Anemo 2010 inghilleri anemie preoperatorie valutazione e trattamento

1. Anemie preoperatorie:
Valutazione e trattamento
1
Dott. Giovanni Inghilleri
U.O. SIMT
A.O. Fatebenefratelli e Oftalmico
Milano

2. 2
Role of preoperative anemia evaluation and
correction in surgery?
• Much of the variability in transfusion need
for a given surgery lies with patient
variables and not with surgical variables.
• When performed by an experienced
surgeon, a given type of surgery will result
in similar blood loss for most patients,
despite significant differences in patient
blood volume or starting hematocrit.
Palmer T, Anesth Analg 2003;96:369 –75

3. • Aim of the study:
to analyse the clinical factors that would be useful in
predicting patients who would require blood transfusion.
• Evaluated parameters were:
age, gender, body weight, operation, pre-op Hb, actual
blood loss, postop Hb level, whether a patient developed
symptoms of anaemia (e.g. shortness of breath, dizziness or
weakness), whether transfusion was administered and, if so,
the number of units transfused.
• There were no autologous donations.
4

4. 5
• The univariate analysis revealed a significant
relationship between postoperative blood Tx and
pre-op Hb levels (P=0.001), weight (P= 0.019)
and age (P=0.018) and not gender (P=0.47).
• However, multivariate analysis identified a
significant relationship only between the need for
transfusion and the pre-op Hb (P=0.0001) with
weight (P=0.169) and age (P=0.058) being
discounted as significant factors

5. Univariate analysis
relationship between Tx and
•Preop Hb (p = 0.0001)
•Duration of surgery (p= 0.0001)
•Weight (p= 0.002),
•Height (p = 0.019),
•Gender (p=0.0056).
Multivariate analysis
relationship only between TX and
•Preop Hb (p = 0.0001)
•Weight (p = 0.011);
7
% Pts transfused
• Hb < 13 g = 69%
• Hb 13-15g = 36%
• Hb > 15 g = 13%
J Bone Joint Surg Am 2002; 84-A: 216–20

6. 8
Anemie preoperatorie: Valutazione e
trattamento
Definition
According to WHO:
• Hb < 13 g/dL in men
• Hg < 12 g/dL in women

7. 9
Anemie preoperatorie: Valutazione e
trattamento
Prevalence
In general population (NHANES study in US):
– Overall: 4.4 – 5.9% of general population
– Age > 65: 11% of men and 10.2% of women
In surgical patients
– 5% -75% of elective surgical Pts (Goodnough
et al 2005)
– 24% of elective orthopedic pts in Belgium
(Van Linden et al, TATM 2010)
– 35% of elective orthopedic pts in US audit
(Wilson A, 2004)

8. 10
PPrreeooppeerraattiivvee AAnneemmiiaa
Distribution of baseline Hct orthopedic surgical patients operated at
Gaetano Pini Orthopedic Institute in 1997
Baseline Hct
N° pts 20.5% -
29.9 %
30% -
33.9%
34% -
39.9%
40% -
55.9%
Total 2183 6.% 12% 46% 36%
Female 1522 6.5% 13.3% 54.6% 25.6%
Male 661 4.5% 7.5% 27% 61%
Arthrosis 1298 1.5% 5.5% 48% 45%
Reumat . Art hrit . 82 7% 18% 52% 23%
Cancer 103 14% 6% 38% 32%
Sepsis 57 14% 28% 30% 8%
Other 643 9.5% 17.5% 42% 31%
Mercuriali F, Inghilleri G, Biffi E. Int J Artif Organs 2000; 23: 221-31

9. 11
EEvvaalluuaattiioonn ooff AAnneemmiiaa
The evaluation of the anemic preoperative patient should
always begin with a thorough history and physical exam.
History
– Symptoms of bleeding (menstrual blood loss,
hematochezia or melena, hematemesis, hemoptosys,
hematuria)
– Symptoms of underlying illness (malignancy,
renal failure, endocrinopathies [thyroid disorders],
infections, liver disease)
– Past history (prev Hb values and therapies,
splenectomy, trasnsfusions, blood donation)
– Social history (occupational hazards, dietary
habits, alchol and illicid drug use)

10. 12
EEvvaalluuaattiioonn ooff AAnneemmiiaa
The evaluation of the anemic preoperative patient should
always begin with a thorough history and physical exam.
Physical examination
Focus on manifestations and potential etiology of
anemia:
– Pallor of the skin
– Jaundice
– Signs of bleeding,
– Purpura,
– Petechiae
– Hepatosplenomegaly,
– Lymphadenopathy
– Pelvic and rectal examination may need to be
performed to evaluate sources of blood loss

11. 13
EEvvaalluuaattiioonn ooff AAnneemmiiaa
Diagnostic evaluation
Initial laboratory testing
– Complete blood count
– Reticulocyte count
– Peripheral blood smear
Additional exams (selected on the basis of initial testing
results, history and physical examination)
– Iron metabolism parameters (serum ferritin, serum iron,
transferrin saturation)
– Vit B12, Folate
– CPR
– Fecal occult blood test
– Endoscopic testing
– Renal, Liver, thyroid function parameters
– Bone marrow biopsy
– DAT, Aptoglobulin, Abnormal Hb.

