Anemia Manejo

8/11/2019 Anemia Manejo

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A systematic approach to evaluation and

investigation is key to the successful manage-

ment of anaemia. Our Drug review considers

the various oral and parenteral treatments

available, followed by an analysis of prescrip-

tion data and sources of further information.

Anaemia continues to be a significant health prob-lem, occurring in 12 per cent of the population ofdeveloped countries. It has been known since ancienttimes: an early description of anaemia appears inPapyrus Ebers, a therapeutic manual from 1500BC, andchlorosis was well known to physicians in the mid-16th

century. Severe anaemia, as described in the past, israre in UK practice nowadays, but mild to moderateforms are common and require thoughtful, systematicevaluation and initial investigation in primary care.

A simple approach to understanding and classifyinganaemia is presented here to support the busy physi-cian achieve effective diagnosis, management andtriage of anaemias encountered in clinical practice.

Management principles

Anaemia is a sign of an underlying condition and nota complete diagnosis in itself. Appropriate evaluation,investigation and management of anaemia are basedon a systematic approach. Accurate diagnosis of iron-deficiency anaemia, for example, can be a key finding

www.prescriber.co.uk Prescriber 5 November 2012 25

Drug review Anaem

Guide to evaluation and treatment

of anaemia in general practiceAlastair Smith FRCP, FRCPath

SPL

CPD questions

available for

this article.

See page 42continued on page 28


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in identifying adult patients with a possible diagnosisof bowel cancer.

Any condition that can impair the production orincrease the rate of destruction or loss of erythrocytes

can result in anaemia if the bone marrow is not abto compensate for the rate of loss of red blood ce(RBCs). This situation can arise in nutritional deciencies, systemic disease, primary bone marr

disorders, autoimmune conditions, primary abnmalities of erythrocytes and blood loss.

The ease with which deficiency anaemia iron, foland vitamin B12 can be corrected may tempt empiritherapy or self-treatment, which can lead to significadiagnostic errors. Wherever possible the clinician shouaim to understand the cause of anaemia in a given in

vidual rather than resort to empiricism that may leadmissed or delayed diagnosis in many cases.

In the UK advice on possible causation and furthinvestigation and/or referral of unexplained or atyical anaemias can always be obtained through lo

haematology departments.

Pathogenesis of anaemia

The basic mechanisms of anaemia can be sumarised as: impaired ability of the bone marrow to produce sficient numbers of RBCs accelerated destruction or loss of RBCs combinations of both the above.

In Western populations anaemia is consideredbe present when the haemoglobin level is less th130g per litre in males and 115g per litre in female

Mean cell volume (MCV) a measure of averaRBC size (normal range 7898fl) is used to classanaemia and thus determine further investigation amanagement. This represents a functional approato dealing with anaemia in primary care. Table 1 illtrates the causes of anaemia classified by the MCV.

Low MCV hypochromic microcytic anaemiaAnaemia in this form arises from impaired haemogbin synthesis and is a result of reduced productioneither haem or globin. Decreased haem synthesis is seen in: Iron deficiency. The commonest worldwide cau

of anaemia and is due to iron losses exceeding intak Chronic disorders. Chronic infectious or inflammtory diseases or cancer can also cause anaemia impairing the utilisation of available iroParadoxically, in many of these conditions stored iris increased. There is also impaired responsivenesserythropoietin (EPO), the hormone that stimulaRBC production. Variable degrees of reduction in tMCV result, causing confusion with iron deficiency Disorders of impaired globin synthesis: alpha- abeta-thalassaemia syndromes resulting from inheritdisorders of globin synthesis. Homozygous for

28 Prescriber 5 November 2012 www.prescriber.co

Anaemia

Table 1. Causes of micro-, macro- and normocytic anaemias

Mic!oc'#ic anaemia" (lo& MCV)

Common

iron-deficiency anaemia (~60%)

anaemia of chronic disorders (~2030%)

haemoglobinopathies

thalassaemias

haemoglobin E trait and haemoglobin E disease

Rare

paroxysmal nocturnal haemoglobinuria

atransferrinaemia

antibodies to the transferrin receptor aluminium intoxication

sideroblastic anaemias

Mac!oc'#ic anaemia" (high MCV)

