Transfusion Medicine - Strom 03.18.15

Question 1

What are the 4 available blood transfusion products?

Answer 1

• Packed RBCs (prbcs; most common blood product you will need)
• Plasma
• Cryoprecipitate
• Plasma

Question 2

What are the use, preparation, and options associated with packed red blood cells (prbcs)?

Answer 2

• Use: increase O2 carrying capacity
• Preparation: usually differential centrifugation (spin down and pull out plasma and platelets
  1. 250 ml per unit; 1 unit will INC Hgb about 1 g/dL
  2. Can store refrigerated for up to 42 days
  3. Has to be ABO compatible
• Options: leukoreduced prbcs (most leukocytes removed) and irradiated prbcs (all leukocytes killed)

Question 3

Why is it that prbcs can be stored for 42 days?

Answer 3

• Only up to 25% of transfused RBCs stored for this time period will lyse within 24 hours after transfusion
• Excellent availability

Question 4

Why is it important to know that 1 unit of prbcs will increase Hgb about 1 g/dL?

Answer 4

• Very important from practical standpoint because some hypotensive patients will benefit from added volume, and some (particularly those in congestive heart failure) will be placed at risk of fluid overload by it

Question 5

What are the use and preparation of plasma transfusions?

Answer 5

• Use: usually to replace clotting factors
• Preparation: differential centrifugation (spin down red cells and pull off plasma)
  1. 200-250 ml per unit; 1 unit will INC clotting factors by about 20%
  2. Can store at -20 degrees
  3. Has to be ABO compatible (all donor Abs present)
• NOTE: aka, fresh frozen plasma (FFP) or frozen plasma

Question 6

What are the use and preparation of cyoprecipitate transfusions?

Answer 6

• Cryoprecipitate: proteins that precipitate out of plasma at 4 degrees
• Use: to replace fibrinogen, factor VIII, factor XIII, vWF
• Preparation: 15 mL per unit, and will raise fibrinogen levels by 5-10 mg/dL
  1. Can store at -20 degrees
  2. Does NOT have to be ABO compatible

Question 7

Why is deciding when a patient needs a plasma transfusion difficult?

Answer 7

• Because our assays for the functional status of blood clotting factors are not as sophisticated as we’d like them to be (we’ll cover this more later - coagulation week; apparently that’s a thing)

Question 8

Why is a cryoprecipitate transfusion unlikely (3), but also useful (1)?

Answer 8

• Can be used to treat genetic or acquired deficiencies of the factors that it contains, but:

A) factor VIII deficiency (hemophilia A) is usually treated with factor VIII concentrate

B) deficiencies of fibrinogen/factor XIII quite rare

C) vWF (von willebrand factor) deficiency is usually treated by other means

• BUT low volume of cryoprecipitate infusion improves its risk/benefit ratio relative to plasma in cases where plasma infusions can volume overload the patient

Question 9

What are the use and preparation of platelet transfusions?

Answer 9

• Use: to stop bleeding when a patient has a low platelet count
  1. Rare: to prevent bleeding when pt has very low platelet count
• Preparation: usually by plasmapharesis (spin down red cells in continuous flow centrifuge, pull off platelets, reinfuse red cells and plasma); less often via differential centrifugation
  1. 300 mL per apheresis unit; 1 unit will INC platelet count by about 25K/uL (normal 150-450 K/uL)
  2. No refrigeration; room temp storage life 4-5d
  3. Does NOT have to be ABO compatible

Question 10

At what platelet count will most patients start bleeding spontaneously? Why does this matter?

Answer 10

• Below 10,000 (“10K”) per ul -> remarkably low, but the data is good
• Most platelet transfusions are ordered when a patient has a low count AND is bleeding

Question 11

How does the differential centrifugation process work for platelets (if it is used)?

Answer 11

• Less commonly used now, but if it is used it works like this: 1 “unit” of platelets prepared per donor, and 5 units from different donors pooled per transfusion order.
• 5 to 6 units of “random donor” units contain approx same number of platelets as one apheresis unit

Question 12

Do platelets express ABO antigens?

Answer 12

• YES -> platelets DO express ABO antigens AND platelet preparations contain donor plasma
• However, these transfusions do NOT need to be ABO compatible

Question 13

What is the most common reason to transfuse a patient? What do we usually use in this case?

