10/9 Transfusion Med - Blood Product Management

Question 1

What are the transfusion risks from RBCs?

Answer 1

• transfusion reactions
• immunomodulation (increased risk of infection)
• RBC storage lesion (decreased 2,3DPG, NO production in vitro, increased mortality, infections?)
• Increased mortality and cardio-pulmonary complications

Question 2

What are the transfusion risks from plasma/platelets?

Answer 2

• Transfusion reactions - TRALI (transfusion-related acute lung injury), TACO (transfusion associated circulatory overload), allergic/anaphylactic, septic (platelets)
• HLA sensitization (platelets-transplant)
• TBD

Question 3

The risk of death with transfusions is low but not zero, but what risk is much higher with transfusions?
What does this mean about when transfusions should be performed?

Answer 3

The risk of increased morbidity is much higher.

Transfusion should only be performed when benefits are proven

Question 4

What are the parameters for ideal transfusion practices of RBCs?

Answer 4

1-identify clinical situations where patients may benefit from RBC transfusions
2-identify studies that demonstrate that transfusions significantly improve outcomes
3-demonstrate that the benefits of transfusions outweigh the risks and do so in a cost-effective manner

Question 5

What study had the following setup?
838 critically ill patients with hemoglobin concentration of less than 9.0g/dL were randomly assigned to either a restrictive transfusion strategy (RBCs transfused if hemoglobin concentration dropped below 7.0g/dL) or a liberal strategy (RBCs transfused if hemoglobin concentration dropped below 10.0g/dL)

Answer 5

TRICC (transfusion requirements in critical care) Trial

Question 6

What were the results of the TRICC Trial?

Answer 6

A restrictive strategy of RBC transfusion is at least as effective and possibly superior to a liberal transfusion strategy in critically ill patients
Liberal strategy patients shown to have decreased survival

Question 7

What is the importance of the TRICC Trial for transfusion medicine?

Answer 7

It is a landmark study that led to rethinking about risk/benefit analysis of blood transfusions

Question 8

What study had the following setup?
Randomized unblended study with 2016 patients enrolled (50 year-olds after hip surgery with hemoglobin concentration less than 10h/dL and cardiovascular disease)
Liberal and restrictive transfusion strategies were compared

Answer 8

FOCUS

Question 9

What were the results of FOCUS?

Answer 9

No benefit of a liberal transfusion approach
The restrictive strategy group received much less blood
Giving more blood did not improve outcomes (death/ability to walk) even in this “high-risk” population

Question 10

What study had the following setup?
Prospective randomized control trial with 502 patients (adults undergoing cardiac surgery with hemoglobin less than 10g/dL)
Liberal and restrictive transfusion strategies were compared

Answer 10

TRACS (transfusion requirements after cardiac surgery)

Question 11

What were the results of TRACS?

Answer 11

Restrictive strategy group received less blood (47% of patients) compared with liberal group (78%)
Restrictive perioperative transfusion strategy compared with more liberal strategy resulted in non-inferior rates of outcomes of 30-day mortality and morbidity
Liberal strategy no worse than restrictive strategy but also not significantly better

Question 12

What study had the following setup?
Prospective randomized trial with 921 patients (adults with severe GI bleed)
Divided into two groups: Hg <9

Answer 12

Transfusion strategies for acute upper GI bleeding

Question 13

What were the results of Transfusion strategies for acute upper GI bleeding?

Answer 13

Restrictive strategy group significantly imrpoved outcomes (LESS is MORE in this patient group)
Restrictive strategy group received less blood compared to liberal group

Question 14

What do multiple large randomized studies indicate about RBC transfusions and survival and mortality?

Answer 14

RBC transfusions do not improve survival and liberal transfusion strategies may actually increase mortality in some settings

Question 15

What are the AABB RBC guidelines (4 recommendations)?

Answer 15

1 - adhere to a restrictive transfusion strategy (7-8 g/dL) in hospitalized stable patients (strong evidence)
2 - adhere to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and consider transfusions for patients with symptoms or hemoglobin levels of 8g/dL or less (moderate-quality evidence)
3 - cannot recommend for or against liberal or restrictive transfusion threshold for hospitalized hemodynamically stable patients with acute coronary syndrome (low-quality evidence)
4 - suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (low-quality evidence)

Question 16

What patient population may benefit from a more liberal transfusion practice? (not yet fully proven)

Answer 16

Patients with acute coronary syndrome (any condition brought on by sudden, reduced blood flow to the heart)

Question 17

What was one of the first studies demonstrating the immunosuppressive effect of RBC transfusions?
Why is this strategy not used?