(chronic) alcohol excessa

vitamin B12 or folate deficiency

drug intake

haemolysis

liver disease

myelodysplasic syndromes

thyroid disease

unexplained/idiopathic

Rare

hypoplastic and aplastic anaemia

No!moc'#ic anaemia" (no!mal MCV)

acute blood loss

anaemia of renal failure

anaemia of chronic disorders

haemolytic anaemia

anaemia of liver disease (multifactorial)

anaemia of endocrine disease

early iron-deficiency anaemia

mixed iron and vitamin B12/folate deficiency (masked

megaloblastic anaemia)

structural variant haemoglobinopathies including

haemoglobins S, C and D

Rare

hypoplastic and aplastic anaemia

amacrocytosis without anaemia is a very common indica-

tor of excess alcohol intake


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result in serious, transfusion-dependent congenitalanaemia. Heterozygous trait forms typically producemicrocytosis with or without anaemia mild degreesof anaemia are more typically associated with the beta-thalassaemia trait.

HaemoglobinopathiesA variety of amino acid changesin the haemoglobin molecule are recognised, mostcommonly haemoglobins S, C and E. Some of thesecan present with a microcytic anaemia. However, theirpresence is usually apparent because of other clinical

problems in addition to anaemia, such as painful crisisin sickle cell anaemia. (See Haemolytic anaemiasbelow for further details.)

Sideroblastic anaemiasare rare disorders of haem syn-thesis that can result in microcytic anaemia. Lead poi-soning can also be a cause. Most commonly found inadults, sideroblastic anaemia is a form of myelodys-plastic syndrome.

Raised MCV macrocytic anaemiasThe macrocytic anaemias are usually subclassified asmegaloblastic and nonmegaloblastic based on findingsfrom bone marrow examination.

Megaloblastic anaemiasoccur whenever there is a sig-nificant deficiency of key substrates in the DNA syn-thetic pathways. Peripheral blood macrocytosis(increased MCV) results, together with varying degreesof anaemia. These anaemias occur in deficiencies ofcobalamin (vitamin B12, egpernicious anaemia) andfolate, and associated with drug therapy that interferes

with nucleic acid metabolism, egantineoplastic agents hydroxycarbamide, methotrexate and azathioprine.Excessive alcohol intake can occasionally producemegaloblastic changes on its own; these are usuallyassociated with nutritional deficiency of folic acid.

Macrocytic anaemias without megaloblastic marrchangesExcess alcohol intake is a common caualthough macrocytosis without anaemia is the more fquent manifestation. Co-existent nutritional deficien

of folic acid may also be a contributing factor in somcases. Liver disease, drug therapy (anticonvulsantschemotherapy), thyroid disease (thyrotoxicosis or moedema) and aplastic anaemia (a rare condition of faure of all marrow elements) may also be responsiband some forms of myelodysplastic syndrome may prent with an isolated macrocytic anaemia.

Normal MCV normocytic anaemiasAnaemia in this form is very common with many causincluding those that can cause microcytic chronic-dorder anaemias. The most important cause of acu

onset normocytic anaemia is acute blood loss, and tmust always be considered in initial clinical assessmeof anaemia as well as other causes. Additional possibcauses include EPO deficiency (associated with chronrenal dysfunction) and reduced responsiveness to EP

Haemolytic anaemiasHaemolytic anaemias result from increased red cdestruction; the lifespan of circulating RBCs is reduceand these may present with low, normal or raised levof MCV. The rate of RBC destruction exceeds the abiof the bone marrow to compensate, and worsenin

sometimes life-threatening, anaemia may ensue.In haemolytic anaemias serum bilirubin levels aoften, but not always, raised due to increased bredown of haemoglobin. Other markers of haemolyinclude a raised lactate dehydrogenase (LDH) and increased number of early red cells (reticulocytes)the peripheral blood.

The types of haemolytic anaemias encounteredUK practice are listed in Table 2.