Answer 13

• Most common reason to transfuse a patient is because they are severely anemic (meaning they can’t transport enough oxygen to stay alive)
• Almost never transfuse whole blood in such cases, but use “packed red blood cells” (prbc’s), which are separated from plasma and platelets by differential centrifugation -> what you want to avoid is having pt’s immune system attack and lyse transfused cells

Question 14

What kind of antigens are on a red cell’s surface? Describe the O antigen.

Answer 14

• Targets on red cell surface that can induce an immune response include a # of membrane proteins and small set of complex carbohydrates
• Core structure of complex carbs is “O” antigen, which can be linked to mem lipid or any of several proteins, with essentially same antigenicity in those two locations
• Very rare individuals express only 4-sugar precursor to O -> H antigen
• Think of O-antigen as 5 linked hexameric sugars (don’t know exaclty what they’re for)

Question 15

What is the genetic and biochemical basis for ABO blood grouping?

Answer 15

• ABO glycosyltransferase enzyme adds sixth hexameric sugar to the O antigen
• Which sugar it adds depends on which allele(s) of the gene you inherited

Question 16

What are the three classes of alleles for the ABO blood grouping enzyme - what is the enzyme?

Answer 16

• Genome encodes ABO glycosyltransferase enzyme, which can attach a 6th sugar to the O antigen
• Multiple alleles of the gene for this enzyme in the human genome, but they fall into 3 categories:
  1. A alleles: encoded enzyme transfers GalNac sugar to O antigen
  2. B alleles: Gal (galactose) transferred
  3. O alleles: enzyme is inactive

Question 17

What are the alleles associated with A, B, AB, and O blood types?

Answer 17

• AB: one A and one B
• O: two Os
• A: one A and one O, or two As
• B: one B and one O, or two Bs

Question 18

How do ABO types determine red cell transfusion compatibility? Describe the pathologic process if there is a mismatch.

Answer 18

• Example: most type A peeps make Abs to B Ag
  1. IgM Abs
  2. Usually present in high concentration (high titer)
  3. These Abs usually fix complement, lysing RBCs
• If recipient is transfused with ABO-incompatible RBCs:
  1. They will lyse them all very quickly via acute hemolytic tranfusion reaction
  2. Can be fatal

Question 19

Why do people already have Abs to red cell Ags (i.e., no initial exposure to transfusion necessary to mount immune response)?

Answer 19

• Something in envo, probably polysaccharide antigens on surface of micro-organisms, almost always immunizes susceptible individuals to ABO antigens
• If their own red cells express A or B antigens, they don’t make antibodies to them (“self tolerance”)
• If their red cells don’t express one or the other of these antigens, they end up making the relevant antibodies

Question 20

What is antigenicity? Why is it relevant when conducting a red cell transfusion?

Answer 20

• A measure of how likely it is that a potential Ab binding site will actually induce an Ab response
• Many red cell surface Ags encoded by genes that show substantial allelic variation, and some of those alleles confer antigenicity on the protein
  1. For some Ags, the induced Abs are usually hemolytic, while they are not for others
  2. Some recipients appear to be more likely to devo Abs to RBC Ags than others
• Knowing ABO Ags will allow you to transfuse pt safely over 90% of the time, but that’s not an adequate margin of safety, AND we need to be able to transfuse patients who have Abs to other Ags

Question 21

What is the significance of RhD in transfusion medicine?

Answer 21

• Only PROTEIN Ag we routinely characterize in both donors and potential recipients
• > 80% D- transfused w/D+ devo Abs -> acceptable outcome in M and older F (esp. in emergency)
• D- women of childbearing age must never receive D+

Question 22

What are your concerns when transfusing plasma?

Answer 22

• Contains all donor Abs, incl those to ABO Ags
• If recipient lacking entire class of plasma proteins, can make Abs to those after plasma transfusion
• Most frequent problem of this sort is recipients that lack IgA (1 in 300 ppl) -> can have severe, life-threatening allergic rxn

Question 23

Describe the immunology of platelet transfusions, particularly ABO Ags, plasma contents, and repeat transfusions.

