FINAL LECTURE L1: ADVERSE EFFECTS OF BLOOD TRANSFUSION

Question 1

An unintended and deleterious occurrence associated with blood component transfusion, that may occur before, during, or after a transfusion.

Answer 1

adverse event

Question 2

T/F: Adverse events include “incidents” and “adverse reactions”.

Answer 2

T

Question 3

Identify if INCIDENT or ADVERSE REACTION:

A harmful effect observed in a transfusion recipient that is temporally associated with a blood component transfusion.

Answer 3

ADVERSE REACTION

Question 4

Identify if INCIDENT or ADVERSE REACTION:

Any error that could affect the quality or effectiveness of a blood product or could have led to an adverse reaction to a transfusion recipient.

Answer 4

INCIDENT

Question 5

In the United States, fatalities associated with transfusion or blood donation are required to be reported to what US administration?

Answer 5

Food and Drug Administration (FDA)

Question 6

The FDA annually issues a summary of fatalities following transfusion and blood collection through this mandatory reporting system. Who investigates all of the reported cases?

Answer 6

A team of medical officers from the FDA Center for Biologics Evaluation and Research (CBER)

Question 7

The recognition and evaluation of suspected transfusion
reactions involve what two critical components?

Answer 7

(1) The clinical recognition by the person administering the transfusion, that a suspected transfusion reaction may be occurring or has occurred

(2) The laboratory investigation of a transfusion reaction.

Question 8

If the infusion is still in process, what is the first step once a transfusion reaction is suspected?

Answer 8

immediately stop the transfusion

Question 9

Once a transfusion reaction is suspected and the transfusion was immediately stopped, what is the next step?

Answer 9

Follow a standard procedure to send appropriate specimens to the laboratory for a transfusion reaction investigation.

Question 10

Final assessment of the transfusion reaction is the responsibility of which personnel?

Answer 10

medical director or an appropriate designee

Question 11

This is the collection of information on the complications of transfusion, analysis of these data, and subsequent data-driven improvements in transfusion practices.

Answer 11

Hemovigilance

Question 12

Signs and symptoms of transfusion reactions

Answer 12

• Fever (≥39°C or ≥2°C rise)
• Hematuria
• Bronchospasm
• Hypoxemia (O2sat. <90%)
• Hemoglobinuria
• Pulmonary edema
• Tachycardia (>120/min or >40/min rise)
• Nausea or vomiting
• Chills/rigors
  -Tachypnea (>28/min)
• Urticaria (hives)
• Pain—abdominal, back, chest, infusion site, headache
• Hypertension (rise in systolic BP >30 mm Hg)
• Pruritis
• Oliguria or anuria
• Hypotension (drop in systolic BP >30 mm Hg)
• Rash
• Disseminated Intravascular Coagulation (DIC)

Question 13

This is the development of non-ABO antibodies following RBC transfusion, pregnancy, or transplantation.

Answer 13

Alloimmunization

Question 14

The immunological response to RBC protein antigens is not very robust, except for what antigen?

Answer 14

D antigen

Question 15

About how many percent of healthy D-negative persons exposed to the D antigen will
develop anti-D?

Answer 15

about 85%

Question 16

It has been long recognized that some individuals may be more susceptible than others to developing RBC alloantibodies. The people who represent the
majority of patients identified with alloantibodies are called?

Answer 16

responders

Question 17

Within patients who have been alloimmunized, studies show about a quarter of these have or develop more than one alloantibody. This subgroup has been called what?

Answer 17

hyperresponders

Question 18

Biological factors associated with responders may include what?

Answer 18

• genetics
• inflammatory state of the patient
• sex
• age

Question 19

They appear to be poor responders

Answer 19

• Neonates
• Young children
• Elderly

Question 20

T/F: The rate of alloimmunization in patients with sickle cell disease (SCD) is much lower than the general population

Answer 20

F (rate is much HIGHER)

Question 21

HTRs are classified as

Answer 21

acute or delayed

Question 22

This is the accelerated destruction of transfused RBCs due to antibody-mediated incompatibility.

Answer 22

Acute Hemolytic Transfusion Reaction (AHTR)

Question 23

It is defined as the combination of signs and symptoms associated with hemolysis, biochemical evidence of hemolysis, and serologic evidence of RBC incompatibility occurring during or within 24 hours after transfusion.

Answer 23

Acute Hemolytic Transfusion Reaction (AHTR)

Question 24

The vast majority of AHTRs is due to what transfusion?

Answer 24

RBC transfusion

Question 25

In general, the severity of an AHTR is related to the amount of?

Answer 25

incompatible blood transfused

Question 26

The most common symptom in AHTR

Answer 26

fever

Question 27

Fever in AHTR often occurs with

Answer 27

chills or rigors

Question 28

Pain is another frequent symptom in AHTR that can be localized to which body parts?

Answer 28

flanks, lower back, abdomen, or infusion site

Question 29

This symptom occurs in about 10% of AHTRs

Answer 29

hypotension

Question 30

This symptom is usually detected biochemically by elevated blood urea nitrogen (BUN) and creatinine.

Answer 30

Acute Kidney Injury (AKI)

Question 31

AKI can be severe enough to cause what symptom?