Dilutional anaemia (pseudoanaemia)An increase in plasma volume will result in reduchaemoglobin concentration, haematocrit and RBC cou

without any decrease in the patients total RBC mass. Fexample, in pregnancy the haemoglobin level can falllow as about 100g per litre (physiologic anaemia of prnancy). No treatment is required. Hyperviscosity sydromes such as myeloma or Waldenstrmmacroglobulinaemia can lead to a similar problem.

Clinical manifestations of anaemia (see

Table 3)

Specific signs and symptoms of anaemia vary wideeven in patients with the same degree of anaemia. Kfactors that influence anaemic symptoms include t

Anaemia

Haemol!tic anaemias due to intrinsic RBC defects

haemoglobinopathies

sickle-cell disease (SS, SC, SB)

major and intermediate thalassaemia ( and ) RBC membrane defects

hereditary spherocytosis

RBC enzyme deficiencies

paroxysmal nocturnal haemoglobinuria

Haemol!tic anaemias due to abnormalities etrinsic to

RBCs

autoimmune haemolytic anaemia

microangiopathic haemolysis

hypersplenism

oxidative haemolysis

Table 2. Classification of haemolytic anaemias



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degree of anaemia, rapidity of its onset and co-morbiditysuch as cardiac failure. Compensatory mechanisms

often limit symptoms in anaemia with a chronic onset:slowly developing or longstanding anaemia can beasymptomatic even with surprisingly low haemoglobinlevels. Where patients are well adapted to their anaemiathere is no clinical urgency to normalise the haemoglo-bin level in older patients rapid correction of chronicanaemia by transfusion can be potentially harmful assuch an approach can result in cardiac failure.

There are no reliable clinical findings. Pallor mayoccur, and jaundice may be seen in haemolyticanaemia. Specific features in the clinical history orphysical signs may point towards a specific cause for

the anaemia. Classical signs of iron deficiency suchkoilonychia or oesophageal webs are nowadaextremely rare in UK clinical practice.

Clinical evaluation of anaemia

The physician needs to determine the likely causethe anaemia and the extent to which investigation atreatment are warranted for the individual patienfor example, in very frail or elderly patients with snificant co-morbidity invasive investigations for bloloss or other pathology are unlikely to prove beneficeither to the patient or the NHS.

A further key step in the clinical evaluation anaemia is to look at other results generated in the fblood count, specifically the white cell and platecounts. The presence of significant abnormalities m

be suggestive of, for example, drug toxicity, bone mrow pathology or an underlying autoimmune contion. Discussion of these abnormalities is beyond tscope of this article but the physician is remindedtheir relevance as part of anaemia evaluation.

The most practical approach is to base initial assement of anaemia on the MCV (see Figure 1). The mpractical second-stage diagnostically helpful tests aserum ferritin, serum vitamin B12 and folate assays (red cell folate). The use of serum iron and total irbinding capacity in the diagnosis of iron deficienshould be discouraged it is no longer reliable a

has been superseded by serum ferritin.Screening for thalassaemia trait should also be cosidered in patients with Mediterranean, AfricaMiddle Eastern or Far-Eastern ethnicity or ancestryit should also be considered where investigation donot clearly identify iron deficiency. Thalassaemia-trpatients do not benefit from iron supplementationunless they are shown to be iron deficient.

Once the likely mechanism for a given case is idetified, further referral and/or investigation shouthen be directed to find the likely underlying cauIn public health terms clear and prompt identificatiof iron deficiency in older adults represents a key st

in identification of those at risk of colorectal canceIdentification of iron-deficiency anaemia is a cle

indication that iron loss exceeds intake and, in Upractice, invariably is an indication of chronic bloloss. The clinical history will normally identify ovbleeding whether gynaecological, genitourinary gastrointestinal. Chronic GI bleeding may be undtected by the patient and missed on history taking

The British Society of Gastroenterology providguidelines on the management of iron-deficienanaemia.1 Key practice points in these guidelininclude the following statements:


Anaemia

Acute-onset anaemia

fatigue

generalised weakness

loss of stamina acute dyspnoea

syncope

Chronic anaemia

weakness, fatigue, lethargy

palpitations

dyspnoea or orthopnoea

orthostatic light-headedness

new onset or worsening of angina

new onset or worsening of claudication

Ph!sical signs

pallor of skin and mucosal surfaces

resting or orthostatic tachycardia

parasternal systolic ejection flow murmur

Vitamin B12 deficienc!

