PBM. Preoperative Anemia Management, Dr García Erce. Roma 2015

Title
Dr.
“PATIENT BLOOD MANAGEMENT:
Strategies and protocols to optimize
hemoglobin levels”
Dr José Antonio García Erce

POSTGRADO UNIVERSITARIO EN BLOOD
ConflictsExternal Assesor
- AMGEN Oncología 2010/2012
- Roche Anemia 2009
- Ditassa-Ferrer 2004
Speach/Talks, investigations trials, grants, collaborations
-Vifor-Uriach/Ferralinze
-Janssen-Cilag/Braun
-Astra-Tech de Aztra Zeneca/Well-Health?/GSK
-Sanofi Aventis/Esteve/Novartis/Octapharma
-Cobe-Caridian/Roche Oncología/AMGEN Oncologia
Member CAT 2002-2005
Member Documento de Sevilla “Alternativas a la Transfusión”
Member Documento LatinoAmericano de la Anemia
Member GIEMSA/AWGE/SETS/AEHH/NATA
Scientific Committe NATA
SEHH representative in ONT (Organización Nacional de Transplante)
Coordinator of Working Group “Hemoterapia con sentido común”

Acknowledgements
Prof. Manolo Muñoz Gómez
GIEMSA. Transfusion Medicine. Facultad de Medicina
Universidad de Málaga
Dr. Jorge Cuenca Espiérrez
Department of Orthopaedic Surgery. University Hospital Miguel Servet, Zaragoza
Prof. Antonio Herrera Rodríguez
Cátedra Department of Orthopaedic Surgery. University Hospita Miguel Servet,
Zaragoza
Dra. Elvira Bisbe
Department of Anaesthesiology. University Hospital Mar-Esperança, Barcelona
Dr Manuel Quintana Díaz
Servicio de Urgencias de Adultos. Hospital Universitario La Paz. Madrid

ANAEMIA Y PATIENT BLOOD MANAGEMENT
WHY?

Incidence of perioperative anaemia (& iron deficiency)

25%
Incidence/Prevalence of anaemia

ortesy/Modificated from Prof M Muñoz. / Kassebaum NJ et al. Blood 2014; 123: 615-624
Data from 187 countries (1990 – 2010)
1990 2010
HombresMujeres
1990 2010
Prevalence(x100.000habitants)
50
40
30
20
10
BLEEDING
Malaria
Anquilostoma
Esquistosoma
HbS/ falciform A
Talasemias
CKD Diabetes
CKD HipertensiOn
Another CKDs
IRON DEFICIT
Incidence/Prevalence and etiology of anaemia

POSTGRADO UNIVERSITARIO EN BLOODCortestía/Modifiicada Prof. M. Muñoz
Incidence of perioperative anaemia
Shander et al. 2004

Wen-Chih Wu et al. JAMA 2007; 297: 2481 – 2488
Haematocrit < 39%
Procedure Patients (n) n %
General surgery 106 340 45 478 42.8
Urology 59 157 21 408 36.2
Orthopaedics 57 636 25 131 43.6
Periferic vascular 47 734 24 865 52.1
Thoracic 14 051 6 780 48.3
Others 25 393 9 308 36.7
Overall 310 311 132 970 42.8
Cortestía/Modifiicada Prof. M. Muñoz
Preoperative Anaemia

Anaemia* Patients
N (%)
Mortality
OR (CI 95%)
Morbildity**
OR (CI 95%)
No-anaemics 158196 (69.4) 1 1
Anaemics 69229 (30.4) 1.42 (1.31 – 1.54) 1.35 (1.30 – 1.40)
• Slight 57870 (25.4) 1.41 (1.30 – 1.53) 1.31 (1.26 – 1.36)
• Moderate - severe 11359 (5.0) 1.44 (1.29 – 1.60) 1.56 (1.47 – 1.66)
Total: 227425 patientes
* Slight anaemia: Hto >29% – <36/39%; Moderated-severe anaemia: Hto ≤29%.
** One o more cardiac, respiratory, renal, neurologic or surgical wound complications,
sepsis or deep venous thrombosis (30d postOP).
© Prof. M. Muñoz