Answer 17

Beneficial effect of operation-day blood-transfusions on human renal-allograft survival (1978)
The study was done in the pre-cyclosporine era; cyclosporine was approved in 1983 and greatly improved graft survival

Question 18

What type of RBCs were found to be more immunosuppressive?
Leukoreduced RBCs
Non-leukoreduced RBCs

Answer 18

non-leukoreduced RBCs

Question 19

What was a study done at UIowa that confirmed that in renal transplantation RBC transfusions appear to be immunosuppressive?

Answer 19

Transfusion and renal allograft survival

Question 20

T/F

RBC transfusions increase the risk of infection

Answer 20

there is an association between blood transfusion and infection risk but unclear if confounding factors could account for this increased risk

Question 21

What were the conclusions of:

Healthcare-associated infection after RBC transfusion; a systematic review and meta-analysis

Answer 21

Compared liberal vs restrictive strategies
Among hospitalized patients a restrictive RBC transfusion strategy was associated with a reduced risk of health care associated infection

Question 22

What is the number needed to treat with restrictive transfusion strategy to avoid infection?

Answer 22

38

Question 23

In a comprehensive analysis of randomized studies, what was the difference in infection rate between the restrictive groups and the liberal groups?

Answer 23

5%
Restrictive groups 11.8%
Liberal groups 16.9%

Question 24

What is the RBC storage lesion?

Answer 24

degradation of RBCs during storage at 4C in the blood bank for up to 42 days

Question 25

What is the estimate of percentage of transfusions that are done without a good indication?

Answer 25

40-60%

Question 26

T/F
Allogenic blood transfusion improves outcomes in only 5% of clinical scenarios for patients without trauma or active hemorrhage

Answer 26

False 11%

Question 27

What were the results of a retrospective 2008 study (Duration of red-cell storage and complications after cardiac surgery)?

Answer 27

In patients undergoing cardiac surgery, transfusion of RBCs that had been stored for more than 2 weeks was associated with a significantly increased risk of postoperative complications

Question 28

What did scanning electron micrograph (SEM) studies show about stored RBCs?

Answer 28

People think they are transfusing characteristic RBCs but actually the cells look like burr cells (more fragile & less deformable)

Question 29

What are the parameters for ideal transfusion practices of prophylactic FFP/platelets?

Answer 29

1 - identify clinical situations where patients are at high risk of bleeding
2 - identify studies that demonstrate that transfusion interventions significantly reduce the risk of bleeding
3 - demonstrate that the benefits of transfusions outweigh the risks and do no in a cost-effective manner

Question 30

T/F
If FFP and platelets were drug products they would be approved for very few indications outside of the actively bleeding patient

Answer 30

True

Question 31

Many studies of platelet transfusion triggers in high risk patients that all show that lower trigger had equivalent outcomes with few transfusions
What were the results of the 1st study to see if eliminating prophylactic platelet transfusions was safe?

Answer 31

Therapeutic vs prophylactic platelet transfusions
concluded that therapeutic strategy could become a new standard of care after autologous stem-cell transplantation
however, prophylactic platelet transfusion should remain the standard for patients with AML (therapeutic strategy too risky)

Question 32

For review results of additional platelet studies

Answer 32

• Risks associated with central catheter placement in liver disease were quite low (Central venous catheterization in liver disease)
• Elevated INR did not predict high risk of bleeding (US-guided thoracocentesis)
• There was no correlation between PT and the time it took the liver to stop bleeding after a biopsy & similar results with platelet counts (Bleeding during liver biopsy)

Question 33

T/F

Plasma is not clearly indicated in a non-bleeding patient

Answer 33

True

Question 34

What are the 4 indications for plasma transfusion

Answer 34

1 - bleeding patient with inherited or acquired coagulopathy due to factor deficiency and specific factor replacement is not available
2 - bleeding patient who requires replacement of multiple coagulation factors (DIC, liver failure)
3 - bleeding patient needing massive transfusion protocol
4 - bleeding patient on warfarin for whom reversal with vitamin K will be too slow

Question 35

What are the main points of plasma use?
INR useful?
When does bleeding occur?
FFP complications?

Answer 35

• INR poorly predicts factor adequacy
• INR does not predict bleeding from procedures
• Bleeding usually follows vascular injury
• FFP is not indicated before procedures when INR is modestly elevated (<2) and perhaps not even when more elevation
• FFP use strongly associated with TRALI & TACO

Question 36

What were the results of the study:

Safety of lumbar puncture for children with acute lymphoblastic and thrombocytopenia

Answer 36

Prediction of bleeding - platelets < 20 (x10^9/L)
specificity = 0/199 = 0%
95% CI = 0-1.75
lumbar puncture pretty low risk even in severely thrombocytopenic patients. this study included children with few patients below 10, so still reasonable to transfuse prior to procedure if platelets are less than 10

Question 37

What are the broad guidelines for transfusing FFP and platelets based on INR and platelet counts?

Answer 37

INR > 2.5 = zone of prophylactic treatment

platelets < 30,000 = zone of prophylactic treatment