glossitis

peripheral neuropathy

combination of motor (upper and lower motor neurone

type) and sensory deficits

Haemol!tic anaemias

jaundice

splenomegaly evidence/history of splenectomy or cholecystectomy

leg ulcers

shortened digits in sickle cell disease

Iron deficienc!

angular cheilosis

glossitis

koilonychia

Table 3. Symptoms and signs of anaemias


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faecal occult blood testing is of no value to furtherinvestigation of iron-deficiency anaemia upper and lower GI investigation should be consid-ered in all postmenopausal females and all male

patients where iron-deficiency anaemia has been cofirmed unless there is a history of significant, ovnon-GI blood loss all patients should be screened for coeliac diseas


Anaemia

oral ferrous

sulphate 200mg

3 times daily

folate supple-

mentation,

specific Rx for

each symptom,

eg pain relief in

sickle cell dis-

ease

treat

inflammation,

consider EPO

EPO therapy

according to

underlying

problem

folate

supplementa-

tion, specific

Rx as per

diagnosis

im or sc

vitamin B12

often lifelong,

oral folate

replacement

Rx as per

diagnosis

complete clinical evaluation

MCV

MCV normal MCV raisedMCV, MCH low

reticulocyte count

highlow

assess iron

stores

measure serum

ferritin

test for Hb

disorderb

signs of inflam-

mation, raised

ESR or C-

reactive protein

anaemia of

chronic disease

renal failure,

primary bone

marrow dis-

ease, chronic

disease, early

Fe deficiency

haemolysis,

bleeding

assess vitamin

B12, folate,

thyroid and

liver function,

protein,

reticulocyte

count

FBC and blood film evaluationany indication for

bone marrow?a

appropriate diagnosis, plan further investigations and start treatment

Fig$!e 1. Evaluation and management of anaemia (FBC = full blood count; MCH = mean corpuscular haemoglobin; MCV = mean cell volume)

aegpancytopenia, raised MCV with normal B12, folate, etc, may signify primary bone marrow failurebwhether this is done simultaneously with requesting a ferritin level will depend on the ethnic background of the patient and/or local

haematology guidance/advice


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in patients aged >50 or with marked anaemia or asignificant family history of colorectal carcinoma,lower GI investigation should still be considered evenif coeliac disease is found

only postmenopausal women and men aged >50years should have investigation of iron deficiency with-out anaemia.

Treatment for anaemia

Iron-deficiency oral replacementThe treatment of choice for iron-deficiency anaemia isan oral preparation (see Prescribing points). The mostcost-effective approach is ferrous sulphate 200mg twicedaily, or three times daily if tolerated. Other commonlyused ferrous salts, eggluconate and fumarate, have sim-ilar rates of absorption, differing principally in the

amount of elemental iron released. Patients unable totolerate ferrous sulphate may try other ferrous salts.

Complete correction of chronic anaemia is seldomurgent. Red cell transfusion is not indicated as standardtreatment of chronically deficient patients. However,supportive transfusion of 2 units of RBCs may be helpful

where anaemic symptoms or effects are severe and needto be managed pending a response to supplementation.

Slow-release and enteric-coated preparations are pro-moted as producing fewer side-effects and requiringonce-daily administration. However, they dissolve slowlyand can bypass the proximal small bowel where most

absorption takes place. There is no evidence that theyare worth the extra cost and they may be significantly lesseffective. A poor response to therapy with slow-releaseiron cannot then be reliably interpreted clinically.

Iron absorption occurs best under conditions of lowpH in the proximal small bowel such as one hour beforemeals or at bedtime. Medication that decreases acidsecretion reduces absorption, as does food intake. GIside-effects are unfortunately common and troublesome(see Table 4). They include nausea, epigastric colic andreflux, and reflect the amount of ionised iron deliveredto the stomach and proximal small bowel. Pragmatically,because side-effects are minimised, the clinical recom-

mendation is that iron supplements are taken aftermeals. Vitamin C enhances iron absorption but is of notherapeutic value since increased absorption is generallyassociated with increased side-effects, therein reducingadherence so, for iron deficiency simple iron salts arethe mainstay and gold standard for treatment.

