Transcript Transfusion Support Who Needs to be Transfused… and Who Does Not? Jerry E.

Transfusion Support
Who Needs to be Transfused…
and Who Does Not?
Jerry E. Squires MD, PhD
Department of Pathology and Laboratory
Medicine
Medical University of South Carolina
Allogeneic Whole Blood and Red Cell
Collection and Transfusion
Who Uses Blood?
The Decision to Transfuse:
A RISK / BENEFIT DECISION
What are these risks??
Risks of Transfusion
Risks of
Transfusion
TransfusionTransmitted
Infections
Transfusion
Reactions
MisTransfusion
Transfusion-Transmitted Infections
(TTI)
• The Potential List is LONG
–
–
–
–
–
–
–
• The Actual Risk is SMALL
HIV
HBV
HCV
HTLV
Syphilis
WNV
The “others:”
•
•
•
•
•
Chagas
Parvo B19
Malaria
Babesiosis
Etc., Etc., Etc.
– Hepatitis C 1:1,935,000
– Hepatitis B 1:400,000
– HIV
1:2,135,000
Transfusion-Transmitted Infections:
Risk Comparison
Transfusion Reactions
Reaction Type Predominant
Symptoms
Cause
Treatment/
Prevention
Prognostic
Frequency
Allergic
Urticaria
Type 1
Hypersensitivity
Antihistamine
No sequellae
1:100
Anaphylactic
Urticaria
Hypotension
(shock)
IgA Deficiency
Supportive / IgA
deficient
products or
washed
Must receive
IgA deficient
products
1:20,000
Febrile
Fever (>1oC)
Cytokines in
store products
Antipyretic
LR Products
No sequellae
1:300
TRALI
Resp. Distress
Pul. Edema
WBC/HLA aby in
donor product
Supportive
No sequellae
1:5000
TACO
Resp. Distress
Pul. Edema
Volume
Diuresis
Manage I/O
No sequellae
?????
Acute
Hemolytic
Fever
Pain
Hemolysis
Hypotension
Red Cell Aby
Patient/Sample
Identity
1:33,000
Mis-Transfusion
Serious Hazards of Transfusion (SHOT)
* Voluntary reporting system for
adverse reactions in UK
PTP (2)
0.3%
TRALI (23)
3.8%
TTI (3)
0.5%
DTR (28)
4.6%
ATR (68)
11.1%
IBCT (485)
79.6%
• IBCT????
– Wrong blood (18%)
• ABO, Rh, “luck”
– Pre-transfusion testing error (4.5%)
• Aby screen, DAT, wrong sample
– Transplant blood type error (0.5%)
• ABO error
– Error in specification (29%)
• Irradiation, CMV, Antigennegative
– Inappropriate transfusion (14%)
• Wrong component transfused
– Unsafe transfusion (16%)
• Improper storage, outdated
– RhIg administration error (18%)
• Late, wrong patient, outdate
Summary Transfusion Risks
Transfusion-Transmitted
Disease
Transfusion Reactions
Mis-Transfusion
•Overall risk of TTI now less
than 11.5/1,000,000
•Risk of HIV and HCV now
approximate 1:2,000,000
•Risk reduction is due to
donor screening and
testing improvements
•Allergic and febrile
reactions remain the most
common
•The risk of TRALI is now
approximately 1:5000 and
is the most common cause
of transfusion associated
death reported to the FDA
•Male predominant plasma
products reduce the risk of
TRALI
•Mis-transfusion due to
error is the most common
type of adverse transfusion
problem reported to
national hemovigilance
programs (~1 : 6000
transfusions)
•Most acute hemolytic
reactions resulting in death
result from ABO
incompatibility which is
usually due to mistransfusion
Are there any other transfusion risks?
• Typically, discussions of transfusion risk
centers on the 3 areas that have already been
mentioned:
– Transfusion Reactions
– Transfusion Transmitted Disease
– Mis-Transfusion
• But, is there another transfusion risk that
should be added into the risk / benefit
equation?
One More “Risk??”
