Blood Conservation talk by Dr Dafydd Thomas given at a recent Sydney Intensive Care Network meeting.

1. Blood Conservation Overview
Dafydd Thomas
Consultant in ICM
Welsh Blood Service
Chair NATA
Chair SHOT Steering Group
Past President BBTS

2. Declaration of Interests
•No conflicts
•No conflict of interest with ICS
manufacturers
•Past President BBTS
•Chair of NATA
•Chair of SHOT Steering Committee
•Seconded to Welsh Blood Service/National
Wales Informatics Service
•No current research funding/commercial
interests to declare

3. Transfusion Alternatives
• Future blood supply
– New pathogen risks
– Plentiful supply
– Ageing demographics
• Benefits of transfusion
• Adverse effects of transfusion
– TRIM, TACO, ATR etc
– Outcome better or worse
– Cost to Health Service?

4. Transfusion alternatives
Even if you wish to continue
using allogeneic blood
someone needs to cut their
use so you can continue if
supply demand is an issue

5. Transfusion alternatives?
• Other ways of treating anaemia
• Transfusion needs to become last
resort
• Integrate alternatives in main
stream practice
• Integrate in blood services
planning

7. Reducing risks of allogeneic transfusion
Donor selection
Testing
Transfusion
Transmitted
Infection
Better process
ABO
Incompatibility
Transfusion
Related ALI
TRALI
Leucodepletion
Male only plasma
Transfusion
Related
Immunomodulation
TRIM
Transfusion
Associated
Circulatory
Overload
TACO
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009, Athens-Greece

9. Attendance of WBS donors in response to
calling letters: 1990/01 – 2005/06
Donors Called
Donors Attending
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009, Athens-Greece

11. P2Y12

12. 6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

13. 6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

14. 6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

15. The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1

16. The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1

17. The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1

18. Transfusion effect ? How can we separate from surgical effect ?
Variance
Massive Haemorrhage
Complicated or Unexpected
Difficult surgery
Withhold transfusion
Minimal Haemorrhage
Complicated surgery
Straightforward Surgery
Moderate or
controlled haemorrhage
Mortality
Transfusion

21. Inter-Hospital Variability of Transfusion Rates
in Matched THR Patients
1st and 2nd Austrian Benchmark Study (n=2,570)
Transfusion rate
90%
68%
27.7% reduction in txn rate
44.1% reduction in units txed per patient
0.00% mortality
45%
23%
0%
15
Study I
Study II
12
13
16
9
3
1
7
2
11
4
6
5
8
10
Center
Gombotz H, Rehak P, Hofmann A. Blood use in elective surgery: Comparison - Austrian benchmark study I and II. Unpublished Data, 2011
Acknowledgements to Axel Hofmann & Shannon Farmer

22. The Red Cell Storage Lesion:
Structural Changes.
6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

23. 6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

24. Better planning
Pre-operative preparation
Assessing reserve
Stopping drugs
Warfarin
Aspirin
Clopidogrel
Pre-operative Association

25. Better planning
Pre-operative preparation
Assessing reserve
Stopping drugs
Warfarin
Aspirin
Clopidogrel
Starting drugs
Iron
Folate
EPO
Aprotonin
Group and Save
Pre-operative Association

26. What is Patient Blood Management ?
In MJA 1988 Professor Isbister proposed the need
for a paradigm shift in the care of patients who
are being considered for transfusion of fresh blood
products.
Originator of the term PBM
Clinical Professor James Isbister BSc(Med), MB BS, FRACP, FRCPA.
Emeritus Consultant, Haematology & Transfusion Medicine, Royal North Shore
Hospital, Sydney, Australia.
Clinical Professor of Medicine, University of Sydney, Sydney, Australia;
Adjunct Professor, University of Technology, Sydney, Sydney, Australia;
Adjunct Professor, Monash University, Melbourne, Australia;

27. How to best manage the patients own
oxygen carrying capacity…..
….to minimise dependence on the blood
bank
Author of ‘Peri-operative Blood Transfusion’

28. PBM = good clinical medicine
An approach to safe, quality patient care….
Defined as –
“the timely application of evidence-based
medical and surgical concepts designed to
maintain haemoglobin concentration,
optimise haemostasis and minimise blood loss
in an effort to improve patient outcome”,
patient blood management is expected to
reshape the future of transfusion medicine
and the way blood components are used in
clinical practice.