Lower GI side-effects are reported in about 25 percent of patients but are not necessarily a reflection ofiron dosage. Constipation usually responds to dietaryfibre or a stool softener.

Iron treatment must continue for three monthsafter normalisation of haemoglobin to replenish stores

failure to do this is a common error of omissionpractice and can lead to subsequent confusion in flow-up. It is also be the case that patients commonbecome less adherentwith continued iron supplemetation simply because they feel better and have nbeen made aware of the importance of continutreatment to replace iron stores.

Parenteral iron Parenteral preparations may be usto replenish iron stores rapidly and effectiveParenteral iron does not produce a faster haemog

bin response than adequately absorbed oral iron.In the past the risks of anaphylaxis from iron de

tran infusions limited the use of intravenous ironnewer intravenous iron preparations described belhave minimal risk. With the newer intravenous irpreparations outlined below, intramuscular admintration can no longer be clinically recommended is painful and causes permanent skin discoloration

A potential advantage of calculated intravenous irinfusions is that elements of uncertainty about admistered dosage and adherence are eliminated a fthat can be of great help in the setting of recurre


Anaemia

Iron

nausea and epigastric pain (dose related)

altered bowel habit constipation or diarrhoea

may exacerbate symptoms in inflammatory boweldisease

severe constipation (rarely leading to bowel obstructio

secondary to faecal impaction in older people)

acute overdosage nausea, vomiting, diarrhoea, GI

bleeding, hypotension and coma

acute hypersensitivity

anaphylaxis with iron dextran

painful local lymphadenopathy

flu-like symptoms

Vitamin B12 (h!droocobalamin)

rare

itching, rashes

fever, chills

hypokalaemia in severely deficient patients (needs

monitoring for the early part of the treatment)

very rare

acneform or bullous eruptions

anaphylaxis

Folate

rashes and allergic reactions

may worsen neurological symptoms or mask latent

vitamin B12 deficiency

Table 4. Side-effects of treatments for anaemia


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anaemia. There are also situations when it is helpful toreplace iron stores quickly such as before childbirth orsurgery optimising body iron stores preoperatively isalso a valuable strategy to minimise the use of donorblood in elective surgery.

Evolution in these areas of clinical practice will thuslikely result in increased use of intravenous iron for

specific clinical situations. As a principle, however, par-enteral iron should never be initiated by primary carein the absence of agreement from a relevant specialistin secondary care that it is clinically indicated.

Parenteral iron is indicated where there is docu-mented malabsorption, genuine intolerance to oralpreparations or continuing blood loss. Specific indi-cations also include iron deficiency associated withactive inflammatory bowel disease, in patients on renaldialysis (combined with erythropoietins), and in spe-cific groups with chemotherapy-induced anaemia (seeNICE Technology Appraisal 142),2 provided it is withthe exception of patients on renal dialysis.

Parenteral iron preparations available in the UKinclude the following: Iron dextran (CosmoFer) is given by slow iv infusionand carries a small risk (0.7 per cent) of anaphylaxis.It has the advantage of requiring only one or two dosesto replace iron stores. Iron sucrose complex (Venofer) has a very low inci-dence of serious adverse reactions (0.03 per cent). Thetotal dose is calculated with a standard formula. Its dis-advantage is that replacement involves a series of infu-sions, typically twice a week for one to five weeksdepending on the level of anaemia and patient weight.

Ferric carboxymaltose (Ferinject) is not associatwith severe allergic reactions and the total required docan be administered in a single, short iv infusion. Ithowever, more expensive than the other preparatio

but the fact that a single infusion may be sufficient wgo some way to offsetting the increased drug cost. Iron isomaltoside (Monofer) has recently come the market and can be administered in either a singor series of infusions. As with all iv iron preparatioit must be administered in facilities capable of proving appropriate supervision and interventions in tevent of potential anaphylactoid reactions.

Vitamin B12or cobalamin deficiencyNowadays, most patients with these deficiencies rarpresent with the classical florid manifestatio

described in textbooks; emergency treatment is thrarely required.