Answer 23

• Platelets express ABO Ags, but only circulate for 10 days, so ABO incompatibility not felt to impair their utility for acute bleeding episode (but they will not live as long) -> _ABO identical if you can, others if you must _
• PLT preps contain plasma; OK in most cases to allow incompatible infusion via PLT transfusion, except in recipient w/very low blood volume, i.e., neonate
• Pts tend to become less responsive to transfusions after 5-10 (i.e., PLT counts stop going up)

Question 24

Know this chart for plasma transfusions.

Answer 24

Good job!

Question 25

What is the role of “minor Ags” in transfusion?

Answer 25

• Include: RhCE, Duffy, Kell, Kidd -> blood bank has to assure pt doesn’t have Abs to these every time; more transfusions = more risk
• Can usually ID them and provide cells lacking that Ag
• Example: pt transfused and devo Ab to minor Ag, so blood bank uses pt serum to ID Ag and find blood that does not have it for transfusion -> can be easy or hard

Question 26

How does the blood bank provide compatible red cells?

Answer 26

• Clinician provides current blood specimen for type, screen -> ABO, RhD Ag typing, screening for recipient Abs to any know red cell Ags
• Crossmatch usually performed: mix donor RBCs w/pt plasma and look for agglutination
• If Ab screen (-), crossmatch compatible 99% of time
• In emergency, you can take a chance by transfusing O (-),” type compatible” units

Question 27

How might minor cell Ags be of practical concern during sx?

Answer 27

• Pt going to sx, and you want blood bank to have 2 units of prbc’s ready in case of unexpected blood loss
• Send specimen before sx so they can get the testing done ahead of time, esp in case Ab screen is (+) b/c this can take hours to resolve
• Can be done in 20 minutes in acute situation if Ab screen (-)
• Pts can die in scenarious like this

Question 28

What is the objective of red cell transfusion?

Answer 28

• To increase pt’s O2 carrying capacity
• Only exception is context of massive trauma, where objective is simpler: if pt has lost large fraction of blood volume, replace it (with every component of it, red cells, platelets, and plasma) fast
• Pt who has lost half his blood volume in the last five minutes will have a normal Hct, and will obviously need to be transfused anyway

Question 29

What are Hgb and Hct?

Answer 29

• Hgb: stuff in blood that carries O2 (single lab msmt)
• Hct: fraction of the blood volume occupied by cells
  1. Requires two measurements on hematology analyzer
  2. Usually, but not always equal to 3x Hgb

Question 30

What are the real indications for red cell transfusion?

Answer 30

• Guiding principle: most of the time lab #’s should not be used as indication for transfusion, but rather clinical status of the pt
• When pt is symptomatic: INC HR, RR, confusion, weakness, dizziness -> otherwise healthy pts can tolerate Hgb <7 (renal failure pts usually adapted to low Hgb)
• Acute blood loss and/or rapid volume expansion
• During or immediately after acute MI: increased mortality at Hgb <10
• Clear Hgb trend line that you can’t yet reverse

Question 31

What are the mythical indications for red cell transfusion?

Answer 31

• Pt is old and frail: aggressive transfusion provides no INC in survival for pts over 80 after hip replacement
• Asymptomatic coronary artery disease
• Expand blood volume (pt should be given isotonic fluids -> more cost efficient)
• Promote wound healing

Question 32

Details for acute blood loss and transfusion?

Answer 32

• O negative blood immediately available
• Type-specific blood will take 20 min longer
• Typed, screened, and crossmatched takes another 20 min

Question 33

Anemia and red cell transfusion details?

Answer 33

• Anemia is NOT a diagnosis
• Transfusion-dependent patients devo Abs -> Abs mean it will take longer to get cells ready, and they’ll devo more Abs
• No magic #’s: some pts func at Hgb 7, and some need transfusion at 9
• At most hospitals, you must provide rationale for transfusion if lab indication questionable (i.e., Hgb >7)

Question 34

Indications for plasma transfusion?

Answer 34

• Factor VIII, IX -> hemophilias A and B
• ATIII: rare, pro-thrombotic condition
• AdamTS13 deficiency: TTP
• Multiple: Coumadin toxicity with bleeding
• NOTE: with exception of TTP, plasma NOT the first choice therapy, but may be only option in some cases

Question 35

Indications for platelet transfusions?

