Dafydd Thomas on Blood Conservation

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