29. PBM = good clinical medicine
An approach to safe, quality patient care….
• Aim is to optimise, conserve and manage the
patient’s own blood to minimise or avoid
exposure to allogeneic blood
• Changing the transfusion paradigm from a
product focus to a patient focus
• Patient-specific team approach
• And results in improved patient outcomes

32. Confirms an observation by Clement Finch
decades ago that there is functional
iron deficiency …..even with
oral iron supplementation
Transferrin saturation (%)
26.0
19.5
PLACEBO
300
600
13.0
6.5
0.0
0
Basal
1
2
3
4
5
6
7
Days
Mercurali the first to show the decrease in transferrin saturation in
peri-surgical patients stimulated to donate autologous blood with EPO

33. Intravenous versus oral iron supplementation for
preoperative stimulation of hemoglobin synthesis using
recombinant human erythropoietin
Neither group required allogeneic transfusion
112 versus 110g.L-1
Blood loss 1583 ± 685 versus 1325 ± 767mls
Rohling RG, Zimmermann AP, Breymann C Journal of
Hematotherapy & Stem Cell Research. 2000;9:497-500

34. Intravenous iron and recombinant erythropoietin
for the treatment of postoperative anemia
IV iron plus EPO on day 1 and 3
IS +EPO IS
0
IS +EPO
1
5
2
3
4
6
Increase in Hb
7
Post Operative Days
Karkouti K et al Can J Anaesth 2006 Jan;53(1):11-19

35. Intravenous iron and recombinant erythropoietin for
the treatment of postoperative anemia
At six weeks increases were
37+/- 14g.L-1 40+/-7g.L-1 and 45+/- 12g.L -1
0
1
2
3
4
5
6
7
Post Operative Weeks
Karkouti K et al Can J Anaesth 2006 Jan;53(1):11-19

36. Update on adverse drug events
associated with parenteral iron
Iron sucrose
Sodium ferric gluconate
LMW iron dextran
HMW iron dextran
0.6 per million
0.9.per million
3.3 per million
11.3 per million
Chertow GM et al Nephrology Dialysis Transplantation. 2006 21(2):
378-382

37. British Journal of O&G
Online early Sept 2006

38. Lancet 2011;378:1396-407

39. Lancet 2011;378:1396-407

41. Preoperative haemoglobin assessment and optimisation template
This template1 is for patients undergoing procedures in which substantial blood loss is anticipated such as cardiac surgery, major orthopaedic, vascular and
general surgery. Specific details, including reference ranges and therapies, may need adaptation for local needs, expertise or patient groups.
Preoperative tests
• Full blood count
• Iron studies2 including ferritin
• CRP and renal function
Is the patient anaemic?
Hb <130 g/L (male) or
Hb <120 g/L (female)
NO
YES
Ferritin <30 mcg/L2,3
Ferritin 30–100 mcg/L2,3
Ferritin >100 mcg/L
CRP4
Raised
No anaemia: ferritin
<100 mcg/L
•Consider iron therapy# if
anticipated postoperative Hb
decrease is ≥30 g/L
•Determine cause and need for GI
investigations if ferritin is
suggestive of iron deficiency <30
mcg/L2,3
Iron deficiency anaemia
• Evaluate possible causes based
on clinical findings
• Discuss with gastroenterologist
regarding GI investigations and
their timing in relation to
surgery3
• Commence iron therapy#
Normal
Possible iron deficiency
• Consider clinical context
• Consider haematology advice or,
in the presence of chronic
kidney disease, renal advice
• Discuss with gastroenterologist
regarding GI investigations and
their timing in relation to
surgery3
• Commence iron therapy#
Possible anaemia of chronic
disease or inflammation, or other
cause5
• Consider clinical context
• Review renal function, MCV/MCH
and blood film
• Check B12/folate levels and
reticulocyte count
• Check liver and thyroid function
• Seek haematology advice or, in
the presence of chronic kidney
disease, renal advice