Initial treatment of vitamin B12 deficiency aims to crect the anaemia and resolve neurological abnormalit

where present; it will treat the deficiency and replenstores. In acute forms of presentation blood transfusishould be avoided as it risks exacerbating reversible cdiac dysfunction present in acute megaloblastic anaem

Parenteral supplementation Because the disordercaused by cobalamin malabsorption in the great majorof cases, parenteral cobalamin supplementati(hydroxocobalamin) is given intramuscularly. After inj

tion, significant amounts of the vitamin (up to 80 pcent) are excreted in the urine; therefore, initial therashould be with several large doses of cobalamin. Injectiogiven on alternate days replenish stores more rapidly thdaily injections, although there is no evidence that aone established regimen works better than others.

Patients with pernicious anaemia need lifelotherapy. Hence all younger patients should be cofirmed to have pernicious anaemia as opposed toreversible cause such as malabsorption.

It is not clear whether large or more frequent doof hydroxocobalamin are needed in patients wineurological damage. In these patients, the sam

schedule of cobalamin as detailed above is usually sficient, but longer courses are frequently given.

In severe vitamin B12 deficiency, regular moniting of serum potassium is recommended during inittherapy as hypokalaemia can occur, and potassiusupplementation is recommended for hypokalaempatients. Co-existent iron deficiency or marginal bomarrow iron stores can limit recovery and should treated with 200mg ferrous sulphate three times a d

Lifelong vitamin B12 replacement therapyrequired in pernicious anaemia, achieved by admintration of 1mg hydroxocobalamin every three mont


Anaemia

the recommended oral dose for iron deficiency is

200mg ferrous sulphate 3 times dailya

starting with a small dose of ferrous sulphate 200mg

per day and building to 600mg per day may avoid

initial intolerance

iron should generally be prescribed after meals;

although taking iron with a meal reduces absorption,

it lessens GI side-effects, such as nausea and

epigastric discomfort

to maximise adherence, patients should be advised

about the best means of minimising GI side-effects

a response is seen in 710 days with a haemoglobin

rise of approximately 20g per litre every 3 weeks

treatment needs to continue for 3 months after

normalisation of haemoglobin to replenish stores

atwice-daily dosage with ferrous sulphate or gluconate is

generally acceptable and therapeutically effective

P!e"c!ibing oin#" i!on deficienc'


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Thyroid function tests are also recommended annuallyin these patients because of an association with otherautoimmune disorders such as hypothyroidism.

Oral supplementationAn oral preparation of vitaminB12, cyanocobalamin (Cytacon), is available and is effec-tive, but requires larger doses and is significantly moreexpensive than available intramuscular forms. Such anapproach may, however, be recommended in vegetari-ans who develop dietary vitamin B12 deficiency.

Folic acid deficiencyIn contrast to vitamin B12 deficiency, folate deficiencyis usually treated with oral replacement. Folate absorp-tion occurs throughout the small intestine.Megaloblastic anaemia from folic acid deficiencyresponds readily to 5mg folic acid daily, except in sit-uations of severe malabsorption where a larger dosemay be needed. Replenishment of folate stores can beachieved within several weeks of oral therapy.

In general, maintenance therapy is not indicatedexcept in patients on long-term haemodialysis andthose with disorders of increased cellular turnover,

such as chronic haemolytic states. Such patients shoube advised about the necessity of lifelong therapy.

The clinical response in folic acid deficiencyvery similar to that seen with vitamin B12 deficien

No significant primary toxicity from folate treatmehas been reported. There is concern about the uof folate in vitamin B12-deficient patients theorecally precipitating subacute combined degeneratiof the spinal cord. While this is likely to be very rain clinical practice, it needs to be considered befoinitiating treatment. Patients taking drugs thdecrease normal folate absorption, egoral contracetives and phenytoin, may require folate supplemetation (1mg per day) if they develop evidence folate deficiency.

In any patient with nutritional deficiency, a go

understanding of the need for folate replacememust be emphasised. Patients should be educatabout foods containing the best sources of folate, suas green leafy vegetables, and about the fact that foacid is a labile vitamin and can easily be destroyed overcooking or boiling.

