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Blood Conservation talk by Dr Dafydd Thomas given at a recent Sydney Intensive Care Network meeting.
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Dafydd Thomas Consultant in ICM
Welsh Blood Service Chair NATA
Chair SHOT Steering Group Past President BBTS
Blood Conservation Overview
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
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?
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
Transfusion alternatives?
• Other ways of treating anaemia • Transfusion needs to become last
resort • Integrate alternatives in main
stream practice • Integrate in blood services
planning
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009, Athens-Greece
Transfusion Transmitted
Infection
ABO Incompatibility
Transfusion Related ALI
TRALI
Transfusion Associated Circulatory Overload
TACO
Transfusion Related
Immunomodulation TRIM
Donor selection Testing
Better process
Male only plasma
Leucodepletion
Reducing risks of allogeneic transfusion
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009, Athens-Greece
Attendance of WBS donors in response to calling letters: 1990/01 – 2005/06
Donors Called Donors Attending
P2Y12
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1
The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1
The Journal of Thoracic and
Cardiovascular Surgery Volume 142,
Number 2 249.e1
Massive Haemorrhage
Complicated or Unexpected Difficult surgery
Withhold transfusion Complicated surgery
Moderate or controlled haemorrhage
Minimal Haemorrhage
Straightforward Surgery
Mortality
Transfusion
Transfusion effect ? How can we separate from surgical effect ?
Variance
Inter-Hospital Variability of Transfusion Rates in Matched THR Patients
1st and 2nd Austrian Benchmark Study (n=2,570)
0%
23%
45%
68%
90%
15 12 13 16 9 3 1 7 2 11 4 6 5 8 10
Center
Tran
sfus
ion
rate
Study IStudy II
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
27.7% reduction in txn rate 44.1% reduction in units txed per patient 0.00% mortality
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
The Red Cell Storage Lesion: Structural Changes.
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
Better planning Pre-operative preparation Assessing reserve Stopping drugs Warfarin Aspirin Clopidogrel
Pre-operative Association
Better planning Pre-operative preparation Assessing reserve Stopping drugs Warfarin Aspirin Clopidogrel Starting drugs Iron Folate EPO Aprotonin Group and Save
Pre-operative Association
What is Patient Blood Management ?
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;
Originator of the term PBM
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.
Author of ‘Peri-operative Blood Transfusion’
How to best manage the patients own oxygen carrying capacity….. ….to minimise dependence on the blood bank
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.
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
PBM = good clinical medicine An approach to safe, quality patient care….
Mercurali the first to show the decrease in transferrin saturation in peri-surgical patients stimulated to donate autologous blood with EPO
0.0
6.5
13.0
19.5
26.0
0 1 2 3 4 5 6 7
PLACEBO300600
Tran
sfer
rin
satu
rati
on (
%)
DaysBasal
Confirms an observation by Clement Finch decades ago that there is functional
iron deficiency …..even with oral iron supplementation
Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using
recombinant human erythropoietin
Rohling RG, Zimmermann AP, Breymann C Journal of Hematotherapy & Stem Cell Research. 2000;9:497-500
Neither group required allogeneic transfusion 112 versus 110g.L-1
Blood loss 1583 ± 685 versus 1325 ± 767mls
Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia
Karkouti K et al Can J Anaesth 2006 Jan;53(1):11-19
Post Operative Days
0 1 2 3 4 5 6 7
IS +EPO IS +EPOIS Increase in Hb
IV iron plus EPO on day 1 and 3
Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia
Karkouti K et al Can J Anaesth 2006 Jan;53(1):11-19
Post Operative Weeks
0 1 2 3 4 5 6 7
At six weeks increases were 37+/- 14g.L-1 40+/-7g.L-1 and 45+/- 12g.L -1
Update on adverse drug events associated with parenteral iron
Chertow GM et al Nephrology Dialysis Transplantation. 2006 21(2):378-382
Iron sucrose 0.6 per million Sodium ferric gluconate 0.9.per million LMW iron dextran 3.3 per million HMW iron dextran 11.3 per million
British Journal of O&G Online early Sept 2006
Lancet 2011;378:1396-407
Lancet 2011;378:1396-407
Is the patient anaemic? Hb <130 g/L (male) or Hb <120 g/L (female)
Preoperative tests • Full blood count
• Iron studies2 including ferritin • CRP and renal function
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.
