Transcript Slide 1

Transfusion Medicine Residency Program
Cases and Chapters
Blood Conservation
Dr. D.K. Towns
June 18, 2009
Outline
1. Guideline Driven Blood Product Use
2. Pharmaceutical Preparations
a) Desmopressin (DDAVP)
b) Anti-fibrinolytics
i) Aprotinin
ii) Lysine analogues (Tranexamic acid, e-Aminocaproic acid)
c) Recombinant Factor FVIIa (rFVIIa)
d) Topical hemostatic agents ex. fibrin sealant
e) Erythropoietin (EPO)
f) Iron
g) Anticoagulation reversal
Outline (continued)
3. Autologous
a) Pre-operative deposit
b) Cell salvage
i) intraoperative
ii) postoperative
c) Acute Normovolemic Hemodilution
4. Multi-Disciplinary Approach to Blood Management
a) Preoperative
b) Intraoperative
i) Surgical
ii) Anesthetic
c) Postoperative
Outline (continued)
6. Blood "Substitutes"
a) Perfluorochemicals
b) Hemoglobin based oxygen carriers (HBOC's)
c) Liposome-encapsulated hemoglobin
7. Case presentations
1. Guideline Driven Blood Product
Use
• Creating transfusion criteria decreases the
likelihood of transfusion
• Should be created by a multidisciplinary team
based on evidence
• Evidence is key
• Audit before and after implementation
2. Pharmaceutical Preparations
a) Desmopression (DDAVP)
- increases circulating levels of FVIII and VWF
- a Cochrane review of adult elective surgery without bleeding
disorders concluded that it doesn't decrease RBC loss, risk of
allogeneic transfusion, volume of RBC transfused, or mortality
- it is associated with 2-4 x increased risk of myocardial infarction
in cardiac surgery patients
- bottom line - its use should be restricted to the management of
patients with Hemophilia A and von Willebrand's Disease
b) Antifibrinolytics
i) Aprotinin
- direct inhibitor of plasmin (a fibrinolytic enzyme)
- anaphylaxis possible, especially with repeat doses
- decreases the need for allogeneic blood transfusion, bleeding,
and re-exploration in cardiac surgery
- not extensively studied in non-cardiac surgery
- several meta-analyses have shown favourable outcomes in
reducing mortality, risk of stroke, and need for repeat surgery in
massive bleeding
- observational study in 2007 (Mangano, NEJM) reported that
aprotinin use was associated with 2x risk of renal failure in
cardiac surgery, and, 55% increase in the risk of MI or heart
failure, and 181% increase in the risk of stroke or encephalopathy
ii) Lysine analogues - Tranexamic acid Cyklokapron (+ e-Aminocaproic acid - Amicar)
- bind to plasminogen and inhibit its finding to
fibrin, thus impairing fibrinolysis
- appear to show less safety concerns but
contraindicated if patient is at risk of
thrombosis
- fewer randomized trials than with Aprotinin
cheaper than Aprotinin
Brown et al (Circulation 2007) published a meta-analysis of
randomized trials which confirmed the effectiveness in
decreasing blood loss and transfusion, but suggested no
significant risks or benefits for mortality, stroke, MI; (it did
suggest an association of aprotinin and risk of renal dysfunction)
• Most recently, the Blood Conservation using Antifibrinolytics in
a Randomized Trial Investigators (Fergusson, Hebert, Mazer NEJM 2008) published the findings of their multi-centre RCT
of aprotinin and lysibne analogues in high risk cardiac surgery
• The study was terminated because of a strong and consistent
negative mortality trend associated with aprotinin as
compared with lysine analogues
• November, 2007 Bayer and Nordic Pharma suspended global
marketing of aprotinin
c) Recombinant factor VIIa
• Binds to tissue factor at the site of tissue injury
and vascular wall disruption, generating
thrombin and activating platelets
• rFVIIa acts on the platelet surface, which
generates a thrombin burst, leading to the
conversion of fibrinogen to fibrin
• As well, rFVIIa results in clot stabilization by
inhibition of fibrinolysis
• Major indication is perioperative prophylaxis and treatment of
bleeding episodes in hemophiliac patients with inhibitors against
factors VIII and IX, and for patients with acquired hemophilia,
coagulation VII deficiency, and Glanzmann's thrombasthenia
• “Off-label" use has increased in patients with severe acquired
coagulopathy and uncontrollable nonsurgical bleeding associated
with surgery and trauma
• Concerns about intravascular thrombosis leading to increased
morbidity and mortality
• A recent systematic review (Ranucci et al, Arch Surg 2008) found
that it was effective in decreasing blood transfusion (in major blood
loss surgery) with no major safety concerns
• Awaiting publication of recent RCT's
• It is expensive
d)
Topical Hemostatic agents - ex.
