Implementing Best Practices for Blood Management

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(No Transcript)
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Learning Objectives
After taking part in the workshop, participants
should be able to

• Outline the prevalence of anemia in medical and
  surgical patients
• List the potential clinical and pharmacoeconomic
  benefits of current blood management strategies
• Identify the risks associated with transfusion
• Determine the appropriate transfusion trigger in
  managing individual patients with anemia
• Develop and implement critical pathways for blood
  management based on current best practices and
  available critical pathways resources

3
Workshop Materials

• Workshop binder includes
• Presentation slides
• Samples of critical pathway implementation
  resources (eg, algorithms, pocket cards, posters,
  form letters)
• Champion sign-up form
• Breakout session worksheets
• CME/CE evaluations

4
Workshop Materials (cont.)

• Complimentary USB Flash Drive
• Presentation slides
• Sample critical pathways implementation resources
  such as
• Critical pathway algorithms
• Pocket cards
• Posters
• Templates and form letters
• Additional resources (eg, organizations to
  contact, Web site links for transfusion
  guidelines, suggested reading)

5
Breakout Sessions

• Please think about how the data presented today
  may impact your critical pathways for blood
  management
• During the breakout sessions, you will begin the
  process of developing or updating your blood
  management pathways
• There will be 3 breakout sessions
• Review the sample critical pathways in your
  binder and identify areas that may need
  modification at your institution (30 min)
• Identify barriers to implementing critical
  pathways at your hospital (15 min)
• Develop a plan of action to overcome barriers to
  implementation (15 min)

6
Blood An Emotional Topic

• the sweeping story of a substance that has been
  feared, revered, mythologized, and used in magic
  and medicine from earliest timesa substance that
  has become the center of a huge, secretive, and
  often dangerous worldwide commerce.
• From the publishers description of the book

Starr D. Blood An Epic History of Medicine and
Commerce. New York, NY HarperCollins Publishers
2000.
7
Blood Collection and Utilization in the US

• 15 million units of whole blood and RBCs donated
• 29 million units of blood components transfused
• Mean age of whole-bloodderived platelet units
• 3.16 days at transfusion
• 3.08 days for an apheresis platelet unit
• Average cost of RBC units increased by 30.8
  from 2002
• 135 hospitals canceled elective surgery on 1
  days because of blood inventory shortages

• US Dept of Health and Human Services. The 2005
  Nationwide Blood Collection and Utilization
  Survey Report. Available at http//portal.aabb.or
  g/apps/docs/05nbcusrpt.pdf. Accessed April 23,
  2007.

2004 statistics.
8
The 3 Pillars of Blood Management

• Optimizing the hemoglobin level by recognizing,
  detecting, and treating anemia in all clinical
  situations
• Understanding anemia and harnessing the
  physiology of it, making it tolerable while
  optimization occurs
• Having a consistent approach to blood conservation

9
Prevalence of Anemia
10
WHO Definition of Anemia vsHb Distribution in
the General Population
Anemia in Men Hb lt13 g/dL
Hb distribution in women13.3 ? 0.9 g/dL
3000
Hb distribution in men15.2 ? 0.9 g/dL
2500
2000
N40,000 (NHANES III, 1988-1994)
Frequency
1500
1000
500
0
10
10.5
11
11.5
12
12.5
13
13.5
14
14.5
15
15.5
16
16.5
17
17.5
18
Hb Level (g/dL)
World Health Organization. Geneva, Switzerland
2001. Dallman PR, et al. In Iron Nutrition in
Health and Disease. London, UK John Libbey Co
199665-74.
11
Prevalence of Anemia in Critically Ill Patients
Percentage of Critically Ill Patients With Anemia
Vincent JL, et al. JAMA. 20022881499-1507.von
Ahsen N, et al. Crit Care Med. 1999272630-2639.
12
Prevalence of Anemia at Admission Among Various
Patient Groups
Patient type Prevalence () Reference

• Wilson A, et al. Am J Med. 2004116(suppl
  7A)50S-57S.
• Shander A, et al. Am J Med. 2004116(suppl
  7A)58S-69S.
• Knight K, et al. Am J Med. 2004116(suppl
  7A)11S-26S.
• Belperio PS, et al. Am J Med. 2004116(suppl
  7A)27S-43S.

13
Incidence of Preoperative Anemia
30 25 20 15 10 5 0
65,788 patients (1980-2000) Preoperative
evaluation WHO anemia definition
MenWomen

20-30
31-40
41-50
51-60
61-70
71-80
81-90
gt90
Years
Reproduced with permission from Kulier A, Gombotz
H. Anaesthesist. 20015073-86.
14
Anemia A Potent Multiplierof Mortality
No HF, No CKD, No Anemia
1
Anemia Only
1.9
CKD Only
2.05
HF Only
2.86
CKD, Anemia
3.37
HF, Anemia
3.78
HF, CKD
4.86
HF, CKD, Anemia
6.07
0
1
2
3
4
5
6
7
Relative Risk of 2-Year Mortality
N 1.1 million (5 Medicare sample, 1996-1997)
Herzog CA, et al. Presented at 6th Annual
Scientific Meeting of the Heart Failure Society
of America September 22-25, 2002 Boca Raton,
Florida. Abstract 226.
15
Effects of Anemia Treatment on Renal Patients
Partial correction of anemia to Hb 11-12 g/dL in
patients with CKD may
Reduce morbidity, hospitalization, and
mortality1-3
Improve QOL,6,7 exercise capacity,8cognitive
function,2 and sexual function3
Improve LV structureand function4,5
1. Xia H, et al. J Am Soc Nephrol.
1999101309-1316. 2. Bedani PL, et al. Nephron.
200189350-353. 3. Wu SC, et al. Scand J Urol
Nephrol. 200135136-140. 4. Hayashi T, et al. Am
J Kidney DIs. 200035250-256. 5. Portoles J, et
al. Am J Kidney Dis. 199729541-548. 6. Revicki
DA, et al. Am J Kidney Dis. 199525548-554. 7.
Furuland H, et al. Nephrol Dial Transplant.
200318353-361. 8. Clyne N, et al. Nephron.
199260390-396.
16
An Introduction to Blood Management
17
Blood Management
Patient Centered

Appropriate Transfusion Medicine
Blood Conservation
18
Potential Benefits of Blood Management

• Addresses the issue of anemia
• Reduces patient exposure to allogeneic blood
• Improves patient outcome
• Helps with preserving current blood supplies
• Reduces costs
• Prepares for forthcoming pay-per-performance
  guidelines and other future regulatory issues

19
Strategies for Blood Management in Surgical
Patients

• Preoperative
• Reduce level at which transfusion is performed
• Increase preoperative RBC mass (EPO, iron)
• Preoperative autologous donation
• Intraoperative
• Meticulous hemostasis and operative technique
• Acute normovolemic hemodilution
• Blood salvage
• Postoperative
• Restricted phlebotomy
• Blood salvage