Ferritin <30 mcg/L2,3
NO YES
Ferritin >100 mcg/L
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
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#
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#
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
Raised Normal
CRP4
Ferritin 30–100 mcg/L2,3
Pharmacological Options• Desmopressin (DDAVP)
• Antifibrinolytics – Epsilon aminocaproic acid – Tranexamic acid
• Serine Protease Inhibitors – Aprotinin
• Thrombin Generators – rhVIIa
Meta-analysis of Lysine Analogues in Heart Surgery
ControlAspirin
1o vs Repeat
Laupacis et al Anesth Analg 1997;85:1258-1267
Tranexamic Acid in Knee (TKR) and Hip (THR) Surgery
0.01 0.1 1 10All THR
Harley 2002Ekback 2000Benoni 2001
All TKRVeien 2002Engel 2001
Ellis 2001Hiippalla 1995
Jansen 1999Hiippalla 1997
Benoni 1996
Relative Risk of Transfusion
Sunny Dzik SHOT 2011
Sunny Dzik SHOT 2011
Better planning Pre-operative preparation Assessing reserve Stopping drugs Starting drugs Operative haemostasis Intra-operative cell salvage Post-operative cell salvage
Surgical Control of Bleeding
• Digital pressure • Sutures and clips • Thermal coagulation • Topical hemostatic agents • Organ wrapping- mesh net
• 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
Methods of achieving hemostasis
• 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
Fibrinogen-based products • Liquid Fibrin Sealant -Tisseel® fibrinogen, factor
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
• TachoComb / TachoSil® - dry fibrinogen, thrombin and aprotonin on collagen mesh
• Fibrin foam • Autologous fibrin glue • Topical thrombin
• Hemostatic dressings -with Ca alginate
Collagen-based products • Avitene® (Alcon,Inc.) 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.
• Floseal® (Baxter) 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
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
Nonsurgical Interventionsto Achieve Hemostasis
• Pneumatic antishock garment • patients with pelvic and lower extremity
fractures • hypovolemic shock • Angiographic embolization • Temporary balloon occlusion
External pelvic fixator –
fractures associated with a diastasis of the pubic symphysis (“open- book” pelvic fractures)
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.
12 November 2012
26 November 2012
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
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
Grade IV Liver trauma
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
Intra-operative Blood RequirementsU
nits
0
15
30
45
60
16F 31M 23M 19M
AllogeneicAutologous Blood
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
6th Seminar of the Hellenic Blood Transfusion Society-March 13-14, 2009,
Athens-Greece
Operation 1993 Mean 2001 THR 2-3 < 1 G+S Rev THR 4-6 2-3 2 TKR 2-3 1.5 G+S AAA 6-8 3 3 Fem-Popliteal 2 < 1 G+S Aorto-Bifem 4 < 1 G+S Cystectomy 6 2-3 2(^3) Nephrectomy 4 2 2
MSBOS & Cell Saved Units
Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients
0
23
45
68
90
<1000 1000+ 2000+ 3000+ 4000+
ISS 1-15ISS 16-24ISS 25-49ISS 50-75
0C
Meng ZH et al J Trauma 2003;55:886-891
pHRel
ativ
e R
ate
of F
VIIa
Gen
erat
ion
Inhibition of 70% at pH 7.0 as compared to 7.4
6.2 6.6 7 7.4 7.8 8.2 8.6 9
0 0.
5 1
1.5
2 2.
5 3
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
Organ Specific PO2 During a Wide Range of Hcts
Messmer K, et al. Res Exp Med (Berl) 1973;159:152-166
Tissu
e Oxy
gen p
artia
l pre
ssur
e, mm
Hg
Skeletal muscle
Card
iac ou
tput, %
Liver Pancreas Small instestine Kidney
42 30 25 19
70
60
40
30
20
10
0
50
180
150
120
0100
Arterial hematocrit, %
„critical“ DO2
O2 – delivery (DO2)
O2 –
con
sum
ptio
n (V
O2)
Limit of Hemodilution! T
issue
Hyp
oxia
!
Transfusion requirements in critical care (TRICC): a multicentre, randomised, controlled
clinical study
• 30 day mortality similar in both groups (18.7% v’s 23% P=0.11)
• Apache <20 (8.7% v’s 16.1% P0.03) • < 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
Apache <20 (8.7% v 16.1% P0.03) < 50yrs 5.7% v 13% P 0.02%)
Transfusion Requirementsin 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
Transfusion triggers: have we gone too low?
Newest –Great Data from Virginia
Study is being widely heralded!
Tx Reduction Improved Outcomes!
This program saved the state of Virginia $49,000,000.00
Diolch