fibrin sealant (Tisseel)
• Fibrin sealant - combination of thrombin
and fibrinogen mixed with calcium to form
fibrin
• commercially available, or, can be
produced from autologous plasma
e) Erythropoietin
•
Primary regulator of the production of RBC's by stimulating erythryopoiesis
with hypoxia being its major stimulus
•
Used to replenish RBC volume in patients undergoing preop autologous
donation, or in patients with refractory anemia
•
Effect is rapid (2-3 days)
•
Equivalent of one unit of blood is seen in 7 days, although 2-4 weeks is
necessary for adequate erythropoiesis to occur
•
Adverse events include thrombotic events, hypertension, seizures, and rare
cases of red cell aplasia
•
Patients benefited the most had a hemoglobin below 13.5 g/dL
•
Iron supplementation maximizes its benefit
•
Used in combination with other blood conservation strategies
f) Iron
• Iron deficiency anemia should ideally be
corrected prior to elective surgery
• Iron therapy is not beneficial in non-iron
deficient patients without corresponding
use of EPO
g) Anticoagulation reversal
• Patient factors should be taken into considered when discontinuing,
or modifying anticoagulation
• Warfarin - Vitamin K
• (Octaplex in setting of blood conservation, if emergency surgery)
• Heparin - Protamine
• ASA - discontinue 2 days prior to surgery (7 days preferable)
• Plavix - discontinue 5 days prior to surgery (7 days preferable)
• Other NSAIDS - discontinue "5 half-lives" prior to surgery
3. Autologous
i) Pre-operative deposit
• Not for all surgeries - should have at least a 10% chance of requiring
blood
• Not all patients are eligible
• Optimal timing is 21 - 34 days prior to surgery, 1 week apart,
therefore maximum 3-4 units
• ? epo/iron
• 50% wastage rate; usage markedly declining in Canada, and
worldwide
• Reduction in likelihood of allogeneic transfusion, but increased
likelihood of any transfusion
ii) Cell Salvage
• Usually contraindicated if risk that blood may be
contaminated (infection, tumour, topical
disinfectants)
• Induce some degree of mechanical injury to the
red cells
• Intra-operative
– cardiac surgery has largest average number of units
recovered
Two types of devices:
– Simpler, less expensive, canister type - blood is anti-coagulated
and aspirated using a vacuum supply into a disposable liner bag
with a filter
– Blood can be concentrated and washed in the blood bank or
directly re-infused
– Potential for inflammatory "soup" + particulate matter to be
transfused - although few untoward consequences (?coagulion
abnormalities)
– Not useful for large volumes
Automated
- Centrifuge assisted semi-continuous flow; requires technical
expertise;
- Anticoagulates, washes, and concentrates the red cells before
re-infusion
Postoperative
- Several devices are available
- Red cells should be washed prior to re-infusion and infused
through a microaggregate filter within 6 hr of starting the
procedure
iii) Acute Normovolemic Hemodilution
• Removal of whole blood from the patient immediately before surgery
along with simultaneously of crystalloid or colloid
• Collected in standard blood bags containing citrate anticoagulant
• Target hematocrit is about .25 - .30
V = EBC x initial Hct - desired Hct
average Hct
• Rationale - blood loss occurs at a lower hematocrit
• Contraindications - significant coronary, pulmonary, renal, or liver
disease, infection
• Efficacy is dubious
CSA Standards Z902-04 Blood and Blood
Components
12.5 Perioperative collection (pages 57, 58)
(includes intraoperative + postoperative cell
salvage and ANH)
"The blood centre or transfusion service
should be involved in the development of the
policies and procedures used in the
management of the perioperative blood
recovery program."