Adapted from Goodnough LT, et al. Transfusion.
200343668-676.
20

• Understanding the Physiology and Reserve of
  Anemia

21
Anemia Lower the Transfusion Trigger Point?

• Hb 7.0 g/dL-9.0 g/dL sufficient in critically ill
  patients
• Hébert PC, et al. N Engl J Med. 1999340409-417.
• Much lower Hb tolerated (gt5.0 g/dL) in
  nonstressed normal patients
• Weiskopf RB, et al. Anesthesiology.
  2000921646-1652.
• Patients with CAD may require Hb levels in
  slightly higher ranges (8.0 g/dL-9.0 g/dL) and
  avoid tachycardia
• ?-blockers
• Euvolemia
• Minimum, safe (optimal) Hb/Hct unknown
• Trigger can be lowered to avoid transfusions

22
Compensatory Mechanisms of Anemia

• Hb 6.0-7.0 g/dL tolerable (blood loss
  controlled good cardiac function)
• ? Cardiac output
• ? Coronary flow
• ? Blood viscosity
• ? O2 consumption
• ? O2 extraction

Corwin HL, Hébert PC. Physiology of anemia and
red blood cell transfusion. In Spiess BD, Spence
RK, Shander A, eds. Perioperative Transfusion
Medicine. 2nd ed. Philadelphia Lippincott
Williams Wilkins 2006chap 6.
23
Adaptation to Anemia

• Low Hb is well tolerated for short periods
• Maintenance of perfusion is required for
  tolerance of anemia
• High viscosity fluid (colloid) is better than
  crystalloid not albumin
• For severe anemia add high FIO2 to increase the
  dissolved portion of O2

24
Should the transfusion trigger in your
institution be revised?Discussion
25

• Pharmacologic Agents for the Treatment of Anemia

26
Erythropoietin Regulates Red Blood Cell
Production
Renal interstitial peritubular cells detect low
blood oxygen levels
EPO stimulates the proliferation and
differentiation of erythroid progenitors into
reticulocytes and prevents apoptosis
Erythropoietin (EPO) secreted into the blood
EPO
More reticulocytes enter circulating blood
Increased oxygen delivery to tissues
Reticulocytes differentiate into erythrocytes,
increasing the erythron size
Dessypris E. In Lee G, et al, eds. Wintrobes
Clinical Hematology. Vol 1. Baltimore, Md
Lippincott, Williams Wilkins
1998169-192. Bunn H. In Isselbacher K, et al,
eds. Harrisons Principles and Practice of
Internal Medicine. 13th ed. New York, NY
McGraw-Hill 19941717-1721.
27
Erythropoietic AgentsExogenous Erythropoietin

• Formulations
• Epoetin alfa (global)
• Epoetin beta, epoetin delta, epoetin omega
  (non-US, international)
• Darbepoetin alfa (novel erythropoiesis-stimulating
  protein with longer terminal half-life than
  epoetin alfa)
• Hematologic effects identical to endogenous
  erythropoietin
• Apoptotic agents neuro-/cardioprotection

28
FDA-Approved Indications for Erythropoiesis-Stimul
ating Agents

• Epoetin alfa (Procrit)1
• Treatment of anemia of chronic renal failure
  patients
• Treatment of anemia in zidovudine-treated
  HIV-infected patients
• Treatment of anemia in cancer patients on
  chemotherapy
• Reduction of allogeneic blood transfusion in
  surgery patients
• Darbepoetin alfa (Aranesp)2
• Treatment of anemia associated with chronic renal
  failure, including patients on dialysis and
  patients not on dialysis
• Treatment of anemia in patients with nonmyeloid
  malignancies where anemia is due to the effect of
  concomitantly administered chemotherapy

• Procrit (epoetin alfa) prescribing information.
  Raritan, NJ Ortho Biotech Products, LP 2007.
• Aranesp (darbepoetin alfa) prescribing
  information. Thousand Oaks, Calif Amgen Inc.
  2007.

29
Erythropoietin Dosing

• Use the lowest dose that will gradually increase
  the Hb concentration to the lowest level
  sufficient to avoid the need for RBC transfusion
• Darbepoetin alfa administration (starting dose)
• Chronic renal failure IV or SC as a single
  weekly injection
• Patients receiving chemotherapy SC weekly or
  once every 3 weeks
• Epoetin alfa administration (starting dose)
• Chronic renal failure IV or SC injection 3 x
  weekly
• Zidovudine-treated HIV-infected patients IV or
  SC injection 3 x weekly
• Cancer patients on chemotherapy SC 3 x weekly or
  weekly
• Surgery patients
• 300 U/kg/d SC for 10 days before surgery, on the
  day of surgery, and for 4 days after surgery or
• 600 U/kg SC once weekly (21, 14, and 7 days
  before surgery) plus a fourth dose on the day of
  surgery
• All patients should receive adequate iron
  supplementation

IV route is recommended for patients on dialysis.
Aranesp (darbepoetin alfa) prescribing
information. Thousand Oaks, Calif Amgen Inc.
3/2007. Procrit (epoetin alfa) prescribing
information. Raritan, NJ Ortho Biotech Products,
LP March 2007.
30
New Safety Information for ESAs

• Revised product labeling for Aranesp, Epogen,
  and Procrit includes a new boxed warning about
  using the lowest dose possible to avoid the need
  for blood transfusion because of the increased
  risk for death and serious cardiovascular events
  when administered to achieve a target Hb gt12 g/dL
  in cancer, renal failure, and surgical
  patients1-4
• In cancer patients, the use of ESAs
• Shortened the time to tumor progression in
  patients with advanced head and neck cancer
  receiving RT when administered to target a Hb gt12
  g/dL
• Shortened overall survival and increased deaths
  attributed to disease progress at 4 mo in
  patients with metastatic breast cancer receiving
  CT when administered to a Hb gt12 g/dL
• Increased the risk of death when administered to
  a target Hb gt12 g/dL in patients with active
  malignant disease receiving neither CT nor RT.
  ESAs are not indicated for this population

• US Food and Drug Administration Center for Drug
  Evaluation and Research. Information for
  Healthcare Professionals. Erythropoiesis
  stimulating agents (ESA) Aranesp (darbepoetin),
  Epogen (epoetin alfa), and Procrit (epoetin
  alfa). FDA alert 11/16/2006, updated 2/16/2007
  and 3/09/2007. Available at http//www.fda.gov/cd
  er/drug/InfoSheets/HCP/RHE2007HCP.htm. Accessed
  April 30, 2007.
• Aranesp (darbepoetin alfa) prescribing
  information. Thousand Oaks, Calif Amgen Inc.
  3/2007.
• Epogen (epoetin alfa) prescribing information.
  Thousand Oaks, Calif Amgen Inc. 3/2007.
• Procrit (epoetin alfa) prescribing information.
  Raritan, NJ Ortho Biotech Products, LP March
  2007.