130 patients colon-rectal cáncer (period 12-months)
• 41% déficit de hierro con anemia (53/130) (Hb <11.5 – 12.5 g/dL)
• 60% déficit de hierro (77/130) (Ferritina <15 ng/L ± TSI <14%)
Beale et al. Colorectal Disease 2005; 7: 398-402
358 patients with colon-rectal cancer
• 23% anaemia (82/358) (Hb <10 g/dL)
• 40% iron deficit (70/173) (Fe <40 mg/dL)
Sadahiro et al. J Gastroenterol 1998; 33: 488-94
63 patients colon-rectal cancer
• 70% anaemia (Hb <12 – 14 g/dL)
• 80% low serum iron (Fe <12.5 – 14.3 mmol/L)
• 40% low ferritin (<20 ng/L) or low MCH (< 27 pg)
Prutki et al. Cancer Lett. 2006;238:188-96.
“Anaemia in colon cancer surgery”
Muñoz M, Campos A, García-Erce JA.
Intravenous iron in colorectal cancer surgery.
Seminars in Hematology 2006; 43, S36-S38

Anemia: 18 %
“Anaemia in Orthopaedic Surgery” Muñoz M et al. Blood Transfus.
2012;10(1):8-22

Risks of preoperative anaemia
“Transfusional”

Hb 130-140 g/l
100
75
62
46
25
0 20 40 60 80 100
%TRANSFUSION
Hb < 110 g/l Hb 110-120 g/l Hb 120-130 g/l
Hb > 140 g/l
García Erce JA, et al. FACTORES PREDICTIVOS DE LA NECESIDAD DE TRANSFUSION EN LA FRACTURA
SUBCAPITAL DE CADERA EN PACIENTES DE MÁS DE 65 AÑOS. Med Clin (Barc) 2003;120(5):161-6.
Haemoglobin level and Transfusional Risk

Rosencher et al. OSTHEO study. Transfusion 2003.
Transfusionprobability(%)
Women
Men
1680 THA, TKA
↑10% ABT per ↓1 g/dL Hb
Haemoglobin (g/dL)
8 9 10 11 12 13 14 15 16
31.2%
Patients(%)
Haemoglobin (g/dL)
© Prof. M. Muñoz- Modified/Cortesy Prof Muñoz

“Morbility and Mortality”

Aumentodelriesgo
© Prof. M. Muñoz- Modified/Cortesy Prof Muñoz

Anaemia OR ajusted [CI 95%] p
Allogenic Transfusion 4.7 [3.8 – 5.8] <0.001
Hospital stay >5 days 2.5 [1.9 – 3.4] <0.001
Readmission 90 days 1.4 [1.1 – 1.9] <0.005
5165 knee and hip arthroplasties
6 fast-track danish centers (January 2010 – December 2011)
662 anaemics (13%) (OMS criteria)

Risks of Allogeneic Blood Transfusion

Muñoz et al, Med Clin 2007
Shander, Farmer y Hoffman, Oncologist 2011
 “Adverse effects”
 “Clerical errors” (Wrong blood/patient)
 Viral and bacterial transmission
 Inmunological complications (TRALI, TRIM)
 Circulatory overload (TACO)
 Costs are increasingly rising (≈ 400 €/ RBC unit transfused)
 Limited resource (Aging population)
 Transitory measure (Efficacy?)
 Legal and ethical issues (Beneficience and Patient´s Authonomy
Allogeneic transfusion concerns
© Prof. M. Muñoz. Cortesy Prof Muñoz

The findings of the 1998 meta-analysis were confirmed, with small variations in some
estimates. Identification of 237 references. Thirty-six studies on 12,127 patients were
included: 23 showed a detrimental effect of PBT; 22 used also multivariable analyses,
and 14 found PBT to be an independent prognostic factor.
Pooled estimates of PBT effect on colorectal cancer recurrence yielded overall OR of
1.42 (95% CI, 1.20 -1.67) against transfused patients in randomized controlled studies.
Stratified meta-analyses confirmed these findings, also when stratifying
patients by site and stage of disease. The PBT effect was observed regardless of
timing, type, and in a dose-related fashion, although heterogeneity was
detected. Data on surgical techniques was not available for further analysis.

