood volume/minute
Anticipated replacement of total blood volume in 24 hours
Pediatric patients: transfusion of >40 mL/kg RBCs
Definitions are retrospective based on amount of bleeding or blood products replaced over a period of time

39. When should you consider activating the MTP?
If you think any of the above circumstances apply to your patient OR
If your patient is bleeding and you are concerned that it is already uncontrolled or it may become uncontrolled, activate the MTP!

40. How will activation of the Massive Transfusion Protocol help your patients?
Protocol is designed to mimic whole blood resuscitation
Each round of the MTP contains RBCs, Plasma, and Platelets
Having the MTP Protocol set up in advance streamlines the allocation and rapid delivery of blood products to patients
MTP is designed so that once activated, you do not need to continuously reorder blood products

41. Important points to remember when ordering a MTP for your patient
You must choose the appropriate MTP in powerchart
Pediatric Massive Transfusion
Trauma/Surgical Massive Transfusion
Obstetric Massive Transfusion
You MUST initiate and sign the powerplan
You MUST call the Blood Bank to notify them that you activated a MTP

42. Information to provide to the Blood Bank
Patient’s name and MRN
Patient’s location
Attending physician responsible for the patient
Point of contact name and phone number
For pediatric patients: estimated/known weight in kg

43. Adult and OB MTP Rounds
Cryoprecipitate is not provided nor built into the ADULT MTP rounds.
One pool of cryoprecipitate is provided with each of the first two OB MTP rounds

44. Pediatric MTP rounds are weight-based
Cryoprecipitate is not provided nor built into the MTP rounds – it must be ordered separately
Blood product dosing for pediatric patients: 15mL/kg

45. The most important initial labs are included in the MTP powerplans
Type and screen
Emergency Hemorrhage Panel (EHP)
Tests included: Hemoglobin, Platelet Count, PT/INR, Fibrinogen
Results in 15 minutes upon specimen arrival to the lab
Hand deliver a lavender top and a light blue top tube to the lab
New EHP should be sent after every round or every minutes
Important to know patient’s type before we start giving o pos/neg if no type is in system

46. Picking up MTP rounds
The clinical service is responsible for picking up all blood products required during the MTP
RBCs and other blood products are generally available for pickup at the Blood Bank unless otherwise arranged
The Blood Bank will notify the Point of Contact when each new round is ready to be picked up
A new round will automatically be prepared once previous round is picked up
RBCs/plasma can be set to be picked up in the fridge between TSI and the MICU if necessary

47. Endpoints of Massive Transfusion
Physician declares hemostasis based on the absence of bleeding
The treating physicians agree the patient is adequately resuscitated based on normalizing vital signs
Further resuscitation is deemed to be futile
The point of contact must notify the Blood Bank when the MTP has ended

48. Remember: If your patient is bleeding and you’re concerned it is already uncontrolled or may become uncontrolled, activate the MTP

49. Questions?