31
Strategies for Primary and Secondary Prevention
of Venous Thromboembolism

• Pharmacologic1,2
• LMWH (eg, enoxaparin, dalteparin)
• Unfractionated heparin (UFH)
• Oral anticoagulants (eg, warfarin)
• Antiplatelet (eg, aspirin)
• Pentasaccharide (eg, fondaparinux)
• Direct thrombin inhibitors (eg, bivalirudin,
  argatroban)

• Mechanical1
• Intermittent pneumatic compression
• Graduated compression elastic stockings

1. Geerts WH, et al. Chest. 2004126(3
suppl)338S-400S. 2. Nutescu E, Racine E. Am J
Health-Syst Pharm. 200259S7-S14.
32
CMSs Final Coverage Determination for the Use of
ESAs in Cancer

• On July 30, 2007, CMS announced its final NCD for
  the use of ESAs in cancer and related neoplastic
  conditions. Tx is only reasonable and necessary
  under the following conditions
• The Hb level immediately prior to initiation or
  maintenance of ESA tx is lt10 g/dL (or HCT lt30)
• The starting dose for ESA tx is the recommended
  FDA label starting dose, no more than 150/U/kg 3
  x wk for epoetin and 2.25 µg/kg/wk for
  darbepoetin alpha. Equivalent doses may be given
  over other approved time periods
• Maintenance of ESA therapy is the starting dose
  if the Hb level remains lt10 g/dL (or HCT lt30) 4
  wk after initiation of therapy and the rise in Hb
  is ?1 g/dL (HCT ?3)

Centers for Medicare Medicaid Services (CMS).
Decision Memo for Erythropoiesis Stimulating
Agents (ESAs) for non-renal disease indications
(CAG-00383N). Available at https//www.cms.hhs.go
v/mcd/viewdecisionmemo.asp?id203. Accessed
September 20, 2007..
33
CMSs Final Coverage Determination for the Use of
ESAs in Cancer (cont.)

• For patients whose Hb rises lt1 g/dL (HCT rise
  lt3) compared to pretx baseline over 4 wk of tx
  and whose Hb remains lt10g/dL after 4 wk of tx (or
  HCT lt30), the recommended FDA label starting
  dose may be increased once by 25. Continued use
  of the drug is not reasonable and necessary if
  the Hb rises lt1 g/dL (HCT rise lt3) compared to
  pretx baseline by 8 wks of tx
• Continued administration of the drug is not
  reasonable and necessary if there is a rapid rise
  in Hb gt1 g/dL (HCT gt3) over 2 wk of tx unless
  the Hb remains below or subsequently falls to lt10
  g/dL (or HCT lt30). Continuation and
  reinstitution of ESA therapy must include a dose
  reduction of 25 from the previously administered
  dose
• ESA tx duration for each course of chemotherapy
  includes the 8 wk following the final dose of
  myelosuppressive chemotherapy in a chemotherapy
  regimen
• CMS has narrowed the scope of its final decision
  to make no NCD at this time on the use of ESAs in
  myelodysplastic syndrome

Centers for Medicare Medicaid Services (CMS).
Decision Memo for Erythropoiesis Stimulating
Agents (ESAs) for non-renal disease indications
(CAG-00383N). Available at https//www.cms.hhs.go
v/mcd/viewdecisionmemo.asp?id203. Accessed
September 20, 2007..
34
New Safety Information for ESAs (cont.)

• In patients receiving ESAs preoperatively for
  reduction of allogeneic RBC transfusions, a
  higher incidence of DVT was documented in
  patients not receiving prophylactic
  anticoagulation
• Antithrombotic prophylaxis should be strongly
  considered for such patients

• US Food and Drug Administration Center for Drug
  Evaluation and Research. Information for
  Healthcare Professionals. Erythropoiesis
  stimulating agents (ESA) Aranesp (darbepoetin),
  Epogen (epoetin alfa), and Procrit (epoetin
  alfa). FDA alert 11/16/2006, updated 2/16/2007
  and 3/09/2007. Available at http//www.fda.gov/cd
  er/drug/InfoSheets/HCP/RHE2007HCP.htm. Accessed
  April 30, 2007.
• Aranesp (darbepoetin alfa) prescribing
  information. Thousand Oaks, Calif Amgen Inc.
  3/2007.
• Epogen (epoetin alfa) prescribing information.
  Thousand Oaks, Calif Amgen Inc. 3/2007.
• Procrit (epoetin alfa) prescribing information.
  Raritan, NJ Ortho Biotech Products, LP March
  2007.

35
Conditions for Which CMS Proposed ESA Treatment
Not Reasonable and Necessary

• Any anemia in cancer or cancer treatment patients
  due to folate deficiency, B12 deficiency, iron
  deficiency, hemolysis, bleeding, or bone marrow
  fibrosis
• The anemia associated with the treatment of acute
  and chronic myelogenous leukemias (CML, AML), or
  erythroid cancers
• The anemia of cancer not related to cancer
  treatment
• Any anemia associated only with radiotherapy
• Prophylactic use to prevent chemotherapy-induced
  anemia
• Prophylactic use to reduce tumor hypoxia
• Patients with erythropoietin-type resistance due
  to neutralizing antibodies
• Anemia due to cancer treatment if patients have
  uncontrolled hypertension

Centers for Medicare Medicaid Services (CMS).
Decision Memo for Erythropoiesis Stimulating
Agents (ESAs) for non-renal disease indications
(CAG-00383N). Available at https//www.cms.hhs.go
v/mcd/viewdecisionmemo.asp?id203. Accessed
September 20, 2007.
36
ASH and ASCO Respond to the CMS Determination

• On August 8, 2007, ASH stated that it is
  particularly concerned about the third limitation
  because the new policy restricts coverage of ESAs
  when a patients Hb rises gt10 g/dL after the
  first 4 wk of therapy and has recommended that
  this be an area in which CMS should reconsider
  its policy
• On August 1, 2007, ASCO stated that it remains
  seriously concerned about many of the provisions
  in the new policy, including but not limited to
• The new policy restricts coverage of ESAs
  whenever a patients Hb goes gt10 g/dL, which is
  inconsistent with both the FDA-approved labeling
  and national guidelines
• For hypo- or nonresponders, the new policy allows
  for a 1-time dose escalation of 25, which is
  inconsistent with the FDA-approved label and
  national guidelines
• The new policy also states that if after any
  2-wk period of time Hb rises by gt1 g/dL, ESA tx
  should be discontinued (depending on the Hb
  level). This could result in patients needing to
  have weekly blood draws to assess the rate of Hb
  rise over any give 2-wk period
• ASCO will continue to pursue solutions to these
  issues with CMS, HHS, and Congress

• ASH statement on The Centers for Medicare
  Medicaid Services (CMS) national coverage
  determination (NCD) for coverage of
  erythropoiesis-stimulating agents (ESAs) for
  non-renal uses. August 8, 2007. Available at
  http//www.hematology.org/policy/news/08082007.cfm
  . Accessed September 20, 2007.
• ASCO Update on ESA Final National Coverage
  Decision. August 1, 2007. Available at
  http//www.asco.org/portal/site/ASCO/menuitem.c543
  a013502b2a89de912310320041a0/?vgnextoida353a59e3c
  124110VgnVCM100000ed730ad1RCRD. September 20,
  2007.