Eighteen studies (9120 GC patients) were included, of which 36.3% received transfusions.
ABT was associated with increased all-cause mortality (OR, 2.17; 95% confidence interval
[CI], 1.72-2.74; p < 0.001).
Dose response meta-analysis revealed that all-cause mortality was significantly lower in
patients transfused with 800 mL of blood than those transfused with >800 mL (OR, 0.58;
95% CI, 0.37e0.92; p ¼ 0.02; I2 ¼ 54%). ABT was also associated with increased cancer-
related mortality (OR, 2.57, p ¼ 0.011) and recurrence (OR, 1.52, p ¼ 0.017).
Conclusions: In GC patients undergoing curative surgeries, ABTs are associated
with a worse prognosis, including all-cause mortality, cancer-related mortality and
recurrence. PATIENT BLOOD MANAGEMENT should be investigated further to
minimize use of ABT.

Management of Blood Transfusion

The outcome, optimal use of blood is defined as:
The safe, clinically effective and efficient use of
donated human blood
€ 2010
Safe: No adverse reactions or infections
Clinically effective: Benefits the patient
Efficient: No unnecessary transfusions.
Transfusion at the time the patient needs it

It is necessary to reduce the unnecessary transfusions. This
can be achieved through the appropriate clinical use of blood,
avoiding the needs for transfusion and use of alternatives to
transfusion.
The commitment of the health authorities, health care providers
and clinicians are important in prevention, early diagnosis
and treatment of diseases/ conditions that could lead to the
need for blood transfusion.
http://www.who.int/bloodsafety/clinical_use/en/
Blood transfusion is an essential part of modern health care. Used
correctly, it can save life and improve health. However, as with
any therapeutic intervention, it may result in acute or delayed
complications and carries the risk of transmission of infectious
agents.
WHA 63.12 (resolution). Availability, safety and quality of blood products,
2010.
Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf.

WHY?
HOW?

Risks of preoperative Anaemia
ANAEMIA & PATIENT BLOOD MANAGEMENT
Incidence of preoperative Anaemia
Management of preoperative Anaemia
Management of Blood Transfusion

TREATMENT OF THE PRESURGICAL ANAEMIA
Hypoxia
Oxygen Debt
Treatment/
Management
Illness/diseases
ANAEMIA
Substitutes?
Transfusional
Haemoglobin
level?
Farmacological
NO, THANK YOU!

ANAEMIA
and
“PATIENT BLOOD MANAGEMENT”

ANAEMIA & “PATIENT BLOOD MANAGEMENT”
Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013
update of the "Seville Document“. Blood Transfus. 2013 Jun 17:1-25.

Autologous Blood
• Donation preoperative
• Hemodilution
• Recovery perioperative (Cell Saver)
Transfusional
“restrictive” ciriteria
Hb <70-80 g/L
Bleeding
reduction
• Aprotinin ?
• Antifibrinolitics
• Desmopresin
• Fibrinogen
• Prothrombin Complex
• rFVIIa ?
Erythropoiesis
Stimulation
• B12 Vitamin
• Folic Acid
• rHuEpo
• IRON
ALTERNATIVES
TO ALLOGENEIC
BLOOD
TRANSFUSION
Spaniard
PBM
Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013
update of the "Seville Document“. Blood Transfus. 2013 Jun 17:1-25.© Prof. M. Muñoz. Cortesy Prof Muñoz

WHA 63.12 (resolution). Availability, safety and quality of blood products,
2010.
Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf.
Perioperative
optimization of
haematopoiesis
Minimization of
blood loss and
perioperative
coagulopathy
Optimize
tolerance to
postoperative
anaemia
Health-care services of member states should establish
multidisciplinary, multimodal perioperative
Patient Blood Management programs, based on:
© Prof. M. Muñoz

Preoperative

Preoperatorio

"Whenever clinically feasible, patients undergoing elective
surgery with a high risk of severe postoperative anaemia
should have their haemoglobin level and iron status tested,
preferably at least 28 days before the surgical procedure.
For patients >60 years old, B12 vitamin and folic acid should
also be measured".