42. Pharmacological Options
• Desmopressin (DDAVP)
• Antifibrinolytics
– Epsilon aminocaproic acid
– Tranexamic acid
• Serine Protease Inhibitors
– Aprotinin
• Thrombin Generators
– rhVIIa

43. Meta-analysis of Lysine Analogues
in Heart Surgery
Control
Aspirin
1o vs Repeat
Laupacis et al Anesth Analg 1997;85:1258-1267

45. Tranexamic Acid in Knee (TKR) and
Hip (THR) Surgery
Benoni 1996
Hiippalla 1997
Jansen 1999
Hiippalla 1995
Ellis 2001
Engel 2001
Veien 2002
All TKR
Benoni 2001
Ekback 2000
Harley 2002
All THR
0.01
0.1
1
Relative Risk of Transfusion
10

46. Sunny Dzik SHOT 2011

47. Sunny Dzik SHOT 2011

48. Better planning
Pre-operative preparation
Assessing reserve
Stopping drugs
Starting drugs
Operative haemostasis
Intra-operative cell salvage
Post-operative cell salvage

50. Surgical Control of Bleeding
• Digital pressure
• Sutures and clips
• Thermal coagulation
• Topical hemostatic agents
• Organ wrapping- mesh net

51. Methods of achieving hemostasis
• Mechanical methods and devices
– Digital pressure, suture, packing, tourniquet
– Band ligation - elastic ligatures for endoscopic
ligation of esophageal varices or other blood vessels
– Hemoclips – endoscopic and laparoscopic ligation of
blood vessels
– Detachable loops – endoscopic loops / nylon, teflon/
– Intraluminal grafts and stents for aneurism repair

52. • Thermal agents – electrocautery, produce hemostasis
by heating and denaturing proteins, resulting in
coagulation
• Pharmacologic agents :
– vasoconstriction -Vasopressin, Somatostatin, epsilon-aminocaproic
acid
– Matrix for attracting blood elements
– Agents enhancing clotting factor activity –Desmopressin,
r-FVIIa .
Topical hemostatic agents should have several properties:
1) rapid hemostasis, 2) easily applied 3) hold sutures
4) little tissue reaction, 5) low infectious risk, 6) absorbable,
7) easily removed

53. Fibrinogen-based products
•
Liquid Fibrin Sealant -Tisseel® fibrinogen, factor
•
TachoComb / TachoSil®
•
•
•
•
Fibrin foam
Autologous fibrin glue
Topical thrombin
Hemostatic dressings -with Ca alginate
XII and thrombin +antifibrinolytic (aprotinin) . Sealing of bleeding
tissue starts with fibrin formation, the end stages of natural
blood coagulation. Fibrinogen is converted to fibrin strands that
join into net-like matrices
and aprotonin on collagen mesh
- dry fibrinogen, thrombin

54. Collagen-based products
• Avitene®
(Alcon,Inc.)
• Floseal®
(Baxter)
Microfibrillar collagen hemostat Effective
in controlling arterial bleeding. Can be used on irregular surfaces.
Easy removal with irrigation and suction reduces rebleeding and the
need for multiple applications.
Gelatin matrix of collagen and topical
human thrombin. Works on wet, actively bleeding tissue, can be
applied focally or extruded and spread to cover a large area of
diffuse bleeding

55. Oxidized Regenerated Cellulose
•
For control of capillary, venous and arterial bleeding in
cases when conventional methods for hemostasis are
ineffective.
SURGICEL®
•
•
•
•
•
Fast resorption (1-2 weeks)
Minimal tissue reaction
No allergenic reaction
Easy to apply
Antibacterial properties!
ARISTA ® (Ethicon,Inc.)
absorbable hemostat, based on microporous
polysaccharide hemospheres. Used in the
control of profuse bleeding. The particles act
as a molecular filter producing “instant gelling”,
followed by the formation of a fibrin mesh

56. Nonsurgical Interventions
to Achieve Hemostasis
• Pneumatic antishock garment
• patients with pelvic and lower extremity
fractures
• hypovolemic shock
• Angiographic embolization
• Temporary balloon occlusion

57. External pelvic
fixator –
fractures associated
with a diastasis of the
pubic symphysis (“openbook” pelvic fractures)

58. Some things don’t change
• It still rains in Wales
• There are still instances when blood
components are given without good reason
or are wasted
• More instances of wastage than of failure to
provide
• Big difference between withholding a
transfusion on clinical grounds and not
transfusing when indicated.