• TRICC: Transfusion
Triggers in Critical Care
(Hebert PC et al, 1999)
– RCT (1994-1997)
– Liberal Txf arm:
• 420 patients
• Txf trigger 10.0 g/dL
– Restrictive Txf arm:
• 418 patients
• Txf trigger 7.0 g/dL
– Primary end-point: 30 day
mortality from all causes
Outcomes:
* 30-day mortality similar in both
arms
* Mortality advantage for
restrictive txf. for patient <55 y
or APACHE score 2 or less
One More “Risk?”
One More “Risk?”
Cancer Recurrence
Risks and Benefits
of Transfusion
• Every 2 seconds someone
in the US gets a
transfusion
• 30,000,000 blood
components are
transfused every year in
the US
• 4,500,000 people are
transfused in the US
every year
• 1 out of 7 hospital
admissions gets a
transfusion
So, in spite of the risks—
small though they may
be—we must think that
transfusion is providing
some BENEFIT to our
patients…..
Who Should Be Transfused?
• It is estimated that as many as 25% of the red
cell transfusions in the US are unnecessary.
• The question is not whether transfusion is
required in the care of many patients…
• The question is which patient should be
transfused; or in which patient will a
transfusion be potentially life-saving and in
which patient will a transfusion be lifeshortening?
Red Cell Transfusion
Red Cell Transfusion:
Who Needs It?
• Patient evaluation
– Organ ischemia (CV disease)
– Patient coagulopathy
• Laboratory evaluation
Hgb. < 6
Hgb. 6-10
Hgb.>10
• RC usually indicated
• RC used based on clinical setting
• RC rarely indicated
• Estimated blood loss
– Visual inspection of surgical field
– Sponge counts
– Suction
ASA Guidelines
Anesthesiology 2006
Red Cell Transfusion
Who Needs It?
• Methods to reduce RC use
– Anemia
• Tolerance of lower Hgb
• Pharmacologic approach
– One unit at a time
• Reduce “2-unit” transfusion orders without Hgb/Hct
• Joint Commission guidance
– Reduce blood draws
• Iatrogenic anemia (ICU patients ~45 mL/day)
Red Cell Transfusion
Final Considerations
• Evidence of benefit from RBC transfusion is hard to find
• Most benefit is assumed and not clinically proved
• Some patients benefit from blood transfusion, but we
need to do a better job of determining who they are
• Giving MORE blood is NOT better
• Many red cell transfusions are probably unnecessary
• Patients transfused when it is unnecessary get all the
RISK and NO BENEFIT
Platelet Transfusion
Platelet Transfusion:
Who Needs It?
• What do you hope to accomplish?
– To prevent or stop bleeding due to thrombocytopenia
• Practice Guidelines:
– Anesthesiology 2006; 105: 198-208
– “In surgical or obstetric patients with normal platelet
function, platelet transfusion is rarely indicated if the
platelet count is known to be greater than 100,000 X
109”
– “…and is usually indicated when the platelet count is
below 50 X 109”
Platelet Transfusion:
Who Needs It?
• Prophylactic Platelet Transfusion:
– Transfusion of platelets to non-bleeding patients
with “low” platelet counts—to prevent
thrombocytopenic hemorrhage
• The Questions:
– Is prophylactic platelet transfusion necessary?
– If so, what is a safe and effective platelet
transfusion trigger?
Platelet Transfusion:
Relationship Between Platelet Count and Bleeding
• Gaydos LA et al, 1962
– 92 nontransfused thrombocytopenic
patients
– % days with bleeding
• Slichter SJ and Harker LA, 1978
– 20 aplastic thrombocytopenic
patients
– Fecal blood loss
Platelet Transfusion:
Are Prophylactic Platelet Transfusions Necessary?
• Friedmann, AM et al (2002)
– Multiple logistic regression analysis of the frequency of
bleeding as a function of platelet count in 2942
thrombocytopenic patients
– Conclusion: first morning platelet count or lowest daily
platelet count did NOT correlate with bleeding frequency
• Wandt, H et al (2006)
– A comparison of therapeutic versus prophylactic platelet
transfusion in BMT patients
– Conclusion: therapeutic transfusion resulted in NO
increase in bleeding episodes (and reduced platelet use by
50%)
Platelet Transfusion:
Who Needs It?
• If prophylactic platelet transfusions are used in nonbleeding patients…
– What is a safe and effective platelet transfusion trigger?
1.