Answer 31

decreased or absent urine output

Question 32

Main causes of renal dysfunction after hemolysis

Answer 32

shock, and disseminated intravascular coagulation (DIC)

Question 33

first steps in treating AHTRs

Answer 33

Early and aggressive fluid resuscitation and blood pressure management

Question 34

Essential tests for diagnosis between DIC and other coagulation abnormalities

Answer 34

- Activated partial thromboplastin time (aPTT) - Prothrombin time (PT) - Thrombin time - D-dimer - Fibrinogen - Platelet count

Question 35

T/F: Platelets are typically selected for transfusion based on shelf life and availability rather than major or minor ABO compatibility.

Answer 35

T (that's why HTRs can occur in patients receiving ABO mismatched platelet transfusions)

Question 36

Major ABO incompatibility may result in decreased platelet increments after transfusion and explain occasional cases of what phenomenon related to platelets?

Answer 36

phenomenon of platelet refractoriness

Question 37

Minor ABO incompatibility may cause HTRs due to transfusion of what antibodies in the donor plasma?

Answer 37

anti-A or, rarely, anti-B in the donor plasma

Question 38

The donors and recipients of platelet units implicated in HTRs are almost always what blood groups?

Answer 38

donor: group O recipient: group A

Question 39

Antibody titer did not appear to predict HTRs after minor ABO-incompatible platelet transfusion, which suggests that other mechanisms are involved such as?

Answer 39

- antibody subtype - individual characteristics of the transfusion recipient

Question 40

RBC alloantibodies mediate RBC destruction through?

Answer 40

- Activating the complement (C′) cascade - Through the Fc receptor (FcR)-mediated phagocytosis by macrophages, primarily in the spleen.

Question 41

T/F: 4 different IgG subclasses have the same level of affinity for binding antigens and FcRs, and also the same efficiency for activating C′

Answer 41

F (different affinity and efficiency)

Question 42

How many different FcRs are there, each with distinct affinities for various IgG subclasses and either activating or inhibitory effects?

Answer 42

6

Question 43

While a mixture of different IgG subclasses is usually found in the antisera of patients with alloantibodies, how many subclasses are typically predominant?

Answer 43

one or two

Question 44

Haptoglobin-hemoglobin complexes are bound to what receptor on monocytes and macrophages?

Answer 44

CD163

Question 45

The binding of haptoglobin-hemoglobin complexes to CD136 on monocytes and macrophages initiates what?

Answer 45

initiates receptor-mediated uptake and intracellular degradation of hemoglobin

Question 46

T/F: Circulating supply of haptoglobin is quickly depleted in even mild hemolysis.

Answer 46

T

Question 47

Free hemoglobin is observed visibly as what color of plasma?

Answer 47

pink to red plasma (hemoglobinemia)

Question 48

Free hemoglobin is observed visibly as what color of urine?

Answer 48

brown to red discoloration of the urine (hemoglobinuria)

Question 49

The inflammatory response to hemolysis that drives the clinical features of an HTR

Answer 49

activation of the FcR pathway

Question 50

A positive DAT 24 hours to 28 days after transfusion with either a positive eluate or a newly identified alloantibody in the plasma or serum and evidence of hemolysis.

Answer 50

Delayed Hemolytic Transfusion Reaction (DHTR)

Question 51

Evidence of hemolysis in DHTR

Answer 51

- Inadequate rise in hemoglobin after transfusion - A rapid drop in hemoglobin to the pretransfusion level - Spherocytes on peripheral blood smear - Biochemical evidence of hemolysis

Question 52

Defined as the same serologic findings as DHTR but without evidence of hemolysis

Answer 52

Delayed serologic transfusion reaction (DSTR)

Question 53

Most cases of DHTR appear between how many days post-transfusion?

Answer 53

7–10 days

Question 54

In some cases of DHTR, especially in transfused postsurgical patients, they will be unsuspected because?

Answer 54

postoperative anemia is attributed to other causes

Question 55

DHTR and DSTR are a particular problem in which patients?

Answer 55

sickle cell disease (SCD) patients who are chronically transfused

Question 56

The most frequent sign of DHTR in SCD patients with alloimmunization is

Answer 56

hemoglobinuria

Question 57

In SCD patients with DHTR, hemoglobinuria is usually associated with?

Answer 57

painful crises and often acute chest syndrome

Question 58

Mortality percentage (in range) of SCD patients with DHTR

Answer 58

5-10%

Question 59

Patients with SCD can also rarely develop what syndrome following transfusion?

Answer 59

hyperhemolysis syndrome

Question 60

Hyperhemolysis syndrome has been reported in what other conditions?

Answer 60

thalassemia, myelofibrosis, and lymphoma

Question 61

Hyperhemolysis syndrome typically develops within how many days after transfusion?

Answer 61

7-10 days

Question 62

Hyperhemolysis syndrome is manifested by signs and symptoms of

Answer 62

- Intravascular hemolysis - Painful vaso-occlusive crises - Severe anemia - Hemoglobin level below the pretransfusion level

Question 63

Hemolysis of both patient and transfused RBCs can be inferred from what test?

Answer 63

hemoglobin electrophoresis

Question 64

The pathogenesis of hyperhemolysis syndrome is not well understood but several mechanisms are likely involved, including

Answer 64

- Bystander hemolysis from C′activation - Increased macrophage destruction of RBCs - Increased programmed cell death of RBCs

Question 65

What do you call the programmed cell death of RBC?

Answer 65

eryptosis

Question 66

The pathogenesis of hyperhemolysis syndrome likely involves eryptosis due to?

Answer 66

due to increased circulating proinflammatory mediators