Transfusion Medicine

Question 1

What are packed RBCs?

Answer 1

the most common blood product used. Because they can be stored for a long time, their availability is usually excellent. Can store these (refrigerated) for up to 42 days

Used to increase oxygen carrying capacity

Question 2

How are packed RBCs prepared?

Answer 2

usually differential centrifugation

Spin them down, pull off the plasma and platelets

250 ml per unit; 1 unit will increase Hgb ~1g/dL

Question 3

From a practical patient management standpoint, knowing how much volume is infused when one unit is transfused is very important. Why?

Answer 3

Because some hypotensive patients will benefit from the added volume, and some (particularly those in congestive heart failure) will be placed at risk of fluid overload by it.

Question 4

Why is the max storage time 42 days?

Answer 4

The maximum storage time (42 days) was chosen because only up to 25% of the transfused red cells stored for that time period will lyse within 24 hours after transfusion.

Question 5

What are leukoreduced prbcs?

Answer 5

Most blood banks have been using primarily leukoreduced prbc’s for several years, but a few (chiefly in military hospitals and at the VA) only use them some of the time.

There is in fact little evidence that they make much difference clinically except in a handful of contexts (cardiothoracic surgery)

Question 6

Another blood product is plasma. What is it used for?

Answer 6

aka fresh frozen plasma (FFP). Used to replace clotting factors typically

Question 7

How is plasma prepared?

Answer 7

differential centrifugation

Spin down the red cells, pull off the plasma
200 - 250 ml per unit;

1 unit will increase clotting factors by ~20%

Can store it at -20C

Question 8

T or F. Plasma has to be ABO compatible

Answer 8

T (all the donor’s antibodies are present!)

Question 9

What is cryoprecipitate?

Answer 9

proteins that precipitate out of plasma at 4C

Question 10

What is cryoprecipitate used for?

Answer 10

to replace fibrinogen (rare), factor VIII, XIII (rare), and vMF

Question 11

How much cyroprecipitate should be given per unit?

Answer 11

15 ml per unit- will raise fibrinogen by 5-10 mg/dL

Question 12

T or F. Cryoprecipitate has to be ABO compatible

Answer 12

F. Can be stored at -20C

Question 13

T or F. Cryoprecipitate is the major form of treatment in both Hemophilia A and vMF deficiency

Answer 13

F. Both are usually treated via other means (hemophilia A= factor VIII concentrate)

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

Question 14

What are platelets (blood product) used for?

Answer 14

to stop bleeding when a patient has a low platelet count (thrombocytopenia)

or rarely to prevent bleeding when a patient has a low platelet count

Question 15

How are platelets prepared?

Answer 15

usually by plasmapheresis; less often via differential centrifugation

Spin down the red cells in a continuous flow centrifuge
Pull off the platelets, reinfuse red cells and plasma

300 ml per apheresis unit; 1 unit will increase platelet count by ~ 25K/ul (normal count is 150-450 K/ul)

Question 16

T or F. Platelets can be refrigerated and does have to be ABO compatible

Answer 16

F. Cannot refrigerate these and Does not have to be ABO compatible

However, Platelets DO express ABO antigens AND platelet preparations contain donor plasma.

Room temp storage life is only 4-5 days

Question 17

Most patients won’t start bleeding spontaneously until their platelet count is below _____.

Answer 17

10,000 (“10K”) per ul. That’s remarkably low, but the data is good.

So most platelet transfusions are ordered when a patient has a low count (below 50,000 per ul) AND is bleeding.

Question 18

How does the differential centrifugation process of platelets work?

Answer 18

The differential centrifugation process is less commonly used now, but if it is used it works like this: 1 “unit” of platelets is prepared per donor, and 5 units from different donors are pooled per transfusion order. 5 to 6 units of these “random donor” units contain approximately the same number of platelets as one apheresis unit.

Question 19

The most common reason to transfuse a patient is because ____.

Answer 19

they are severely anemic (meaning they can’t transport enough oxygen to stay alive).

We almost never transfuse whole blood in such cases. We use “packed red blood cells” (prbc’s), which we separate from plasma and platelets by differential centrifugation. So what you want to avoid is having the patient’s immune system attack and lyse the transfused cells.

Question 20

What is the structure of the “O” carbohydrate antigen?

Answer 20

GlcNac-Gal-GlcNac-Gal-Fucose (all hexametric sugars) linked to membrane via a membrane lipid or other proteins

Question 21

What is an “H” antigen?