37
Recent FDA Actions for ESAs in Chronic Renal
Failureassociated Anemia

• On September 11, 2007, the FDAs Cardiovascular
  and Renal Drugs Advisory Committee and the Drug
  Safety and Risk Management Advisory Committee
  voted to reject setting a strict target Hb level
  for the use of ESAs in treating anemia associated
  with CRF
• The committees agreed that ESA dosages used to
  achieve the Hb levels in the Normal Hematocrit
  and CHOIR studies are sufficient to form the
  basis for ESA dosage recommendations
• The committees recommended additional label
  guidance and further analyses toward identifying
  and appropriately treating patients who exhibit a
  poor response to ESAs

U.S. Food and Drug Administration. Cardiovascular
and Renal Drugs and Drug Safety and Risk
Management Advisory Committee Meeting. September
11, 2007. Available at http//www.fda.gov/ohrms/d
ockets/ac/07/briefing/2007-4315b1-00-index.htm.
Accessed September 19, 2007.
38
Efficacy of Erythropoietin in Treating Patients
Undergoing Major Elective Orthopedic Surgery
60
N200
rHuEPO 300 U/kg SC
50
N208
N316
Placebo
40
Transfusions,
30
20
10
0
COPES1
Faris et al2
de Andrade et al3
Primary outcome event any transfusion or Hb
concentration lt8 g/dL.

• Canadian Orthopedic Perioperative Erythropoietin
  Study Group. Lancet. 19933411227-1232.
• Faris PM, et al. J Bone Joint Surg Am.
  199678A(suppl)62-72.
• de Andrade JR, et al. Am J Orthop.
  199625533-542.

39
Efficacy of Erythropoietin in Treating
Critically Ill Patients

Plt.002 Plt.001 Plt.01. Adapted with
permission from Corwin HL, et al. Crit Care Med.
1999272346-2350.
40
Antifibrinolytic and Hemostatic Medications

• Serine protease inhibitor
• Aprotinin
• Inhibits trypsin, plasmin, and kallikrein
• Lysine analogues
• e-aminocaproic acid/tranexamic acid
• Inhibit plasmin
• Desmopressin acetate (DDAVP)
• Recombinant activated human coagulation factor
  VII (rFVIIa)
• Topical hemostatic agents and tissue adhesives
  and sealants

41
Aprotinin Indications, Usage, and Warnings

• Indicated for prophylactic use to reduce
  perioperative blood loss and the need for blood
  transfusion in patients undergoing
  cardiopulmonary bypass in the course of CABG
  surgery who are at an increased risk for blood
  loss and blood transfusion
• Given by slow IV infusion an initial (test) dose
  should be administered before the loading dose
• Warnings
• Hypersensitivity or anaphylactic reactions
  higher risk on second exposure
• Renal dysfunction

Trasylol (aprotinin injection) prescribing
information. West Haven, Conn Bayer
Pharmaceuticals Corporation December 2006.
42
Aprotinin (Trasylol) Black Box Warning
Trasylol administration may cause fatal
anaphylactic or anaphylactoid reactions. Fatal
reactions have occurred with an initial (test)
dose as well as with any of the components of the
dose regimen. Fatal reactions have also occurred
in situations where the initial (test) dose was
tolerated. The risk for anaphylactic or
anaphylactoid reactions is increased among
patients with prior aprotinin exposure and a
history of any prior aprotinin exposure must be
sought prior to Trasylol administration. The
risk for a fatal reaction appears to be greater
upon re-exposure within 12 months of the most
recent prior aprotinin exposure. Trasylol should
be administered only in operative settings where
cardio-pulmonary bypass can be rapidly initiated.
The benefit of Trasylol to patients undergoing
primary CABG surgery should be weighed against
the risk of anaphylaxis associated with any
subsequent exposure to aprotinin.
Trasylol (aprotinin) prescribing information.
Bayer Pharmaceuticals Corporation December 2006.
43
Risk Associated With Aprotinin Use in Cardiac
Surgery

• Recent observational studies show that, compared
  with the use of aminocaproic acid or tranexamic
  acid or no drug, aprotinin use among patients
  undergoing CABG surgery is associated with
• Increased perioperative risk of acute renal
  failure, myocardial infarction/heart failure, and
  stroke/encephalopathy1
• Increased risk of late mortality2
• Investigators advise against further use of
  aprotinin because safer and less expensive
  alternatives are available1,2
• Such studies using propensity-adjusted,
  multivariable logistic regression analysis may
  reflect selection, site-level, and other biases3

• Mangano DT, et al. N Engl J Med.
  2006354353-365.
• Mangano DT, et al. JAMA. 2007297471-479.
• Ferguson TB Jr. JAMA. 2007297527-529.

44
Desmopressin (DDAVP)

• Synthetic analogue of vasopressin
• ? Plasma levels of factor VIII and von Willebrand
  factor in deficient and healthy patients
• ? Platelet adhesion to the vessel wall (no effect
  on platelet count or aggregation)
• ? PTT and bleeding time
• Action not understood
• Now reserved for mild to moderate von Willebrand
  disease and uremic platelet dysfunction
• Not useful in cardiac surgery
• When given rapidly, may cause flushing,
  hypotension, and increased heart rate

Levy JH. Pharmacological approaches to prevent or
decrease bleeding in surgical patients. In
Spiess BD, Spence RK, Shander A, eds.
Perioperative Transfusion Medicine. 2nd ed.
Philadelphia Lippincott Williams Wilkins
2006chap 30.
45
Vitamin K Therapy

• IV is faster than SC or PO
• 1-10 mg IV effective dose slow infusion to
  handle vasodilatation or anaphylaxis
• Prothrombin time will begin to correct within 6
  hours and is usually normal within 24 hours
• Fresh frozen plasma (FFP) can be used for more
  rapid correction
• rFVIIa studies for warfarin reversal now under
  way

46
Recombinant Factor VIIa

• Produced by baby hamster kidney cell lines and
  free of human protein
• Initiates hemostasis through the tissue
  factordependent coagulation pathway
• Enhances coagulation at the site of injury
• Indicated for bleeding episodes and surgical
  bleeding in patients with
• Hemophilia A or B with inhibitors
• Factor VII deficiency

47
Off-label Use of rFVIIa

• Trauma
• Hepatic failure
• Postprocedure bleeding (tooth extraction)
• Prior to liver transplantation
• Prior to invasive procedures (liver biopsy, GI
  endoscopy, ethanol injection)
• Reversal of warfarin effect
• Upper GI bleeding
• Platelet dysfunction
• Cardiac surgery
• Intracranial hemorrhage

48
Adjuvant Agents

• While treating patients with epoetin, provide
  simultaneous treatment with
• Iron
• Folic acid
• Vitamin B12