 Detection of anaemia, preferably at least 28 days before
the surgical procedure.
 Classification of anaemia to implement appropriate
treatment, if possible.
 Unexplained anaemia should be further investigated and
surgical procedure postponed, if possible.
 Haematinic defficiencies without anaemia should be
supplemented to allow:
• Preoperative Hb optimization.
• Hastening the recovery from postoperative anaemia.
Goodnough et al. NATA guidelines. BJA 2011;106:13-22.
Seville Document Update. Blood Transfusion 2013.
The "ORTHODOX " approach
How can we manage preoperative anaemia?
© Prof. M. Muñoz/Cortesy Prfo Muñoz

Low preOP Hb levels ≈ 150 mg of iron to increase Hb 1 g/dL
Low/empty iron stores 20-25 ng/mL of ferritin to increase Hb 1 g/dL: 100
ng/mL to recover from 3-4 g/dL Hb loss
Inflammation Hepcidin impairs/blocks iron absorption from intestine
and iron mobilisation from macrophages
Surgical blood loss 500 mL of blood contain ≈ 200-250 mg of iron
Classical Oral iron Maximal daily absorption 10 mg: for a patient
with Hb 10 g/dL, treatment for 3-4 months
Intravenous iron
Overcomes hepcidin blockage
High single doses at once
TID (mg) = (Hbtarget- Hbbaseline) x Weight x 2.4 + 500

“ORTHODOX” Iron supplementation
Orthopaedic, gynaecologic, colo-rectal.
 Preoperative IV iron (Grade 2B)
Orthopaedic, gynaecologic, cardiac
(± rHuEPO).
 Perioperative IV iron (Grade 2B)
ID or low iron stores (ferritin <100 ng/mL),
if there is enough time.
 Preoperative oral iron (Grade 2B)
No recommended.
 Postoperative oral iron (Grade – 1B)
Seville Document Update. Blood Transfusion 2013.© Prof. M. Muñoz/Cortesy Prof Muñoz

A PRAGMATIC APPROACH
Balgrist University Hospital, Zurich (2009 - 2011)
Theusinger, et al. Blood Transfusion 2014; 195-203
Indication of
MOS
Anaesthetic
assessment
(4-6 weeks prior
surgery)
Contact
Family Doctor
Hb
<13 g/dL
Hb
<13 g/dL 1000 mg iron, iv1000 mg iron, iv
40,000 U EPO, sc40,000 U EPO, sc
1 mg Vit B12, sc1 mg Vit B12, sc
5 mg/d Folate, oral5 mg/d Folate, oral
Hb
<13 g/dL
Hb
<13 g/dL 1000 mg iron, iv1000 mg iron, iv
40,000 U EPO, sc40,000 U EPO, sc
1 mg Vit B12, sc1 mg Vit B12, sc
Surgery
Postoperative
YES
NO
NO
YES
NO
YES
Hb <13 g/dLHb <13 g/dL
2W
n=4736
n=867
n=1985
(29,5%)
n=6721
n=1807
n=178
(9%)
n=26
(15%)
n=152
n=0 Cell salvageCell salvage
Topical haemostaticsTopical haemostatics
Restrictive transfusion
(Hb <8 g/dL ± signs)
Restrictive transfusion
(Hb <8 g/dL ± signs)
Meticulous haemostasisMeticulous haemostasis
Immediate preoperative
assessment
Modified © Prof. M. Muñoz/Cortesy

Surg Today (2005) 35: 36-40
ABT intraOP 27,4% vs 9,4%
Iron supplementation was given for at least
2 weeks preoperatively to 32 patients
whose Hb level at first presentation was
10.0 g/ dl (group A).
The iron preparation was sodium ferrous
citrate (200 mg/day), given orally after
meals in the morning and evening.