12. 14
Patel MS, Carson JL. Anemia in the preoperative
patient.
Anestesiology Clin 2009; 27: 751-60

13. 16
Iron deficiency anemia (IDA)
• IDA is the most common nutritional deficiency
around the globe
• > 30% of anemia due to iron deficiency
Diagnosis
Serum Ferritin < 30 ng / dL *
Serum iron < 40 - 60 μg / dL
Transferrin saturation < 15 - 20%
* Concomitant evaluation of CPR has been suggested to
identify falsely elevated ferritin value secondary to
concurrent inflammation (Yang et al Am J Clin Nutr. 2008; 87:1892)

14. 17
Iron deficiency anemia (IDA)
Further parameters
• Soluble transferrin receptors (sTfR)
– Reflects erythropoiesis. Not affected by inflammation. Advantage
over Ferritin not fully demonstrated
• Ratio between sTfR and Ferritin (sTfR-F ratio)
– Helpful in evaluating IDA in patients with anemia of chronic
inflammation
• Zinc protoporphyrin/heme ratio (ZPP/H)
– Reliable in reflecting the bone marrow iron status. Lacks ability
to distinguish between ACD and IDA
• Reticulocyte hemoglobin content
– Early indicator of the response to iron therapy

15. 19

16. Iron deficiency without anemia
Potential role of MCV as a screening marker to detect ID conditions in
20
blood donors and surgical patients (evaluated donors n° = 2301)
MCV value
< 80 < 84 <86
N° of cases 63
(2,7%)
227
(9.8%)
467
(20%)
Mean Ferritin value 32+47 48+60 62+77
Median ferritin val. 13 24 37
N° of cases with
Ferritin <30 ng/mL
50
(79%)
132
(58%)
211
(45%)
Data from Niguarda Hospital and AVIS Comunale Milano - 2006

17. 21
Iron deficiency anemia (IDA)
Treatment
• Oral iron support
– Iron is most easily given in the oral form.
– The least expensive form is ferrous sulfate.
– Provide 65mg of iron per 325 mg tablet.
– Dose: in adult 150-200 mg of elemental iron per day.
– Better absorption in acidic gastric env (+ Ascorbic Ac
avoid antacid.
– Reticulocytosis in 7-10 days.
– Increase of Hb by 1 g/dL every 2-3 weeks.
– Helicobacter Pylori infection and chronic gastritis limit
the efficacy

18. 22
Best Practice & Reserch Clinical Haematology 2005;18: 319-332

19. 23
Chertow GM, et al.
Update on adverse drug events
associated with parenteral iron.
Nephrol Dial Transplant (2006) 21: 378–382
Life threatening events x million doses
Ferro
Saccarato
Ferro
Glucon.
Ferro
destrano

20. Trattamento della carenza marziale
Esperienza Gaetano Pini
Risultati ottenuti in Pz sideropenici con basso Hct trattati con Fe IV
24
Pz valutati 1186
Pz trattati con Fe IV 52 (4.4%)
Età (anni) 44±15
Ferritina Basale 24.2±17
Sideremia 62.4±24
MCV 82±8.5
Hct basale 36.2±2
Fe somministrato (mg) 898±428
Hct dopo terapia 38.9±2.7
Produzione di RBC (mL) 157±87

21. 25
Iron
deficiency
anemia
(IDA)
Treatment
• Underlying cause
must be treated;
• Recommendations
for unexplained IDA
include endoscopy

22. 26
G. Inghilleri
Anemia of chronic disease
immune driven
a)Impaired proliferation
of erythroid progenitors
cells;
b)Blunted erythropoietin
response
c)Disregulation of iron
homeostasis;

23. 27
Clinical conditions
associated with ACD
• Heart failure
J Am Coll Cardiol 2008;52:501–11
• Critically ill patients
Transf Med Rev 2006; 20:27-33
• Ageing
Blood Rev 2001; 15(1): 9-18
• Major joint arthrosis
Br J Anesth 2007; 99:801-8

24. 28
Diagnosis of ACD

25. 29
Treatment of ACD

26. 30
EErryytthhrrooppooiieettiicc SSttiimmuullaattiinngg AAggeennttss
Eritropoietin (EPO)
• Acts synergistically with IL-3 and GM-CSF
to expand the BFU-E compartment
• Stimulates proliferation, maturation, and
hemoglobin formation by committed
erythroid progenitors (CFU-E)
• Stimulates the early release of
reticulocytes from marrow into the
circulation
• Inhibit apoptosis

27. 31
rHuEPO in surgery
The response to treatment is not
dependent on patient age or gender, but
on the administered rHuEPO dose and the
availability of essential nutrients, such as
iron (the use of IV iron may allow for a
reduction of total rHuEPO dose), folate or
vitamin B12.
Approximately Hb increases by 1-2 g/dL
per week of treatment with 200U-600U/Kg
of rHuEPO

28. 32
rHuEPO in surgery
Perioperative rHuEPO administration is
indicated for patients scheduled for elective
orthopaedic surgery where moderateto-high
blood loss is expected when their Hb is
> 100 g/l and < 130 g/l.
Two prospective RCTs (896 patients) and
one case–control study (770 patients) found
that preoperative rHuEPO administration
significantly reduced ABT rate (AOR 0·63;
95% CI 0·21–0·49)

29. 33
Study 1
• Indication for PABD was based
on comparison of each patient’s
RBC reserve with mean
estimated perioperative RBC
loss:
• PABD indicated if RBC reserve
was < 800 mL (THA) or <1000
mL (TKA), Hct > 33%, life
expectancy of 10 yr, no medical
contraindication, and consent of
the patient.
• 2 AB units were collected
preop.
Study 2
• EPO instead of PABD when
Hct <37%, life expectancy > 10
yrs
• 3 weekly SC doses of 600
UI/kg .
• Oral ferrous sulfate 320 mg
daily in association with EPO.
• No PABD in case of baseline
Hct > 39%. PABD only in Pts
with baseline hct between
37%-39%. Triggers for any
transfusion (autologous or
allogeneic) were identical

30. 34

31. rHuEPO in surgery
rHuEPO 300 UI/Kg For 10 days For 4 days
rHuEPO 40.000UI
or 600 UI/Kg
35
Preoperative use of rHuEPO: EEaacchh aarrrrooww iinnddiiccaatteess SSCC
rrHHuuEEPPOO pplluuss IIVV iirroonn iinnffuussiioonn
week -3 -2 -1 0 (surgery) +1
week -3 -2 -1 0 (surgery) +1

32. Methods
• Application of a restrictive TT (Hb < 8 g/dl)
• Perioperative administration of IV iron sucrose (3 x 200 mg/48
h) (group 1, n=115).
• Some Pts received preop rHuEPO (40 000 IU sc) on
admission (group 2, n=81).
Results
• Significant differences in periop ABT (60% vs. 42%, for
groups 1 and 2, respectively; P=0.013).
• Postoperative Hb on postop days 7 and 30 was higher in
group 2 than in group 1.
• Administration of rHuEPO did not increase postop
complications or 30-day mortality rate.
36
Vox Sanguinis (2009) 97, 260–267

33. 37
rHuEPO in surgery
Safety
The FDA has recently stated that the use of
ESAs may increase the risk for thrombotic
events in the peri-surgical setting
Jerkins JK. 2007 Erythropoiesis stimulating agents
http://www.fda.gov/ola/2007/esa062607.htlm
However, this occurred mostly in pts with
preoperative Hb > 13 g/dl

34. 38
6
5
4
3
2
1
0
rHuEPO in surgery
IIrroonn SSuupppplleemmeennttaattiioonn
Oral vs IV iron in rHuEPO treatment
Placebo rHuEPO 300IU/kg rHuEPO 600IU/kg
N° of predeposited units
Oral Iron
IV iron
700
600
500
400
300
200
100
0
Placebo rHuEPO 300IU/kg rHuEPO 600IU/kg
mL of RBCcollected
Oral Iron
IV iron
Mercuriali F, Zanella A, Barosi G, et al Use of erythropoietin to increase the volume
of autologous blood donated by orthopedic patients. Transfusion 1993; 33: 55-60

35. Detection, evaluation and management of
preoperative anemia. NATA Guidelines (2010)
• We recommend that elective surgical
patients have an Hb level determination as
close to 28 day before the scheduled
surgical procedure as possible;
• We suggest that patient’s target Hb before
elective surgery be within the normal
range (female 12 g/dL; male 13 g/dL)
according to WHO criteria
Goodnough LT, Earnshaw P, Maniatis A. NATA Guidelines Working Group
TATM 2010; 11 (suppl 2): 10-11
39

36. Detection, evaluation and management of
preoperative anemia. NATA Guidelines (2010)
• We recommend that laboratory testing be
performed to further evaluate anemia for
nutritional deficiencies, chronic renal
insufficiency, and/or chronic inflammatory
disease;
• We recommend that nutritional deficiencies be
treated;
• We suggest that ESA be used for anemic patient
in whom nutritional deficiencies have been ruled
out and/or corrected
Goodnough LT, Earnshaw P, Maniatis A. NATA Guidelines Working Group
TATM 2010; 11 (suppl 2): 10-11
40