Rebulla P et al. 1997
–
–
–
2.
Adult patients with acute leukemia in first remission induction; randomized
into 2 groups:
Lower threshold: 10 X 109/ L
»
3.1% of days with significant bleed
»
21.5% decrease in plt use
Higher threshold: 20 X 109/L
»
2% of days with significant bleed
Wandt H et al. (2006)
–
–
–
105 pateints with acute leukemia; randomized into 2 groups:
Lower threshold: 10 X 109/L
»
17% of patients with bleeding complications
Higher threshold: 20 X 109/L
»
18% of patients with bleeding complications
Platelet Transfusion
Prophylactic Use—Invasive Procedures
• Slichter S 2007:
– “…the consensus of medical
opinion is that a plt count of
at least 50 X 109/L should be
maintained.”
– “Unfortunately there are no
definitive studies to
substantiate this plt
transfusion trigger.”
– “…patients with intracranial
bleeding and during and
following neurosurgical
procedures should have plt
counts maintained at >100 X
109/L”
• Platelet Transfusion in
Patients Undergoing Invasive
Procedures
Bishop et al (1987)
 95 patients with acute leukemia
undergoing 167 surgical
procedures
 70% of procedures were classified
as “major” (e.g. laparotomy,
thoracotomy, hip replacement, AK
amputation)
 Results: no procedure-related
deaths or excess bleeding when
the platelet count ≥ 50 X 109/L
Platelet Transfusion:
Summary Recommendations
• Current Platelet Transfusion Recommendations:
– Invasive procedures:
• 50,000/µL
• Neurologic procedures? (100,000/µL????)
– Prophylactic (nonbleeding patient):
• 10,000/µL
• Fever, Sepsis may benefit from a “higher” trigger
Platelet Transfusion:
Another Aspect of Bleeding Risk
• Hematocrit and Bleeding
Risk:
– Valeri et al, 2001
• The hematocrit may play a role
in bleeding risk particularly in
thrombocytopenic patients
• In normal volunteers,
plateletpheresis which reduced
platelet count significantly did
not affect bleeding time (right
bars)
• But the removal of red cells
reducing the Hct from 41% to
35%, almost doubled the
bleeding time
• Conclusion: maintain the Hct. In
thrombocytopenic patients
Plasma Transfusion:
Who Needs It?
• The US“love affair” with
plasma:
RBC and FFP Use in US (1982-2001)
Year
RBC
(X 106)
FFP
(X 106)
FFP :
RBC
1982
11.5
1.9
1 : 6.6
1989
12.1
2.2
1 : 5.5
1994
11.1
2.6
1 : 4.3
1999
12.4
3.3
1 :3.7
2001
13.9
3.9
1 : 3.6
Plasma Transfusion:
Who Needs It?
Annual RC and FFP Use
Country
RBC Unit
(X 103)
RBC Units
(per 1000
population)
FFP Units
(X 103)
FFP Units
(per 1000
population)
FFP:RBC
France
2,100
34.4
242
4.0
1 : 8.5
UK
2,700
45.3
385
6.5
1 : 7.0
US
13,900
49.5
3900
13.9
1 : 3.6
NZ
125
32.1
21.3
5.5
1 : 5.9
Plasma Transfusion:
Who Needs It?
American Society of Anesthesiologists
Practice Guidelines (1996):
1.
2.
3.
4.
5.
6.
Urgent reversal of Warfarin Therapy
Correction of known coagulation factor deficiencies when
specific concentrates are unavailable
Correction of microvascular bleeding in presence of
elevated (>1.5 x normal) PT or PTT
Correction of microvascular bleeding secondary to
coagulation factor deficiency in patients transfused with
more than one blood volume when PT and PTT cannot be
obtained promptly
FP should be given in doses calculated to achieve a
minimum of 30% of plasma factor levels
FP is contraindicated for augmentation of plasma volume
Why Is Plasma Ordered?
Plasma Transfusion:
Who Needs It?
• Assumptions in the Use of Plasma:
– Abnormalities of PT / INR correlate with the risk of
bleeding
– Plasma transfusion can correct the abnormal PT /
INR thereby reducing (or eliminating) the risk of
bleeding
Are these assumptions correct?????
Plasma Transfusion
Who Needs It?