Answer 21

Very rare individuals express only the 4-sugar precursor to O, called the H antigen.

Question 22

What enzyme is responsible for adding the sixth hexameric sugar to the O antigen to make an A or B antigen?

Answer 22

ABO glycosyltransferase

Question 23

“A” alleles add which sugar to the O antigen?

Answer 23

GalNac. Individuals with two “A” alleles or a single A and an O are termed “blood group A”

both via ABO glycosyltransferase

Question 24

“B” alleles add which sugar to the O antigen?

Answer 24

Gal. Individuals with two “B” alleles or a single B and an O are termed “blood group B”

both via ABO glycosyltransferase

Question 25

Antibodies against blood group antigens are of what type?

Answer 25

IgM- usually in high concentration These will lyse cells by fixing complement

Question 26

Understanding the immunology of the ABO antigens will allow you to transfuse a patient 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 antibodies to other antigens. So we need to know something about those antigens.

Answer 26

Understanding the immunology of the ABO antigens will allow you to transfuse a patient 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 antibodies to other antigens. So we need to know something about those antigens.

Question 27

The most antigenic protein on the red cell surface is what?

Answer 27

RhD (multiple alleles in the human gene pool) The most common and significant one is a complete deletion of the coding sequence

Question 28

Individuals with two deleted RhD alleles are called _____.

Answer 28

Rh negative. 15% of Europeanoid individuals are able to make antibodies to RhD, and those antibodies can have significant clinical implications

Question 29

What is RhCE?

Answer 29

a homolog of RhD gene that encodes two more antigenic proteins on RBCs- (C/c, E/e)

Question 30

What is RhoGAM?

Answer 30

anti-Rh-gamma globulin designed to bind and kill fetal RhD+ red cells before eternal cells can initiate an immune response and risk subsequent pregnancies via erythroblastosis fetalis

Question 31

Over 80% of D(-) individuals transfused with D(+) red cells develop antibodies. When is this 'acceptable"?

Answer 31

In males and older (non-childbearing age) women Women at or below childbearing age must never be allowed to develop anti-D antibodies, and that we need to know both the D-antigen status and the anti-D antibody status of all red cell donors and all patients for whom a transfusion is needed.

Question 32

T or F. D(+) red cells CAN be infused into other D(-) individuals.

Answer 32

T, We prefer not to, because they stand a good chance of developing anti-D antibodies later, but depending on what’s available in the blood bank in an emergency we can (and often do) make this type of choice

Question 33

Does plasma contain donor antibodies?

Answer 33

Yes, including those to ABO antigens. Thus, it MUST be ABO compatible

Question 34

What is a common complication of plasma transfusion?

Answer 34

If the recipient is lacking an entire class of plasma proteins, s/he can make antibodies to such proteins after a plasma transfusion Most common is IgA deficiency (1 in 300)- can cause anaphylacsis

Question 35

T or F. Platelets express ABO antigens

Answer 35

T.

Question 36

How long do platelets normally circulate for?

Answer 36

around 10 days. If ABO incompatible their survival will be shortened, but that is not felt to impair their utility for treating an acute bleeding episode.

Question 37

Do platlets preparations contain plasma?

Answer 37

Yes, about 1 unit per unit. It is considered acceptable in most cases to allow incompatible plasma to be infused during a platelet transfusion

Question 38

If your thrombocytopenic patient is bleeding heavily, you want to infuse them with whatever platelets are available, but (A) if they are ABO incompatible they will not last as long as compatible platelets, and (B) if they are ABO compatible but their plasma is NOT compatible, you could cause significant lysis of the patient’s red cells. (Example: Type O platelets transfused into a type A patient).

Answer 38

If your thrombocytopenic patient is bleeding heavily, you want to infuse them with whatever platelets are available, but (A) if they are ABO incompatible they will not last as long as compatible platelets, and (B) if they are ABO compatible but their plasma is NOT compatible, you could cause significant lysis of the patient’s red cells. (Example: Type O platelets transfused into a type A patient).

Question 39

When is it NOT considered acceptable to allow incompatible plasma to be infused during a platelet transfusion?

Answer 39

If the recipient has a very low blood volume (say, a neonate) the risk associated with the plasma is higher – and it is usually avoided, either with ABO identical platelets or by resuspending the platelets in a very low volume of plasma.

Question 40

Patients tend to become less responsive to platelet transfusion after 5-10 transfusions (i.e. their platelet counts stop going up much post transfusion). Severe cases require help from transfusion experts (typically the blood bank director).