Folinic acid is a reduced form of folic acid thbypasses the antifolate activity of methotrexate. Iusually administered parenterally as a rescue frothe systemic antifolate effects of the drug.

Advances in anaemia treatment

EPO is produced in the kidneys and regulates RBproduction. Its gene was cloned in 1988 and recomnant forms (epoetin) became available for clinical uin 1990. EPO is now established as the standard thapy for anaemia in patients on renal dialysis (suported by folic acid supplementation and intravenoiron to overcome a functional iron deficiency) apatients with established chronic renal failure who anot on dialysis. There are NICE guidelines for its uin adult patients with haemoglobin levels


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patients. Simple, inexpensive measures, eg ironreplacement, continue to represent the only treat-ments needed for patients shown to be deficient inthese factors. Treatment in primary care must be com-

plemented by a systematic, clinically focussedapproach to anaemia evaluation to achieve optimumand timely referral for investigative procedures suchas GI endoscopy, for example, when iron-deficiencyanaemia is identified.

Indeed the British Society of Gastroenterology hassuggested some basic quality standards for iron defi-ciency : all patients with iron-deficiency anaemia should bescreened for coeliac disease all patients (other than menstruating women) withiron-deficiency anaemia and no obvious cause should

have both an upper GI endoscopy and eithercolonoscopy or radiological imaging (unless carci-noma or coeliac disease is found) all patients receive appropriate iron replacement all those not responding to treatment should be con-sidered for further investigation in all patients being investigated for iron-deficiencyanaemia, reasonable evidence of iron-deficiencyanaemia should be documented by appropriate Hb,MCH and MCV or ferritin values, or there should bean explanation of why iron deficiency is suspected inpatients not showing typical blood test results.

These form a useful template for audit in primarycare particularly in relation to the common prob-lem of iron deficiency. They focus on the importance

of simple diagnostic tests available to primary carecoupled with systematic clinical assessment to deter-mine the appropriate next steps in further investi-gation.

Anaemia is a common finding in practice. A sys-tematic approach to determining the likely cause is acore skill in primary care; the finding of anaemia andits significance for the individual patient combine todetermine the next stages and extent of further inves-tigation getting this process right has profound impli-cations for the cost-effectiveness and management ofNHS resources. The approach outlined in this reviewaims to equip the busy primary care clinician with theskills to achieve this objective.

References

1. Goddard AF, et al, on behalf of the British Society ofGastroenterology. Gut2011;60:130916.2. NICE.Epoetin alfa, epoetin beta and darbepoetin alfa for cancertreatment-induced anaemia. Technology appraisal 142. May2008.3. NICE. Anaemia management in people with chronic kidney dis-ease. Clinical guideline 114. February 2011.

Declaration of interests

None to declare.

Dr Smith is an honorary consultant haematologist atUniversity Hospital Southampton NHS Trust and a

national clinical advisor to the National CancerSurvivorship Initiative; he is also a clinical advisor toMacmillan Cancer Support and Myeloma UK

www.prescriber.co.uk Prescriber 5 November 2012 41

Anaemi

Prescription reviewSpending on oral iron products in 2011 decreased fromabout 16.5 million in 2010 to 13.4 million despite aslight increase in volume to 6.7 million scrips. GPs inEngland still preferred ferrous sulphate (50 per cent ofmarket share, 54 per cent of costs) to ferrous fumarate

(41 and 26 per cent respectively) or ferrous gluconate(5 and 13 per cent). Ferrous sulphate prescribing wasdominated by the generic 200mg tablet whereas onlybrands of the fumarate are available, with Fersamal210mg tablets accounting for 78 per cent of scrips. Of the liquid formulations, sodium feredetate(Sytron Elixir) was the most popular, followed byGalfer syrup (54 000 scrips). There were few scrips forferrous sulphate solution specials but the cost of each

was high, ranging from 180 to 290. Iron dextran (CosmoFer) accounted for most pri-mary care prescribing of parenteral iron products and

fewer than 1 in 15 scrips were for iron sucrose (Veno-fer). Cyanocobalamin was overwhelmingly prescribedas generic 50g tablets.