49
Distribution of Iron in Tissue
Dietary iron
Duodenum (average, 1-2 mg per day)
Utilization
Utilization
Plasma transferrin (3 mg)
Bone marrow (300 mg)
Muscle (myoglobin) (300 mg)
Circulating erythrocytes (hemoglobin) (1800 mg)
Storage iron
Liver parenchyma (1000 mg)
Reticulo- endothelial macrophages (600 mg)
Adapted with permission from Andrews NC. N Engl J
Med. 19993411986-1995.
50
Functional Iron Deficiency

• An imbalance between the iron needs of the
  erythroid marrow and the iron supply, which is
  not maintained at a rate sufficient to allow
  normal hemoglobinization of the erythrocytes
• Leads to reduced reticulocyte and erythrocyte
  cellular Hb content
• Characterized by both low transferrin saturation
  concentration and serum iron despite normal or
  elevated iron stores
• Diagnosis may be based on measurement of the
  proportion of hypochromic erythrocytes (HYPO) and
  examination of erythrocyte hemoglobinization
  using the reticulocyte Hb content (CHr) test

Scigalla P, et al. Contrib Nephrol.
19908255-64.Mcdougall IC, et al. Br Med J.
198929157-158.Thomas C, Thomas L. Clin Chem.
2002481066-1076.Mittman N, et al. Am J Kidney
Dis. 199730912-922.
51
Causes of Iron Deficiency

• Inadequate iron absorption
• Increased blood loss
• Gastrointestinal blood loss (eg, epistaxis,
  varices, gastritis, ulcer, tumor, IBD)
• Genitourinary blood loss (menorrhagia, cancer,
  chronic infection)
• Pulmonary blood loss (pulmonary hemosiderosis,
  infection)
• Other blood loss (trauma, excessive phlebotomy,
  large vascular malformations)

Andrews NC. N Engl J Med. 19993411986-1995.
52
Efficacy of IV Iron Therapy

• Quickly replenishes depleted iron stores
• Raises serum ferritin
• Corrects iron-deficient erythropoiesis
• Raises transferrin saturation (TSAT) and Hb
  reticulocyte content (CHr)
• Increases Hb, or decreases epoetin dose for same
  Hb
• Maintains iron-sufficient erythropoiesis
• Replenishing iron stores assures adequate iron
  supply in patients prone to blood loss(eg,
  hemodialysis-related)

53
Current Status of Intravenous Iron Therapy
Absolute iron deficiency is defined as ferritin
lt200 µg/L and/or iron saturation lt20, or
relative iron deficiency (ferritin lt400 µg/L in
dialysis patients receiving erythropoietin
therapy, or the presence of gt10 hypochromic
erythrocytes and/or reticulocytes).
54
FDA-Approved Indications for IV Iron Therapy

• Iron dextran injection, USP1,2
• Patients with documented iron deficiency in whom
  oral administration is unsatisfactory or
  impossible
• Black box warning regarding risk of fatal
  anaphylactic-type reactions
• Sodium ferric gluconate complex in sucrose
  injection3
• Iron deficiency anemia in patients undergoing
  chronic hemodialysis who are receiving
  supplemental epoetin therapy
• Iron sucrose injection, USP4
• Iron deficiency anemia in
• Nondialysis dependent-chronic kidney disease
  (NDD-CKD) patients receiving or not receiving an
  erythropoietin
• Hemodialysis dependent-chronic kidney disease
  (HDD-CKD) patients receiving an erythropoietin
• Pentoneal dialysis dependent-chronic kidney
  disease (PDD-CKD) patients receiving an
  erythropoietin

• Dexferrum (iron dextran injection, USP) full
  prescribing information. Shirley, NY American
  Regent Laboratories, Inc.
• INFeD (iron dextran injection, USP) full
  prescribing information. Morristown, NJ Watson
  Pharma, Inc.
• Ferrelecit (sodium ferric gluconate complex in
  sucrose injection) full prescribing information.
  Corona, Calif Watson Pharma, Inc.
• Venofer (iron sucrose injection, USP) full
  prescribing information. Shirley, NY American
  Regent Laboratories, Inc.

55
Dosing of Available Intravenous Iron Agents

• Iron dextran (Dexferrum, INFeD)
• Follow table and formula in PI for estimating
  total iron required
• Sodium ferric gluconate complex in sucrose
  (Ferrlecit)
• Recommended dosage is 10 mL (125 mg of elemental
  iron) may be diluted in 100 mL of 0.9 NaCl
  administered by IV infusion over 1 h or
  administered undiluted as a slow IV injection (at
  a rate of up to 12.5 mg/min)
• Iron sucrose (Venofer)
• HDD-CKD Administered undiluted as a 100 mg slow
  IV injection over 2-5 min or as an infusion of
  100 mg, diluted in a maximum of 100 mL of 0.9
  NaCl over at least 15 min (total dose, 1000 mg)
• NDD-CKD Administered as a total cumulative dose
  of 1000 mg over 14 days as a 200 mg slow IV
  injection over 2-5 min on 5 different occasions
  within the 14-day period

• Dexferrum (iron dextran injection, USP) full
  prescribing information. Shirley, NY American
  Regent Laboratories, Inc.
• INFeD (iron dextran injection, USP) full
  prescribing information. Morristown, NJ Watson
  Pharma, Inc.
• Ferrelecit (sodium ferric gluconate complex in
  sucrose injection) full prescribing information.
  Corona, Calif Watson Pharma, Inc.
• Venofer (iron sucrose injection, USP) full
  prescribing information. Shirley, NY American
  Regent Laboratories, Inc.

56
Preoperative Iron Supplementation in Colorectal
Cancer Patients

• Cohort of 569 patients undergoing colorectal
  cancer surgery
• 32 patients with Hb 10 g/dL and 2 weeks of
  preoperative iron treatment (200 mg)
• 84 patients with Hb 10 g/dL without iron
  treatment (controls)
• Results Increase in Hb by 2 g/dL in iron treated
• Transfusion rate 9 in iron treated vs 27
  without iron treated

Okuyama M, et al. Surg Today. 20053536-40.
57

• Reducing Blood Loss During Surgery

58
Strategies for Reducing Blood Loss During Surgery

• Careful surgical dissection and hemostasis
• Use of controlled hypotensive anesthesia1
• Maintenance of normothermia1
• Blood cell salvage1
• Tolerance of normovolemic anemia1
• Elevating the surgical site2

• Gil O, et al. Ann Thorac Surg. 1995601160-1161.
• Park CK. Anesth Analg. 200091552-557.