Answer 35

• Treat ongoing hemorrhage in thrombocytopenic pt

1 Usual criterion PLT count <50k/uL

• Prevent hermorrhage w/severe thrombocytopenia:
  1. Fairly well-established criterion <10 K/uL
• Treat or prevent hemorrhage in pt with dysfunctional platelets
  1. Pts who have undergone cardiopulmonary bypass, or pts treated w/irreversible platelet-inhibiting drugs (i.e., Aspirin)

Question 36

What is the general risk % of adverse event with red cell transfusion? What are the 4 major categories of risk?

Answer 36

• 10%
• Immune response
• Volume overload
• Transfusion transmitted infection
• GVHD

Question 37

What might a poor immune response to transfusion look like?

Answer 37

• Acute hemolytic reaction: may kill your patient
• Production of Ab to minor red cell Ag
• Urticarial rxn to transfused plasma proteins
• Febrile rxn to transfused leukocytes

Question 38

How would an acute hemolytic rxn to transfusion present?

Answer 38

• Symptoms: fever 47.5%, chest pain 15%, hypotension, nausea, flushing, dyspnea, hemoglobinuria
• Be careful not to attribute these symptoms only to the patient being ill (transfusion pts tend to be ill)
• Dumping a ton of Hgb out of transfused red cells and into patient’s plasma can result in renal failure -> huge amount of protein getting stuck in the filtration system.

Question 39

What does it mean when people say a person has a rare blood type?

Answer 39

• Pt needs another transfusion, and when you send the blood bank a specimen for compatibility testing, they detect and identify new antibody, and obtain compatible red cells
• We may have to look around, in cases like this, for red cell units that lack one or more common antigens. Sometimes that takes an hour, sometimes it takes all day or longer.

Question 40

What is overall risk of production of Ab to a minor red cell Ag in a transfusion? High-risk groups?

Answer 40

• 4% per transfusion
• High-risk: 1) pts who have already formed one Ab, 2) poorly defined Ab formers, 3) sickle cell pts (about 30% form Ags) -> extended phenotype should be standard of care
  1. Standard compatibility: ABO, Rh; Sickle cell should be: ABO, Rh, RhCE, K(ell) compatible
  2. Ag freq, genotypes vary b/t ethnic groups. Most prbc’s in blood bank donated by non-AA, and Ag differences very likely to contribute to higher risk of Ab formation in sickle cell patients

Question 41

What is the most common reaction to plasma components in a red cell transfusion?

Answer 41

• Red cells mostly plasma free, but not entirely so
• Great deal of Ag diversity in plasma proteins, just as there is in red cell surface proteins, so patients can react to plasma components after a transfusion
• Severe itching (uriticaria) most common of these rxns, but a full blown anaphylactic rxn (i.e. airway swells, breathing is quickly compromised) can also occur

Question 42

If your patient develops a post-transfusion fever, what should you do?

Answer 42

• GO EXAMINE HER to make sure nothing else is going on (i.e., shortness of breath, acute abdominal or chest pain, hematuria)
• Could be febrile rxn to transfused leukocytes, which affects about 1% of transfused patients, and is usually treatable with tylenol
• BUT fever can also be a part of acute hemolytic rxn

Question 43

Why is volume overload a concern with transfusion?

Answer 43

• Normal pt’s blood volume around 4.5 to 5 liters
• Two units of red cells will increase blood volume by 10% -> in pt w/heart disease, can be a real problem – they will not be able to handle the extra cardiac workload

Question 44

What are the risks that often scare patients in regards to transfusions?

Answer 44

• Transfusion-transmitted infections
• Generally the lowest risks associated with transfusion -> less than 1 in 100,000

Question 45

How do we minimize risk of transfusion of viruses?

Answer 45

• Donor screening via:
  1. Extensive questionnaire
  2. Multiple criteria for deferral: 1) travel to malaria-endemic areas, 2) IV drug use, 3) confidential self-exclusion
• Serum tests for infectious agents (immunologic or PCR-based): HIV, HBV, HCV, several other, relatively rare agents

Question 46

What is GVHD, and how can you minimize risks?

Answer 46

• Immune response of transfused leukocytes against recipient tissues
• Rare unless recipient is immunocompromised
• Liver, GI, and skin
• Minimize risks:
  1. Always use leukoreduced red cells for immunocompromised recipients
  2. Can reduce risk to zero via irradiation of blood product