Table 5. Number, total cost and average cost per scrip of pre-

scriptions for anaemia in England, 2011

ferrous fumarate 2 762 3 495 1.27

iron + folic acid 116 229 1.98

ferrous sulphate 3 346 7 307 2.18

iron feredetate 156 500 3.21

ferrous gluconate 340 1 749 5.15

cyanocobalamin 369 2 691 7.29

parenteral iron 2.9 100 35.00

I#em" Co"# Co"# e!

(000") (000") "c!i ()


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Anaemia


1. One of these statements is false which is it?

a. In Western populations, anaemia is considered to be presentwhen the haemoglobin level is less than 110g per litre inmales and 105g per litre in females

b. Mean cell volume (MCV) is used to classify anaemia and thusdetermine further investigation and management

c. The normal range for MCV is 7898fl

d. Anaemia may be caused by an impaired ability of the bonemarrow to produce sufficient numbers of red blood cellsand/or accelerated destruction or loss of red blood cells

2. Which one of these statements about the pathogenesis of

anaemia is false?

a. Hypochromic microcytic anaemia arises from impairedhaemoglobin synthesis and is a result of reduced produc-tion of either haem or globin

b. Chronic infectious or inflammatory diseases can causeanaemia by impairing the utilisation of available iron

c. Megaloblastic anaemia is a macrocytic anaemia associatedwith varying degrees of anaemia

d. Excess alcohol intake causes macrocytic anaemia that is nor-mally associated with profound anaemia

3. One of these statements is false which?

a. MCV is always reduced in haemolytic anaemia

b. The most important cause of acute-onset normocyticanaemia is acute blood loss

c. Serum bilirubin levels are often, but not always, raised Inhaemolytic anaemias

d. In pregnancy, haemoglobin can fall as low as about 100gper litre but no treatment is required

4. Which one of these statements about the manifestation

and clinical evaluation of anaemia is false?

a. Anaemia may be associated with a systolic ejection flow murm

b. Haemolytic anaemia may be associated with leg ulcers

c. Total iron binding capacity is an essential measurement inthe diagnosis of iron-deficiency anaemia

d. All patients with iron-deficiency anaemia should bescreened for coeliac disease

5. Which one of these statements about the treatment of

anaemia is false?

a. The most cost-effective treatment for iron-deficiencyanaemia is ferrous sulphate 200mg twice or three times da

b. It is clinically recommended that iron supplements aretaken after meals because this maximises absorption

c. Vitamin C enhances iron absorption but is of no therapeutvalue because increased absorption generally increasesside-effects and therefore reduces adherence

d. Oral iron treatment must continue for three months afternormalisation of haemoglobin

6. One of these statements is false which is it?

a. Parenteral iron is indicated for patients with anaemia whethere is documented malabsorption, genuine intoleranceoral preparations or continuing blood loss

b. The total required dose of iron can be administered as a sigle iv infusion of ferric carboxymaltose.

c. In patients with vitamin B12 deficiency, injections ofhydroxocobalamin should be initiated at a low dose andslowly titrated up over a six-week period

d. Vitamin B12 deficiency should be excluded before startingfolate supplementation

Anaemia

CPD: AnaemiaAnswer these questions online at Prescriber.co.uk and receive acertificate of completion for your CPD portfolio. Utilise theLearning into Practice form to record how your learning hascontributed to your professional development.

ResourcesGuidelinesGuidelines for the diagnosis and management of aplasticanaemia. British Committee for Standards inHaematology, April 2009.

Guidelines for the management of iron deficiency anaemia.British Society of Gastroenterology, March 2011.

UK guidelines on the management of iron deficiency in preg-nancy. British Committee for Standards inHaematology, July 2011.

Groups and organisationsThe British Society for Haematology, 100 WhLion Street, London N1 9PF. Tel: 020 7713 099

website: www.b-s-h.org.uk. Publishes various guidlines for clinicians and also the British JournalHaematology.

Aplastic Anaemia Trust, PO Box 2821, Romford, RM1GL. Tel: 0870 487 7778, website: www.theaat.org.uSupports patients with aplastic anaemia and allied dorders.

Anemia Manejo

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