59. 12 November 2012

60. 26 November 2012

61. Cell salvage in emergency bleeding
•
•
•
•
Life saving provision of autologous blood
May be the only available blood
Warm, active O2 carriage High 2,3 DPG
Decreases demand on allogeneic supplies
6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

62. Grade IV Liver trauma
6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

63. Intra-operative Blood
Requirements
60
Units
45
Allogeneic
Autologous Blood
30
15
0
16F
31M
23M
19M
6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

64. 6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece

65. MSBOS & Cell Saved Units
Operation 1993
THR
2-3
Rev THR
4-6
TKR
2-3
AAA
6-8
Fem-Popliteal 2
Aorto-Bifem 4
Cystectomy 6
Nephrectomy 4
Mean
<1
2-3
1.5
3
<1
<1
2-3
2
6th Seminar of the Hellenic Blood
Transfusion Society-March 13-14, 2009,
Athens-Greece
2001
G+S
2
G+S
3
G+S
G+S
2(^3)
2

66. Early coagulopathy in multiple injury: an analysis from
the German Trauma Registry on 8724 patients
90
68
ISS 1-15
ISS 16-24
ISS 25-49
ISS 50-75
45
23
0
<1000
1000+
2000+
3000+
4000+
0C

67. 3
2.5
2
1.5
1
0.5
pH
0
Relative Rate of FVIIa Generation
Meng ZH et al J Trauma 2003;55:886-891
6.2 6.6 7
7.4 7.8 8.2 8.6 9
Inhibition of 70% at pH 7.0 as compared to 7.4

68. Wolberg et al J Trauma 2004;56(6):1221-1228
• Bleeding observed at mildly reduced
temperatures (330C-370C) results primarily
from a platelet adhesion defect and not
reduced enzyme activity or platelet activation
• At temperatures below 330C both reduced
platelet function and enzyme activity likely to
contribute to the coagulopathy

71. Tissue Oxygen partial pressure, mmHg
Organ Specific PO2 During a Wide Range of Hcts
70
60
50
40
30
20
10
0
Cardiac output, %
180
150
120
100
0
42
30
25
19
Arterial hematocrit, %
Skeletal muscle
Liver
Pancreas
Small instestine
Kidney
Messmer K, et al. Res Exp Med (Berl) 1973;159:152-166

73. O2 – consumption (VO2)
!T
iss
ue
Hy
po
xia
!
Limit of Hemodilution
„critical“ DO2
O2 – delivery (DO2)

75. Transfusion requirements in critical care
(TRICC): a multicentre, randomised, controlled
clinical study
• 30 day mortality similar in both groups
Apache <20 23% P=0.11)16.1% P0.03)
(8.7% v
(18.7% v’s
< 50yrs 5.7%(8.7% v’s 16.1% P0.03)
• Apache <20 v 13% P 0.02%)
• < 50yrs 5.7% v’s 13% P 0.02%)
• Significant cardiac disease 20.5% v’s
22.9%
Paul C Hébert et al NEJM 1999 No6 Vol 340 p409-17

76. Transfusion triggers: have we gone too low?
Transfusion Requirements
in Orthopedic Surgery (TRIOS)
Élise Vuille-Lessard, B.Sc.
Monique Ruel, R.N.
Jean-François Hardy, M.D.
Department of Anesthesiology
CHUM Notre-Dame
Montreal, Canada
NATA Annual Symposium
Dublin, 7-8 April 2011

83. Newest –Great Data from Virginia
Study is being widely heralded!

84. Tx Reduction Improved Outcomes!
This program saved the state of Virginia $49,000,000.00

88. Diolch