Answer 40

Patients tend to become less responsive to platelet transfusion after 5-10 transfusions (i.e. their platelet counts stop going up much post transfusion). Severe cases require help from transfusion experts (typically the blood bank director).

Question 41

Review ABO red cell and plasma compatibility charts

Answer 41

Review ABO red cell and plasma compatibility charts

Question 42

What is a type and screen?

Answer 42

This is ordered if a transfusion is needed, OR in case one may be needed. Clinician provides a “current” blood specimen then typing for ABO and RH (D) antigens AND antibodies to each are examined Screening is for recipient antibodies to any minor red cell antigens

Question 43

What is a crossmatch?

Answer 43

This is ordered if a transfusion is needed or prior to those surgeries for which major blood loss is likely Performed by mixing donor red cells with patient plasma. Agglutination (seen under a microscope) indicates incompatibility. basically an indirect Coombs

Question 44

T or F. : If the antibody screen is negative, the crossmatch is compatible well over 99.9% of the time.

Answer 44

T. So when we’re dead sure that the screen is negative (i.e. we’ve done it at least twice on a given patient) we can skip the crossmatch. We call that an “electronic crossmatch.” In emergencies the blood bank CAN release type O(neg) blood for transfusion before the type, screen, and crossmatch is done. This “emergency release” places the patient at risk of a hemolytic reaction, but saving the 10-20 minutes required for typing and screening (and another 10 minutes for a crossmatch) can be a risk worth taking in time-urgent situations.

Question 45

What can happen if a patient that lacks a specific minor antigen in transfused with blood containing that antigen?

Answer 45

The patient can develop antibodies to that antigen so that any subsequent transfusion would require blood lacking the antigen to avoid an immune response

Question 46

How long does it take the blood bank to type the blood and screen the red cells?

Answer 46

about 20 minutes. if you think your patient might need a transfusion, get a blood specimen to the blood bank pronto so we can get our testing done. If you wait until the situation is critical, the time it takes to identify compatible units can be the difference between keeping your patient alive and not doing so.

Question 47

What is the main objective of a red cell transfusion?

Answer 47

to increase the patients oxygen carrying capacity

Question 48

What does hematocrit mean?

Answer 48

The Hematocrit is the fraction of the blood volume occupied by cells - Requires two measurements on the hematology analyzer - Usually but not always equal to 3 x Hgb

Question 49

Is the main criteria for transfusion lab values or the clinical status of the patient?

Answer 49

Clinical status. When the patient is symptomatic: - Increased HR, increased RR, confusion/weakness/dizziness Otherwise healthy patients can tolerate Hgb

Question 50

What are some things that red cell transfusions should NOT be used for?

Answer 50

1) old and frail patients who are healthy 2) Asymptomatic CAD. Transfusion of patients with CAD (i.e. those at risk for an MI) is often performed to get the Hgb above 10, athough there is little if any support for that in the literature – or, for that matter, for transfusing symptomatic CAD. 3) To expand blood volume (Hypotensive patients can be treated with expanded blood volume (i.e. isotonic IV fluids). Red cells should not be used for this purpose – the cost benefit ratio is unfavorable) 4) Promote wound healing

Question 51

What are some common things red cell tranfusions should be used for?

Answer 51

1) anemia- no magical hemoglobin level for transfusion

Question 52

What are some common things plasma tranfusions should be used for?

Answer 52

1) replace a missing plasma protein (factor VIII or IX, Antithrombin III, AdamTS13) 2) replace multiple missing plasma proteins

Question 53

What are some common things platelet tranfusions should be used for?

Answer 53

1) Treat an ongoing hemorrhage in a thrombocytopenic patient 2) Prevent spontaneous hemorrhage in patients with severe thrombocytopenia (minimally effective) 3) Treat or prevent hemorrhage in a patient with dysfunctional platelets 4) Prevent hemorrhage in patients undergoing invasive procedures

Question 54

What platelet levels would warrant a platelet transfusion in a thrombocytopenia patient with an ongoing hemorrhage?

Answer 54

Usual criterion is platelet count

Question 55

What could irreversibly modify platelets? I.e. when would a platelet transfusion be warranted due to dysfunctional platelets?

Answer 55

NSAIDS. if a patient has been on them within a few days of a current uncontrolled bleed, they may benefit from a platelet transfusion also if a patient has recently undergone cardiopulmonary bypass both low quality use

Question 56

When would invasive procedures warrant platelet transfusion?