Transfus Med, 1997; 7:281 – 286
Iron pre-load for major joint replacement
C.M. Andrews, D.W. Lane, and J.G. Bradley
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
Anaemic Control Iron
Hbfall(g/dl)
Postoperative fall in Hb
with 95% confidence limits
P=0·008
Table 4. Homologous blood transfused
Mean units
transfused
Transfusion
rate
Anaemic 2·8 4/16 (25.0%)
Control 1·8 3/40 (7.5%)
Iron 1·7 0/35 (0.0%)
Anaemic ferrous sulphate 200 mg b.d. 4-weeks
Iron: ferrous sulphate 200 mg b.d. 4-weeks
Control: no treatment
Non anaemic
Preoperative oral iron

Patients and methods: We assessed the requirements for ABT in 156 consecutive patients
undergoing surgery for primary TKR, who received iron ferrous sulphate (256 mg/day; 80
mg of Fe2+
), vitamin C (1000 mg/day) and folic acid (5 mg/day) during the 30-45 days
preceding surgery, and who were transfused if Hb <80 g/L and/or clinical signs/symptoms
of acute anaemia or hypoxemia (Group 2).
A previous series of 156 TKR patients serves as a control group (Group 1).
- Preoperative oral iron

Patients and methods: We report a randomised, controlled trial of oral ferrous
sulphate 200 mg TDS for 2 weeks’ pre-operatively versus no iron therapy.
Patients diagnosed with colorectal cancer were recruited from out-patient
clinic and haematological parameters assessed. Randomisation was co-
ordinated via a telephone randomisation centre.

Seville Document Update. Blood Transfus 2013; 11:585-610.
The "ORTHODOX" approach
The "PRAGMATIC" approach
The "OPPORTUNITY" approach
 Very short-term perioperative IV iron ± ESA
Beris et al. NATA Consensus IV iron. BJA 2009;100: 599-604.
What can we do if
this time-frame in not available?
© Prof. M. Muñoz/Cortesy Modified

Transfusion. 2013 Apr 15. doi: 10.1111/trf.12195. [Epub ahead of print]
4 Spanish hospitals (October 2002 – December 2011)
Muñoz et al. Transfusion 2014; 54: 289 – 299.
Patients included n=2547

Respect to control, very short-term perioperative IV iron administration, with
or without rHuEPO, significantly reduced (*p<0.01):
No clinically relevant AEs were observed.
The scheduled IV iron dose (200-600 mg) may not cover total iron loss,
especially in patients with preoperative iron deficiency.
Preoperative rHuEPO was only administered in 351 out of 1059 patients
presenting with Hb level <13 g/dL and no contraindication.
Transfusion(%)
PostOPinfection(%)
30dmortality(%)
Hospitalstay(days)

ANEMIA Y “PATIENT BLOOD MANAGEMENT”

Postoperatorio
ANEMIA Y “PATIENT BLOOD MANAGEMENT”

Seville’s Document Update
We do not recommend the use of (classical) oral iron
in the early postoperative period for reducing ABT
rate or hastening the recovery from anemia
- Postoperative oral iron
1B
• In 6 out of 7 RCTs of non iron deficiency patients who underwent
elective or non elective orthopedic surgery or cardiac surgery, oral
iron supplementation for 4-10 weeks did not improve Hb levels
with respect to placebo.
• Moreover, only 1 out of 7 RCTs patients recovered baseline Hb
levels after 8 weeks on oral iron.
• Up to 30% of patients experienced adverse side effect to oral iron
(mostly gastrointestinal). Up to 10% of patients discontinued
therapy due to side effects.

FINAL COMMENTS

“The safest blood transfusión is….the one don´t given”
Please!, DO SOMETHING! TREAT THE ANAEMIA WISE AND NICELY!

PBM. Preoperative Anemia Management, Dr García Erce. Roma 2015

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