• Does a prolonged PT (INR) correlate with a risk
of bleeding?
IT DEPENDS !!!!!
Plasma Transfusion:
Does the PT / INR Predict Bleeding Risk?
• Wahab OI et al, 2006
– Compared estimated blood
loss in 121 patients with
mildly elevated PT / INR
– Result: no correlation
between PT / INR and
blood loss
• Ewe K, 1981
– Compared liver bleeding
time to PT in patients
undergoing liver biopsy
– Result: no correlation
between PT and liver
bleeding time
Plasma Transfusion:
Does the PT / INR Predict Bleeding Risk?
Plasma Transfusion:
Does the PT / INR Predict Bleeding?
Why does the PT / INR Not predict
Bleeding?
Coagulation Factor
Hemostatic Levels
for Surgery (%)
Sensitivity of PT
Reagent (%)
II
20-30
28
V
20
52
VII
10
44
VIII
40
N/A
IX
30
N/A
X
20
49
Bottomline: the PT (INR) will be prolonged even when there are adequate
levels of coagulation factors to mediate normal hemostasis
Why does the PT / INR Not Predict
Bleeding?
• Can the PT (INR) be used as an indicator of
bleeding risk?
• Agarwal et al (2012)
– Method:
• 20 consecutive acute liver failure patients
• Measured PT, TEG, individual pro- and anti-coagulatant
factors, thrombin generation
Can the PT / INR Reliably Predict
Bleeding Risk?
• Agarwal et al 2012
– Results:
• PT significantly prolonged (50.7 s ±7.2) and did not
correlate with TEG results
• TEG: 20% hypocoagulable; 45% normal; 35%
hypercoagulable
• Reduction in plasma levels of BOTH procoagulants and
natural anticoagulants but a significant increase in
plasma Factor VIII and vWF
• NO bleeding and NO blood transfusions
Can the PT / INR Reliable Predict
Bleeding Risk?
• Agarwal et al (2012)
– Comments:
• “…the perception of a bleeding diathesis with progressive
ALF as indicated by standard clotting tests (PT) is not
substantiated by a more comprehensive assessment…using
TEG”
• TEG indicates a “more balanced” coagulation state in these
patients
• PT affected by VII, X, V, II, fibrinogen and does not assess
anticoagulant, platelet and endothelial contributions to
coagulation
Bottomline: Perhaps the PT (INR) while assessing coagulation
factor deficiencies in bleeding patients, but it may also give
an overly simplified assessment of bleeding risk
Plasma Transfusion
• Given that there is a question as to whether
Plasma Transfusion will actually PREDICT a
patient’s bleeding risk (especially at INR levels
<2)….
• What is the capacity of Plasma Transfusion to
CORRECT a prolonged PT / INR?
Plasma Transfusion:
Does Plasma Correct a Prolonged PT/INR?
• Youseef et al, 2003
– 80 patients with cirrhosis and elevated PT
– Indications for plasma:
• 41% prophylaxis
• 59% active bleeding
– Dose:
• 75% received 2-4 units
• 25% received >4 units
– Result: with plasma, 89% of patients failed to
correct PT
Plasma Transfusion:
Does Plasma Correct a Prolonged PT / INR?
• Holland LL and Brooks
JP, 2006
– In adult and pediatric
patients the lowering of
an INR less that 1.7 with
FFP infusion is minimal
Plasma Transfusion:
Does Plasma Correct a Prolonged PT/INR?
• Wahab OI et al, 2006
– 121 patients with a
mildly elevated INR (1.11.85)
– The transfusion of
plasma to patients with
mildly elevated PT / INR
results in partial
normalization of PT in a
minority of patients and
fails to correct the PT in
99% of patients
So, Should We Transfuse???
Transfuse
Transfuse
Thoughts to Leave You With
• All transfusions carry some risk, but the most
significant risks may be:
– Mis-transfusion
– Patient outcomes
• Your best guide to transfusion is the patient’s clinical
condition; laboratory values (hemoglobin, PT, INR,
platelet count) are of marginal use at best
• It is estimated that up to 25% of RBC transfusions are
unnecessary, the question therefore is not about
eliminating transfusion, but rather about choosing who
and when—when will transfusion save a life and when
might it shorten it!