Answer 56

There is some evidence that for one of the more common invasive procedures (placement of a central line) a threshold of 20 K/ul can be used for transfusion. But the AABB rates the evidence here as low quality.

Question 57

How common are adverse events in transfusions?

Answer 57

10% of all

Question 58

What are the main categories of adverse events in transfusions?

Answer 58

1) immune response 2) volume overload 3) graft vs. host disease 4) transfusion transmitted infection

Question 59

What are some possible immune responses from transfusions?

Answer 59

1) acute hemolytic reaction 2) antibody production to a minor red cell antigen 3) urticarial reaction to transfused plasma proteins 4) febrile reaction to transfused leukocytes

Question 60

How does acute hemolytic reaction present? From most to least common

Answer 60

- fever - chills - chest pain and hypotension - nausea, flushing, dyspnea

Question 61

What are the major possible clinical outcomes of acute hemolytic reactions?

Answer 61

renal failure and death Dumping a ton of hemoglobin out of transfused red cells and into the patient’s plasma can result in renal failure. At the most simple level, think of it as a huge amount of protein getting stuck in the filtration system.

Question 62

T or F. The more times you transfuse a patient, the greater the chance that the patient will develop an antibody to a minor red cell antigen

Answer 62

T. (“He’s got an antibody” is how the blood bank will give you the result.) Overall risk is ~4% per transfusion But some patients are at higher risk than others.

Question 63

What groups would be at higher risk of forming antibodies to a minor red cell antigen during a transfusion?

Answer 63

patients who have already formed one antibody poorly-defined "antibody formers" sickle cell patients: ~30% will form them

Question 64

Why do sickle cell patients commonly form antibodies after transfusions?

Answer 64

Antigen frequencies – genotypes, if you will - vary a great deal between ethnic groups. Most of the prbc’s in a blood bank are donated by non-African-Americans, and the antigenic differences are very likely to contribute to the higher risk of antibody formation in sickle cell patients That means that we should type sickle cell patients’ red cells, and type and crossmatch donor cells, not just for ABO and Rh antigens, but for a handful of the more common minor red cell antigens. That’s called an “extended phenotype” and an “extended crossmatch”, and it is on the threshold of becoming standard of care.

Question 65

Are red cells plasma free?

Answer 65

mostly, but not entirely

Question 66

What is the significance of red cells not being completely plasma free?

Answer 66

There is a great deal of antigenic 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 (urticaria) is the most common of these reactions, but a full blow anaphylactic reaction (i.e. airway swells, breathing is quickly compromised) can also occur (go back to the slide on immunology of plasma).

Question 67

Are febrile reactions to transfused leukocytes common? How are they treated?

Answer 67

These are common, affecting perhaps 1% of transfused patients, and usually treatable with tylenol. These reactions are much less frequent when leukoreduced prbc’s are used. remember that fever can also be part of an acute hemolytic reaction

Question 68

What is the most common adverse effect of blood transfusion?

Answer 68

Volume overload

Question 69

A normal patient’s blood volume is around 4.5 to 5 liters. Two units of red cells will increase their blood volume by about 10%. In a patient with heart disease, that can be a real problem – they will not be able to handle the extra cardiac workload, and fluid accumulation in organs like the lungs will compromise their function.

Answer 69

In most cases volume overload is easily treatable with the class of drugs called diuretics.

Question 70

Are transfusion transmitted infections common?

Answer 70

No, very rare Current risk of transmission of any of the above viruses per unit transfused is less than 1 in 100,000

Question 71

How are the risks of transfusion transmitted infections minimized?

Answer 71

Donor screening via: - Extensive questionnaire - Multiple criteria for deferral - -Travel to malaria-endemic areas - -IV drug use - -Confidential self-exclusion also serum tests for HIV, HCV, HBV, and others

Question 72

How can the risk of graft vs host be minimized?

Answer 72

Always use leukoreduced red cells for immunocompromised recipients Can reduce risk to zero via irradiation of the blood product When they occur, they can be severe, particularly in their effects on the GI tract (sloughing of epithelial cells).

Question 73

The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy- induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence)

Answer 73

The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy- induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence)

Question 74

Recommendation 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence)

Answer 74

Recommendation 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence)

Question 75

Recommendation 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence)

Answer 75

Recommendation 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence)

Question 76

Recommendation 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence)

Answer 76

Recommendation 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence)