Download Renal Anaemia Guidelines

Clinical Guidelines for the
management of renal anaemia
with erythropoietin and iron in
pre-dialysis and dialysis patients
Type: Clinical Guideline
Register No:
Status:
National Kidney Federation (KDOQI) Guidelines
(2007), Renal Association Guidelines (2010),
NICE clinical guideline 114 (2011)
Developed in response to:
Contributes to CQC Outcome number:
Consulted With
Lisa Whitehouse
Dr A Chan
Dr S Abeygunasekara
Dr A Ali
Professionally Approved By
Post/Committee/Group
Anaemia Coordinator
Nephrologist
Lead Clinician, Renal
Nephrologist
Dr A Chan
Version Number
Issuing Directorate
Ratified by:
Ratified on:
Executive Board Sign Off Date
Implementation Date
Next Review Date
Author/Contact for Information
Policy to be followed by (target staff)
Distribution Method
Related Trust Policies (to be read in
conjunction with)
Date
21.4.2015
1.3.2012
1.3.2012
1.3.2012
4.0
April 2018
Sarah Cox
All Trust staff
Intranet
Document Review History
Review No
1.0
2.0 Update targets & formatting
3.0 Changed IV iron preparation, Hb units
Reviewed by
Catherine Morgan
Sarah Cox
Lisa Whitehouse/Sarah Cox
Review Date
July 2007
February 2012
April 2015
It is the personal responsibility of the individual referring to this document to ensure that they are
viewing the latest version which will always be the document on the intranet
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1. Purpose
2. Equality and diversity
3. Scope
4. Infection control
5. Staffing and Training
6. Renal anaemia
7. Audit
8. Appendices:
Appendix 1: Iron supplementation in patients with CKD (pre-dialysis) and in those on
peritoneal dialysis
Appendix 2: Administration of IV iron in CKD and PD patients
Appendix 3: Prescription for Intravenous Iron for Peritoneal Dialysis, CKD (pre dialysis)
and Transplant Patients
Appendix 4: Intravenous iron protocol in HD patients
Appendix 5: Algorithm for assessment of poor response to erythropoiesis-stimulating
agents
Appendix 6: ESA therapy-initiation and monitoring
9. Contacts in the renal team
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1.0
Purpose
The purpose of this guideline to reduce the morbidity and mortality associated with renal
anaemia with appropriate and timely assessment and treatment with iron and erythropoiesisstimulating agents (ESA’s).
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2.0
Timely / early referral to anaemia management sister
Optimise effective use of iron and ESA’s
Reduce the need for blood transfusion
Reduce the risk of transmission of blood borne viruses, iron overload and
sensitisation of patients to future transplants
Improve quality of life
Reduce cardiovascular risk
Reduction in hospitalisation
Equality and Diversity
MEHT is committed to the provision of a service that is fair, accessible and meets the needs
of all individuals.
3.0
Scope
3.1
This guideline applies to adult (aged over 16) patients with anaemia caused by
chronic kidney disease (CKD) within Mid Essex and West Essex.
3.2
Medical staff working in the nephrology service at MEHT and anaemia nurse
specialists (if registered non-medical prescriber) may prescribe according to this
policy.
4.0
Infection Control
Please refer to Trust infection control policies and guidelines.
5.0
Staffing and Training
See section 3.2 above
6.0
Renal anaemia
6.0.1
Renal anaemia is a cause of significant morbidity and to a lesser extent mortality in
patients with chronic kidney disease. Anaemia in CKD is primarily due to the lack of
erythropoietin and iron (including functional iron deficiency). Anaemia usually
develops as the GFR falls below 35 ml/min and worsens with declining GFR.
Effective management is possible using oral and intravenous iron preparations and
genetically engineered erythropoiesis-stimulating agents (ESA’s). Increasing
haemoglobin levels results in major improvements in quality of life, exercise capacity,
cognitive function, sexual function, nutrition, sleep patterns, immune responsiveness
and cardiac status.
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To ensure safe and effective management of renal anaemia, treatment should follow
established guidelines. The National Institute for Health and Care Excellence (NICE)
updated guideline Anaemia management in people with chronic kidney disease was
published in February 2011, an update is expected in 2015.
6.0.2 Standards
The Renal Association clinical practice guidelines (November 2010) recommend that:

Haemoglobin (Hb) levels should be tested at least annually in CKD patients.

All patients with chronic anaemia associated with chronic kidney disease (CKD)
should be investigated for possible treatment, irrespective of the stage of kidney
disease or requirement for renal replacement therapy.
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Anaemia should be evaluated in CKD patients with Hb < 110 g/L or symptoms
attributable to anaemia.
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CKD should be considered as a possible cause of anaemia when the GFR is < 60
ml/min/1.73m2. It is more likely to be the cause if the GFR is < 30 mls/min/ 1.73m2
(< 45 in diabetics) and no other cause, i.e. blood loss, folic acid or vitamin B12
deficiency, is identified.
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Initial clinical and laboratory evaluation of anaemia should be performed prior to
initiation of treatment for anaemia in CKD patients.
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Treatment with ESAs should be offered to patients with anaemia of CKD who are
likely to benefit in terms of quality of life and physical function, and to avoid
transfusion in patients considered suitable for transplantation.
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Patients with CKD on ESA therapy should achieve Hb between 100-120 g/l.

ESA therapy should not be initiated in the presence of absolute iron deficiency
(ferritin <100 µg/l). In patients with functional iron deficiency, iron supplements should
be given prior to or when initiating ESA therapy.
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Adjustments to ESA doses should be considered when Hb is <105 or >115 g/l in
order to balance the benefit and safety to patients given the current evidence base.
These thresholds for intervention should achieve a population distribution centred on
a mean of 110 g/l with a range of 100-120 g/l.
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Serum ferritin should not exceed 800 µg/l in patients treated with iron, and to achieve
this iron management should be reviewed when the ferritin is > 500 µg/l.
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A definition of adequate iron status is a serum ferritin 200-500 µg/l in HD patients,
100-500 µg/l in non-HD patients, <10 % hypochromic red cells and transferrin
saturation (TSAT) >20 %.
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6.1
Diagnosis
6.1.1
The signs and symptoms of anaemia vary with severity and the period over which the
reduction in Hb develops. Anaemia of CKD may present with:
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Mild breathlessness on exertion
Lethargy / tiredness
Loss of appetite
 sensitivity to cold
 cognitive function / irritability
Note that due to its insidious onset anaemia associated with CKD is often asymptomatic
and only picked up on routine blood analysis.
6.2
Assessment and investigation
6.2.1 Haemoglobin
Anaemia should be investigated in patients with CKD if:
-Hb levels fall below 110 g/l in adults or
-They develop symptoms attributable to anaemia (such as tiredness, shortness of
breath, lethargy and palpitations).
6.2.2 Iron Studies
Serum ferritin is an iron storage protein which provides an indirect measurement of stored
iron. A low serum ferritin is always indicative of iron deficiency. A high serum ferritin (> 800
g/l) does not always indicate iron overload because levels are also raised if there is
hepatocellular injury or inflammation.
Transferrin is a protein that transports iron from stores to bone marrow. Transferrin
saturation (TSAT) gives a measure of iron available to the bone marrow. This is a useful
parameter for detecting functional iron deficiency, which can exist despite normal or raised
ferritin values.
% TSAT =
serum iron
Total iron binding capacity (TIBC)
x 100
Iron studies should not be taken within one week of receiving IV iron.
6.2.3 Assessment of Anaemia should include the following:
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Haemoglobin
Red cell indicies (MCV)
Absolute reticulocyte count
Serum ferritin
%TSAT (Serum iron and TIBC)
Serum B12
Serum folate
CRP
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If no other cause for anaemia can be found and eGFR is < 30 ml /min (non-diabetics)
and 45 ml/min (diabetics) the CKD is the most likely cause.
6.3
Treatment
6.3.1 Erythropoiesis-stimulating Agents
Not all patients with CKD will require ESAs.
ESAs should be given to all patients with CKD whose Hb levels fall consistently
below 110 g/l and where other possible causes of anaemia have been excluded.
Current brand available in Mid Essex (also for our Harlow patients) is Epoeitin alpha
(Eprex) both for use IV in haemodialysis or SC in PD or pre-dialysis.
6.3.2 Iron Supplementation
All patients receiving ESAs should be given iron supplementation.
Oral iron
Oral iron is often poorly absorbed and should not be used in haemodialysis patients.
An exception may be made if a patient is intolerant to all preparations of IV iron, in
which instance it may be used in combination with vitamin C.
IV iron
Ferric carboxymaltose (Ferinject®) should be used for low clearance, conservative
management and home therapies patients.
Iron sucrose (Venofer®) should be used for haemodialysis patients.
Iron Dextran is not generally recommended, however patients allergic to iron sucrose
may be given Iron dextran.
See algorithm for route and regime for administration of iron (Appendix 2 & 3)
6.4
Targets
As per NICE clinical guideline 114 (February 2011)
6.4.1 Haemoglobin Targets
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Patients with CKD should maintain an Hb range between 10-12 g/dl or reach this
within 4 months of being seen by a nephrologist regardless of age, ethnicity or
gender.
To keep the Hb level within the range, do not wait until Hb levels are outside the
range before adjusting treatment (for example, take action when Hb levels are within
5 g/l of the range’s limits).
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6.4.2 Iron Targets
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Patients with CKD need sufficient iron to maintain a haemoglobin > 110 g/l
All patients should have;
o Serum ferritin > 100 µg/l
o TSAT > 20%
Aim for target serum ferritin 200 – 500 µg/l
Aim for target TSAT 30 – 40 %
Upper limit for ferritin should be 800 µg/l (note that ferritin is an acute phase reactant
and thus concentrations usually increase 2 to 4 fold in inflammatory states).
6.4.3 Failure to respond
Definition of inadequate response:
Target haemoglobin (> 11 g/dl) is not achieved whilst receiving doses of greater than
300 iu/kg/week of epoetin alpha or a continued need for high doses to maintain the
target.
Approximately 90 – 95 % of patients receiving erythropoietin therapy will show a
satisfactory response with improvement in their anaemia associated with secondary
benefits in terms of quality of life. A small but important minority of patients, however,
fail to respond satisfactorily to standard doses of ESAs. Major causes of ESA
resistance include:
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Iron deficiency
Infection
Inflammation
Occult blood loss
Aluminium toxicity
B12 or folate deficiency
Haemolysis
Inadequate dialysis
Marrow disorders
Haemoglobinopathies (e.g. sickle cell)
Pure red cell aplasia (PRCA)
For assessment of poor response see algorithm (Appendix 5)
In case of infection:
Please contact a renal physician; do not stop ESA / iron
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6.5
Blood transfusion in Patients with CKD
6.5.1
Red blood cell transfusions are indicated in severely anaemic patients with
recognised symptoms or signs of anaemia, e.g. the patient with acute blood loss
associated with haemodynamic instability or the patient with severe angina. The
erythropoietin resistant patient with blood loss whose haemoglobin concentration
decreases to critical levels should also be considered for blood transfusion.
6.5.2
Blood transfusion should be avoided if possible in patients likely to have a transplant
in the future or actually on the transplant waiting list. If transfusion is required then
steps to minimise MHC sensitisation such as leucocyte filtration can be taken. Bloods
should be sent to the tissue typing laboratory for assessment of panel reactive
antibodies (cytotoxic antibodies) 2 and 4 weeks following transfusion.
7.0
Audit
7.1.1
The anaemia nurse specialist will regularly run a report on Hb and iron levels in predialysis renal patients via the renal programme, eMed, which imports results from
MEHT Review. She will then alter their ESA or iron prescription accordingly.
7.1.2
Haemodialysis patients’ blood results will be checked monthly by a nurse and a
consultant nephrologist, and their iron/ESA prescription amended accordingly.
8.0
Appendices
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Appendix 1
IRON SUPPLEMENTATION IN PATIENTS WITH CKD (PRE-DIALYSIS AND CONSERVATIVE MANAGEMENT)
AND IN THOSE ON HOME DIALYSIS THERAPIES
Hb must be < 140 g/l
ORAL IRON
Should not be considered in patients on ESA therapy or those with Hb < 120 g/l (unless intolerant to IV iron). Patients on EPO therapy and haemodialysis will
require a higher degree of iron replacement than can be delivered by oral supplementation in order to maintain recommended Hb levels.
NOT ON EPO
Hb 120 – 140 g/l
Ferritin < 150 g/l
and / or TSAT < 20%
If no improvement in iron
status or Hb after 6
weeks or not tolerated,
discontinue and consider
IV therapy
Start ORAL IRON
200 mg ferrous
sulphate up to TDS
IV IRON
Oral iron should be discontinued when the patient is receiving IV iron
FERRITIN
Ferritin < 150 g/l
TSAT < 20 %
Ferritin 150 – 500 g/l
TSAT < 20 %
Ferritin < 150 g/l
TSAT > 20 %
GIVE IV IRON as per
protocol
Ferritin > 500 g/l
TSAT < 20 %
Discuss with
Nephrologist
Repeat Hb, Ferritin, iron and TIBC 2 – 4 weeks post IV iron infusion
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Ferritin 150 – 500 g/l
TSAT > 20 %
Ferritin > - 500 g/l
TSAT > 20 %
DO NOT GIVE IV IRON,
consider ESA if Hb < target
Appendix 2
ADMINISTRATION OF IV IRON IN CKD & PD PATIENTS
This guideline is for the administration of IV iron in patients with CKD or on peritoneal dialysis
Preparation
Ferric carboxymaltose (Ferinject®) 500mg/10ml
General Information
 All qualified nurses who hold their ‘IV Certificate’ can administer all iron infusions
 All side-effects / adverse reactions must be reported to a doctor
 Peritoneal dialysis patients will be treated by the PD nurses
 In-patients on ward will be treated by the ward nurses
 Patients with CKD and transplant patients will be treated in the iron clinic
Resuscitation drugs should always be easily available during the administration of IV iron
Side effects
Very rarely anaphylactic reactions. Most anaphylactoid reactions will be reactions such as headache,
hypotension, metallic taste, nausea and vomiting.
If a patient suffers side-effects consider reducing the dose and / or rate of administration of IV iron
after consulting a doctor.
In the event of an anaphylactic reaction, summon medical assistance immediately. In the event of
cardiac / respiratory distress follow the normal cardiac arrest procedure.
Administration
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A test dose is no longer recommended, however the patient should be monitored both during
and for 30 minutes post-infusion.
Ensure prescription is signed and checklist is completed before giving IV iron (Appendix 3).
Site a blue (23G) butterfly or a cannula in a vein preferably in the hand, flush slowly with 5 ml
0.9% sodium chloride.
Patients requiring IV iron (as per algorithm) should receive a dose of 1000 mg Ferinject®.
Add 20 ml Ferinject® (1000 mg) to a 100 ml bag of 0.9 % sodium chloride and give this 120 ml
solution over 15 minutes (pump speed 480 ml/hour). Once the entire dose has been infused, flush
with a further 5 ml 0.9 % sodium chloride.
Subsequent doses
Re-check FBC and iron stores for response 4 weeks post-infusion. If necessary give a further dose
as indicated in the table below. For example, a 75 kg patient with Hb > 100 g/l but iron-depleted, give
500 mg in addition to the 1000 mg already given.
Haemoglobin (g/l)
Pt body wt 35 kg to <70 kg
Pt body wt ≥70 kg
< 100 g/l
≥ 100 g/l
500 mg
Discuss with consultant
1000 mg
500 mg
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Appendix 3A
Prescription for Intravenous Iron, (Ferinject®) for Peritoneal Dialysis (PD),
CKD (pre dialysis) and Transplant Patients-Checklist
Name: [Patient First Name] [Patient Last Name]*
DOB: [Patient DoB]*
Hospital Number: [Patient HNo]* NHS No: [Patient NHS No]*
This checklist should be completed before each administration of IV iron.
Test*
Haemoglobin (g/l)
Ferritin (µg/l)
TSAT (%)
Weight (kg)
ESA dose (units)
Blood pressure (mmHg)
*[data imported from eMed]
Level
Date of test
Pre:
Post:
□ Patient’s identity confirmed
□ Is the patient on antimicrobial treatment?
Stick High Impact Intervention
□ Check for allergies
label here
□ Patient informed about:
-Why they need IV iron
-Potential side effects of IV iron
□ Patient consent given
□ Anaphylaxis treatment available
□ Peripheral venous access inserted as per local policy
□ Device used butterfly / cannula (delete as applicable)
□ Site of IV access:
□ Patient has stopped oral iron now commenced on intravenous iron
□ Observe patient for 30 minutes post-infusion
□ Agree plan for follow up blood test in four weeks’ time
Signature:
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Name:
Date:
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Appendix 3B
Prescription for Intravenous Iron, (Ferinject®) for Peritoneal Dialysis (PD),
CKD (pre dialysis) and Transplant Patients
Patients requiring IV iron (as per algorithm) should receive a dose of 1000 mg Ferinject ®.
Site a blue (23G) butterfly or cannula in a vein preferably in the hand, flush slowly with 5 ml 0.9%
sodium chloride.
Add 20 ml Ferinject® (1000 mg) to a 100 ml bag of 0.9 % sodium chloride and give this 120 ml
solution over 15 minutes (pump speed 480 ml/hour). Once the entire dose has been infused, flush
with a further 5 ml 0.9 % sodium chloride.
Subsequent doses
Re-check FBC and iron stores for response 4 weeks post-infusion. If necessary give a further dose
as indicated in the table. For example, a 75 kg patient with Hb > 10 but iron-depleted, give 500 mg in
addition to the 1000 mg already given.