59
Cell Salvage Technique

• Collected blood is citrated, filtered, washed
  with saline, concentrated, and returned to the
  patient
• Efficacy and quality are directly dependent on
  the skill of the operator and the processes
  established
• Contamination by amniotic fluid, malignant cells,
  or bacteria is a relative contraindication

Waters JH. Perioperative red cell salvage and
autotransfusion. In Spiess BD, Spence RK,
Shander A, eds. Perioperative Transfusion
Medicine. 2nd ed. Philadelphia Lippincott
Williams Wilkins 2006chap 33.
60
General Indications for Cell Salvage

• Anticipated blood loss is 20 of the patients
  estimated blood volume1
• Blood would ordinarily be cross-matched1
• More than 10 of patients undergoing the
  procedure require transfusion1
• The mean transfusion for the procedure exceeds 1
  unit1
• Other2
• Religious beliefs, patient preference
• Compatible donor blood unavailable
• Adequate preoperative autologous donation not
  possible
• Unexpected blood loss
• Red cell antibodies

• Guidelines for blood recovery and reinfusion in
  surgery and trauma. American Association of Blood
  Banks Autologous Transfusion Committee 1996-1997
  Committee. Bethesda, Md American Association of
  Blood Banks 1997.
• Waters JH. Perioperative red cell salvage and
  autotransfusion. In Spiess BD, Spence RK,
  Shander A, eds. Perioperative Transfusion
  Medicine. 2nd ed. Philadelphia Lippincott
  Williams Wilkins 2006chap 33.

61
Potential Cell Salvage Surgical Procedures

• Cardiac
• Valve replacement, redo bypass grafting
• Orthopedic
• Major spine, bilateral knee replacement, revision
  hip replacement
• Urology
• Radical retropubic prostatectomy, cystectomy,
  nephrectomy
• Neurosurgery
• Giant basilar aneurysm
• Vascular
• Thoracoabdominal/abdominal aortic aneurysm repair
• Liver transplant

Adapted from Waters JH. Perioperative red cell
salvage and autotransfusion. In Spiess BD,
Spence RK, Shander A, eds. Perioperative
Transfusion Medicine. 2nd ed. Philadelphia
Lippincott Williams Wilkins 2006chap 33.
62
Potential Complications of Cell Salvage

• Air embolism
• Hypertension due to incomplete elimination of
  epinephrine/norepinephrine
• Hypertension/tachycardia due to incomplete
  elimination of oxymetazoline
• Loss of salvaged blood

Waters JH. Perioperative red cell salvage and
autotransfusion. In Spiess BD, Spence RK,
Shander A, eds. Perioperative Transfusion
Medicine. 2nd ed. Philadelphia Lippincott
Williams Wilkins 2006chap 33.
63
Acute Normovolemic Hemodilution

• Whole blood is withdrawn immediately before or
  after anesthesia is initiated and is replaced
  with crystalloid/colloid to maintain normovolemia
• The blood is stored at room temperature in the
  operating room for up to 4 h (up to 24 h with
  refrigeration) and reinfused after bleeding
  ceases or if the patient has an unacceptably low
  Hb level
• Procedure results in?O2 carrying capacity?
  Blood viscosity? SNS stimulation? VR, stroke
  volume, cardiac output? Number of RBCs lost
  during surgery

64
Acute Normovolemic Hemodilution Calculating
Blood Withdrawal

• How much volume of blood can be drawn?
• Usually limited to a volume of 2000 mL or a
  target hematocrit of 28, whichever comes first
• Hb will decrease approximately 1 g/dL for each
  unit of blood removed
• Formula frequently used for determining amount of
  blood to be withdrawn to reach desired Hct
• V EBV ? Hcti Hctf / Hctav
• Hb of 7.0 g/dL is also used
• No agreed-upon standards

EBV estimated blood volume Hctav hematocrit
average during the hemodilution process Hctf
final desired hematocrit Hcti initial
hematocrit V volume of blood to be withdrawn.
Shander A, Rijhwani T. Intraoperative acute
normovolemic hemodilution. In Spiess BD, Spence
RK, Shander A, eds. Perioperative Transfusion
Medicine. 2nd ed. Philadelphia Lippincott
Williams Wilkins 2006chap 34.
65
Acute Normovolemic Hemodilution Potential
Patient Selection Criteria

• Estimated blood loss 1500 mL
• Preoperative Hb concentration 12 g/dL after
  correction of normovolemia
• Normal cardiovascular function (ie, no ischemic
  signs, no ST-segment changes)
• Absence of
• Renal, lung, or other disease or infection
• Untreated hypertension and liver cirrhosis
• Coagulation abnormalities
• Patients who have a type and crossmatch for
  surgery

Kreimeier U, Messmer K. World J Surg.
1996201208-1217. Shander A, Rijhwani T.
Intraoperative acute normovolemic hemodilution.
In Spiess BD, Spence RK, Shander A, eds.
Perioperative Transfusion Medicine. 2nd ed.
Philadelphia Lippincott Williams Wilkins
2006chap 34.
66
Acute Normovolemic Hemodilution Safety
Considerations

• The safety of ANH has been demonstrated in
  cardiac,1,2 vascular,3 orthopedic,4,5 urologic,6
  and general operations7 but no consensus has been
  established
• An ANH program must comply with AABB standards
• Blood must be properly stored and labeled for
  autologous use only
• Minimizes the possibility of clerical error or
  bacteria contamination

• Boldt J, et al. J Cardiothorac Vasc Anesth.
  1991523-28.
• Johnson RG, et al. J Cardiothorac Vasc Surg.
  1992104307-314.
• Kramer AH, et al. Surg Gynecol Obstet.
  1979149831-836.
• Martin E, Ott E. Bibl Haematol. 198147322-337.
• Hur SR, et al. Spine. 199217867-873.
• Ness PM, et al. Transfusion. 199232226-230.
• Laks J, et al. Ann Surg. 1974180103-109.

67
Acute Normovolemic Hemodilution Cost and Other
Considerations
Cost savings

• ANH is equivalent to PAD but without wastage or
  inventory and testing cost
• Reduction in total transfusion costs (100/unit
  with ANH compared with 269 with PAD)
• Time consuming
• Requires additional equipment/knowledge
• Some studies suggest that significant benefit
  (including economic) only for revision hip
  surgery and radical prostatectomy

Underutilized?
68
Other Intraoperative Strategies

• Hypervolemic hemodilution
• No blood is withdrawn
• Blood volume is expanded aggressively
• Decreased number of RBCs lost during surgery
• Postoperative diuresis and recovery
• Regional anesthesia
• Epidurals performed for orthopedic procedures
  including hip and knee

69
Other Intraoperative Strategies (cont.)

• Controlled hypotension
• MAP 50-65 mm Hg
• Do not use if the patient has CVS, CNS, renal,
  or liver dysfunction
• Controlled hypothermia
• O2 consumption is decreased 6 for each C
• Increased O2 solubility in the plasma via a left
  shift of the oxyhemoglobin dissociation curve
• Must maintain temperature gt33 C (arrhythmia,
  coagulopathy)

70
Other Intraoperative Strategies (cont.)

• Hemoglobin-based oxygen carriers
• Can augment tissue oxygen delivery and may
  decrease RBC transfusions
• Variety of products each has its own limitations
  and advantages
• Currently under experimental and clinical
  investigation
• Perfluorocarbon emulsions
• Possess a unique ability for enhanced gas
  solubility
• Shown to improve hepatocellular injury after
  hemorrhagic hypotension compared with use of
  blood, colloid, or combination of blood and
  colloid