4. Multi-disciplinary Approach
Pre-op
- maximize patient's hemoglobin
- correct impaired hemostasis
- nutritional status
Intra-op
- Anesthetic
• controlled hypotension (minimal benefit shown; risk of end organ ischemia)
• regional anesthetic techniques
• normothermia (?benefit)
- Surgical
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careful ligation of blood vessels, and other "good surgical technique"
laparascopic techniques
optimize cautery
topical thrombogenic agents as appropriate
Post-op
- minimize blood draw - worst in ICU, and with arterial line in place
5. Blood Substitutes
Red Cell Substitutes
- usually refer to oxygen carrying solutions
that can both expand the blood volume and
oxygenate tissues
Wish list for "ideal" substitute is long …
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small molecule
delivers O2 efficiently
universal compatibility
sterilized
no risk of disease transmission
no immunosuppressive effects, or interaction with the immune system
maintenance of arterial blood pressure and pH
abundant supply
long shelf-life at room temp
reconstitutes easily
cost-effective
no toxicity
ease of administration
no interference with capillary circulation
ability to access all areas of the body including ischemic tissue
in vivo half-life similar to the red blood cell
rapid metabolization and elimination in vivo
3 general classes
1) Perfluorochemicals
2) Hemoglobin-based oxygen carriers (HBOC's)
3) Liposome encapsulated hemoglobin
6. Case Presentations
Case #1
14 year old female, 50 kg, otherwise healthy, for
anterior/posterior correction of idiopathic scoliosis.
What intra-operative modalities would you
consider to decrease transfusion?
What postoperative therapies would you consider?
Case #2
84 year old woman for revision hip arthroplasty, seen preop for Hb 100.
•
How would you investigate this patient’s anemia?
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How would you treat? What is your target?
•
(Assuming iron deficiency, or mixed iron deficiency/ACD):
– Oral iron: How much? What kind? How long to effect? How
do you deal with side effects?
– IV iron: Who’s a candidate? How much? How often? How
long to effect?
•
EPO? Who’s a candidate? How much? How often? What do you
tell patients about the potential for adverse effects?
Case #3
Jehovah’s Witness patient for bilateral total knee
arthroplasty. Management?
• Assume we’ve decided to do just one knee – How does
management of this patient differ from others?
• An opportunity to discuss accepted vs. unaccepted
modalities in these patients.
Case #4
Or (one of our recent cases here): JW waiting to
have primary knee arthroplasty done, sprouted a
GI bleed and was admitted to hospital with Hb 56.
• How do you treat this patient?
• Essentially it was an epo/iv fe resuscitation – I
could probably scare up more details on this
case if you like.
Case #5
Obstetrics! We recently had a case of a pregnant woman
with an Anti-InB (high-incidence antigen) – no risk to baby
but potential risk of hemolytic reaction if antigen positive
blood transfused.
• Management?
• No family members who were In-B negative. One unit of
autologous blood donated – I can’t remember when in
the pregnancy it was donated, but it was definitely
frozen. So maybe combine this case with something like
a placenta previa – then discuss autologous in
pregnancy and issues of timing, as well as the use of cell
saver during c-section.
Case #6
67 year old male, JW. Admitted to ER with
rectal bleeding. CBC shows Hgb 57, WBC
0.7 and plt 9. Bone marrow aspirate and
biopsy consistent with aplastic anemia.