Haemoglobin (g/l)
Pt body wt 35 kg to <70 kg
Pt body wt ≥70 kg
< 100 g/l
≥ 100 g/l
500 mg
Discuss with consultant
1000 mg
500 mg
In the event of an allergic reaction to IV iron
Date
Date
Drug
Route
Dose
Hydrocortisone
IV
100 mg
Chlorphenamine
IV
10 mg
Dose
Number
1
Signature
Dose
Ferinject®
1000 mg (20 ml) added to
100 ml sodium chloride 0.9%
Given by signature
Prescribers
signature
Given by
Signature
2
For Patients also requiring erythropoietin
Date
Dose
Number
1
Dose
Eprex®
Hb
Prescribers
signature
Given by Signature
2
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Appendix 4
INTRAVENOUS IRON PROTOCOL FOR HAEMODIALYSIS (HD) PATIENTS
This protocol is for all patients receiving haemodialysis at Broomfield Hospital dialysis unit.
Administer remaining 200 mg (10 ml) Venofer® directly into the bubble trap over 5-10
minutes.
Regular doses of Venofer® are based on the patient’s serum ferritin level and are dosed
accordingly.
Serum ferritin
0 -100 µg/l
200 mg
Venofer®
Serum ferritin
Serum ferritin
101 – 300 µg/l
301 – 400 µg/l
200 mg
200 mg
Venofer®
Venofer®
3 times per
week
2 times per
week
Weekly
Serum ferritin
401 – 500 µg/l
100 mg
Venofer®
Weekly
Serum ferritin
501 – 800 µg/l
100 mg
Venofer®
Fortnightly
Serum ferritin levels greater than 800 µg/l should be discussed with the doctor.
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Appendix 5
ALGORITHM FOR ASSESSMENT OF POOR RESPONSE TO
ERYTHROPOIESIS-STIMULATING AGENTS (ESAs)
ASSESS COMPLIANCE
Screen for iron deficiency
(Serum ferritin < 150 g/l or
TSAT < 20 %)
Give trial of IV iron as per
protocol

Reticulocyte count
CRP
Infection / inflammation
Adequacy of dialysis
Kt/V < 1.2 HD
Kt/V < 1.7 PD
PTH
B12 and folate
Serum aluminium
PSA
Hb electrophoresis
? On ACEI
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 (> 70 x 10 /L)
Investigate / treat for blood
loss / tests for haemolysis
Treat appropriately
Increase dialysis
Try high dose ESA
Epoetin alpha 30,000
units total weekly dose
Refer to haematologist /
Bone marrow
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Appendix 6
ESA THERAPY – INITIATION AND MONITORING
EPREX:
Pre-filled syringes containing 1000, 2000, 3000, 4000, 5000, 6000, 8000 or
10,000 units epoietin alpha (6 in a pack)
Frequency of administration – may be given 1 x, 2 x or 3 x per week
Route of administration
Epoietin (EPO) should be administered subcutaneously in pre dialysis and peritoneal dialysis
patients. According to patient characteristics, unit practice and preference EPO may be administered
either subcutaneously or intravenously in patients on regular haemodialysis, but the subcutaneous
route will usually lead to a lower dose of EPO being required.
When EPO is administered subcutaneously the site of injection should be rotated.
Initiating ESA Treatment
Starting dose 50 –150 units kg/week
Aim to increase haemoglobin by 10-20 g/l per month until target is met
Monitor haemoglobin every 2 - 3 weeks initially
If the haemoglobin increase is < 7 g/l after 6 weeks of starting ESA the dose should be
increased by 50 %
5. If the haemoglobin increase is > 25 g/l or exceeds target within 4 – 6 weeks of starting ESA, the
dose should be decreased by 25-50 %.
1.
2.
3.
4.
Maintenance
The maintenance dose will usually be approximately 50% of the starting dose.
Recommended total weekly doses:
CKD Pre-dialysis
Haemodialysis
CAPD
200 units/kg total weekly dose
75-300 units/kg total weekly dose
50 -100 units/kg total weekly dose
Once the target haemoglobin is met and is stable, haemodialysis and peritoneal dialysis patients
should have FBC measured every month and pre-dialysis patients can be monitored less often but
no longer interval than 2 – 3 months.
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9.0
Contacts in the Renal team:
Dr S Abeygunasekara
Dr AA Ali
Dr AY Chan
Lead Nephrologist
Nephrologist
Nephrologist
01245 514414
01245 514590
01245 514414
Out of hours a Nephrologist is available via switchboard:
01245 443673
Lisa Whitehouse
Anaemia Coordinator
01245 514364
Rebecca Culpin
Lead Nurse
01245 514430
Sarah Cox
Renal Pharmacist
01245 513507
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