Hare GMT, Mazer CD. Hemoglobin-based oxygen
carriers. In Spiess BD, Spence RK, Shander A,
eds. Perioperative Transfusion Medicine. 2nd ed.
Philadelphia Lippincott Williams Wilkins
2006chap 19.Spahn DR, et al. Anesthesiology.
2002971338-1349.
71
Hemostatic Surgical Instruments

• Electrocautery (thermal cautery)
• An electric current is used to heat a treatment
  instrument or probe
• The heated probe cauterizes capillary vessels and
  small arteries, minimizing blood loss
• Lasers
• Laser energy is used to cut, vaporize, and
  simultaneously coagulate a targeted area without
  disrupting adjacent tissue
• Cutting is achieved hemostatically, making
  systems suitable for endoscopic and open-surgical
  procedures
• Promote clotting by localizing heat in bleeding
  vessels, resulting in coagulation

72
Hemostatic Surgical Instruments (cont.)

• Microwave scalpel
• Concentrates a localized high-power microwave
  field around the leading edge of a scalpel blade
• Since microwave energy is absorbed in tissue, can
  provide in-depth coagulation during surgery on
  vascular organs such as the spleen and liver
• Argon-beam coagulator
• Uses a beam of ionized argon gas (argon plasma)
  to conduct a high-frequency electric current to
  bleeding tissues with limited tissue contact
• Can be used for hemostasis of surface, diffuse
  bleeding from parenchymatous tissues (eg, of the
  liver, spleen)

73
Postoperative Strategies

• Minimize phlebotomy
• Cell salvage
• Treatment with erythropoietin and iron
• Decrease CMRO2
• Sedation, analgesia
• Positive pressure ventilation, muscle relaxation
• Controlled hypothermia

74
Question-and-Answer Session
75
Blood Transfusion
76

• Blood Transfusion

Patient blood management has been lost in
transfusion Axel Hofmann, Economist
77
Potential Candidates for Transfusion

• Patients undergoing
• Cardiopulmonary bypass or cardiac surgery
• Urgent or emergent procedures
• Obstetric procedures
• Organ transplantation
• Major noncardiac surgery
• Patients with pre-existing blood disorders or
  acquired deficiency secondary to massive bleeding
• Critically ill patients

American Society of Anesthesiologists Task Force
on Perioperative Blood Transfusion and Adjuvant
Therapies. Anesthesiology. 2006105198-208.
78
Transfusion Risks/Complications

• Transfusion-related immunomodulation (TRIM)
• Systemic inflammatory response syndrome (SIRS)
• Transfusion-related acute lung injury (TRALI)
• Viral and bacterial transmission
• Increased nosocomial infection
• Increased mortality
• Administrative errors
• Acute transfusion reactions
• Stored donor blood The Cold Storage Lesion
• Free hemoglobin

79
Serious Hazards of Transfusion (SHOT), 2005
DTR (28) 4.6
TRALI (23) 3.8
TTI (3) 0.5
PTP (2)0.3
ATR (68) 11.2
IBCT (485) 79.6
N609
ATR acute transfusion reaction DTR delayed
transfusion reaction IBCT incorrect blood
component transfused PTP posttransfusion
purpura TRALI transfusion related acute lung
injury TTI transfusion transmitted
infection.Serious Hazards of Transfusion Annual
Report 2005. Available at http//www.shotuk.org/
SHOT20report202005.pdf. Accessed April 24, 2007.
80
Transfusion Errors

• Mistransfusion estimated
• 114,000 RBC units in the US1
• 128,000 RBC units in the UK2
• 10 labeling error 11,000 samples
• 25 lab error
• Remainder clinical setting
• Fatality exceeds HIV-related transmission by 4-
  to 8-fold

• Williamson LM, et al. BMJ. 199931916-19.
• Sazama K. Transfusion. 199030583-590.

81
Transfusion-related Acute Lung Injury (TRALI)

• Incidence estimates vary1
• Difficulty in ruling out left atrial hypertension
  (eg, transfusion-associated circulatory overload
  TACO, congestive heart failure) as cause
• Characteristics of acute lung injury
  indistinguishable from TRALI
• Lack of agreement on case definition
• Lack of awareness, underreporting/underdiagnosis
  of TRALI
• Leading cause of transfusion-related mortality1
  (1200,000 cases2)
• Proposed mechanisms
• Passively transfused donor HLA class I/II or
  neutrophil antigens3
• Mixture of predisposition and infusion of
  blood-related lipid-derived mediators4,5

• Kleinman S. Transfusion. 2006461465-1468.
• Holness L. Available at http//www.fda.gov/ohrms/
  dockets/ac/04/transcripts/2004-4057t1.htm.
  Accessed May 22, 2007.
• Popovsky MA, Moore SB. Transfusion.
  198525573-577.
• Silliman CC, et al. Vox Sang. 199263133-136.
• Silliman CC, et al. Transfusion. 199737719-726.

82
Blood Components Associated With TRALI

• Significant reported
• Whole blood
• RBC
• FFP
• Apheresis platelets
• Whole-bloodderived platelet

• Isolated
• WBC
• IVIG
• Cryoprecipitate
• Stem cells

FFP fresh frozen plasma IVIG IV immune
globulin RBC red blood cells WBC white
blood cells.
Shander A, Popvsky MA. Chest. 2005128598-604.
83
Potential and Current Infectious Risks to the
Blood Supply

• Simian foamy virus (SFV)
• HHV-8
• West Nile virus
• Chagas
• nCJD
• Malaria
• SARS
• Influenza

84
Bacterial Infections

• Risk of bacterial sepsis in red cells and
  platelet 13000 units transfused
• Sepsis develops in 125,000 units of platelets
  and 1250,000 units of RBCs transfused
• Bacterial detection performed early will miss
  late infection (platelets)
• Pathogen inactivation, is that the answer?

Blajchman MA, et. al. Transfus Med Rev.
200519259-272.
85
Decline in Risks of Transfusion-Transmitted HIV,
HBV, HCV, and Bacterial Infections
1983 1985 1987 1990 1996 1999 2003 2004 Revised
HIV Non-A, non-B HCV p24 HCV and HIV West
Nile Bacterial donor antibody hepatitis antibody
antigen nucleic acid virus nucleic screening def
erral screening surrogate screening testing testin
g acid testing of platelets criteria testing
Adapted with permission from Blajchman MA,
Vamvakas EC. N Engl J Med. 20063551303-1305 and
Busch MP, et al. JAMA. 2003289959-962.
86
Acute Transfusion Reactions

• Anaphylaxis
• 110,00011500-3000 transfusions (platelets)
• IgA-mediated, IgA-deficient recipient
• Fatal up to 5
• Transfusion-associated circulatory
  overload(TACO) 13000 for all products
• Other immune- and antibody-mediated reactions

87
Donor Leukocytes

• Persistence of donor WBCs in trauma patients for
  up to 1.5 years after an allogeneic blood
  transfusion
• 2 x 109 WBCs in one unit of packed red blood
  cells
• 1 x 108 WBCs centrifuged, buffy-coat depleted
• 1-5 x 106 WBCs leukocyte filter,
  leukocyte-depleted

Lee TH, et al. Blood. 1999933127-3139.
88
The Cold Storage Lesion
Offner PJ, et al. Arch Surg. 2002137711-717.Bro
wn M, Whalen PK. Crit Care Nurse.
200020(suppl)1-14. Zallen G, et al. Shock.
20001329-33.
89
Age of Blood
90
Transfusion-related Immunomodulation (TRIM)

• Allogeneic blood transfusion
• Infuses recipient with potentially
  immunomodulatory substances foreign cells,
  cell-associated soluble antigens, biological
  response modifiers
• Human studies (controversial and hotly debated)
  suggest ABT (vs no transfusion/autologous
  transfusion)
• Positive effects ? renal allograft survival ?
  risk of recurrent abortion ? recurrence of
  Crohns disease
• Negative effects ? recurrence rate of resected
  malignancies ? post-op bacterial infections ?
  mortality
• TRIM effect thought to be due to leukocytes
• Animal data
• Strong signal in human data

91

• Outcome Measures
• Transfusion, Immune Modulation Infection, and
  Death

92
Effect of Blood Transfusion on Long-term Survival
After Cardiac Surgery
1.00
No XFN n546
0.95
Survival
0.90
XFN n546
0.85
0
48
60
36
12
24
Months after CABG
Kaplan-Meier estimates of survival based on equal
propensity scores of any transfusion (XFN) versus
no transfusion (No XFN).
CABG coronary artery bypass grafting.
Figure reproduced with permission from Engoren
MC, et al. Ann Thorac Surg. 2002741180-1186.
93
Nosocomial Infections in the ICU
Overall
18
Plt.005
Transfused patients
Nontransfused patients
15.4
16
12
Percentage of Patients
8
5.9
2.9
4
0
N1717
n416
n1301
Reproduced with permission from Taylor RW, et al.
Crit Care Med. 2002302249-2254.
94
Nosocomial Infections in the ICU
Overall
18
Plt.0001
Transfused patients
Nontransfused patients
16
14.3
N2085
12
Percentage of Patients
7.5
8
5.8
4
0
157/2085
61/428
96/1557
Reproduced with permission from Taylor RW, et al.
Crit Care Med. 2006342302-2308.
95
Transfusions Correlate With Infections in a
Dose-Dependent Manner
1.2
0-15 Units of PRBC
1.0
Y 0.1375e0.1187x R2 0.7566
0.8
Incidence of Infection
0.6
0.4
0.2
0.0
0
2
4
6
8
10
12
14
16
Transfusions
Reproduced with permission from Claridge JA, et
al. Am Surg. 200268566-572.
96
Association Between Allogeneic Blood Transfusion
and Mortality
Odds ratio 60-90 d mortality in OHS studies (all
European)2-4
0.1
1
10
100

• Meta-analysis, RCTs WBC-containing transfusions
  and mortality1
• No association detected across clinical settings
• Association may exist in open heart surgery
  (OHS)2-4

van de Watering et al
Bilgin et al
Wallis et al
Summary OR
Figure adapted with permission from Vamvakas EC.1

• Vamvakas EC. Transfusion. 200343963-973.
• Van de Watering LM, et al. Circulation.
  199897562-568.
• Bilgin YM, et al. Circulation. 20041092755-2760.
  
• Wallis JP, et al. Transfusion. 2002421127-1134.

97
Quality and Outcomes

• Evidence is compelling that blood transfusion is
  associated with the risk of significant
  morbidity, including
• Bacterial contamination1
• Transfusion-related acute lung injury (TRALI) and
  other immunologic reactions2
• Immunomodulatory effects (eg, TRIM)3
• Circulatory effects (eg, TACO)4
• Transfusion also is associated with increased
  short- and long-term mortality rates5

• Blajchman MA, et al. Transfus Med Rev.
  200519259-272.
• Kleinman S. Transfusion. 2006461465-1468.
• Blajchman MA. Hematology. 200510(suppl
  1)208-214.
• Langenfeld JE, et al. Surgery. 1994116859-867.
• Spiess BD, et al. Transfusion. 2004441143-1148.

98

• Preoperative Autologous Donation

99
Preoperative Autologous Donation

• Considered the standard of care for large-joint
  orthopedic surgery
• Expensive high cost of procurement, processing,
  wastage, and discarding
• Only 1 of every 2 donated units transfused
• PAD blood is banked and carries same risk of
  clerical error or misidentification as all banked
  blood
• Units of PAD blood have same functional
  impairments as other cold-stored blood
• PAD blood may not help patients avoid exposure to
  allogeneic blood
• 50 of patients who undergo PAD arrive anemic the
  day of surgery and require reinfusion of
  autologous blood as well as allogeneic
  transfusion to tolerate surgery

Etchason J, et al. N Engl J Med.
1995332719-724. Cohen JA, et al. Transfusion.
199535640-644.
100
Preoperative Autologous Donation
Contraindications

• Relative Contraindications
• Previous infarction
• Cerebrovascular insufficiency
• Hepatic failure
• Anticoagulant treatment in progress (with
  inhibitors of vitamin K)
• Absolute Contraindications
• High fever
• Documented or probable bacteremia
• Uncorrected hypovolemia
• Acute hepatic failure
• Cardiopathies (arrhythmias, angina, low
  cardiogenic output)
• Generally poor condition

101
Blood Product Transfusions

• The Traditional Concept
• Blood products are an effective therapeutic
  intervention
• The New Concept
• Transfusion of blood products is an undesirable
  outcome

L.T. Goodnough, MD
Red-cellcontaining components should not be
used to treat anemias that can be corrected with
specific medications such as iron, vitamin B12,
folic acid, or erythropoietin. Circular of
Information for the Use of Human Blood and
Components. Bethesda, Md American Association of
Blood Banks, Americas Blood Centers, and
American Red Cross 200212.
102
Transfusion Practice Evidence Based or
Behavior Based?

• Amount of transfused products was found to be
  inversely proportional to the physicians
  knowledge of transfusion indications1
• Variability in transfusion practice exists for
  coronary artery bypass surgery2,3
• Variability persists despite national consensus
  guidelines3
• Institutional variability in transfusion practice
  also exists for liver transplantation4

• Salem-Schatz SR, et al. Med Care.
  199331868-878.
• Goodnough LT, et al. JAMA. 199126586-90.
• Stover EP, et al. Anesthesiology.
  199888327-333.
• Ozier Y, et al. Anesth Analg. 200397671-679.

103
What really happens in your institution?Discuss
ion
104
Transfusion Guidelines

• Because of the risks associated with
  transfusion, physicians should remain familiar
  with currently recognized alternatives to
  transfusion. Autologous transfusion techniques
  (such as perioperative collection and
  preoperative donation) should be considered, when
  indicated, to reduce the need for allogeneic
  transfusion with its attendant risks of disease
  transmission and immune reaction