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Anaemia - assessment and classification Medicine > Haematology and haemostasis > Anaemia Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinical information. Page 1 of 14 Background information Updates to this care map Key recommendations of the care map - 1 Abbreviations used in this care map Key recommendations of the care map - 2 Aetiology Clinical presentation Initial assessment and investigations Further investigation and diagnosis Go to Megaloblastic anaemias - management Vitamin B12 deficiency Refer to haematologist Go to Common haemoglobinopathies Go to chronic anaemias Folate deficiency anaemia Megaloblastic anaemia Myelodysplastic disorders Thalassemia Iron deficiency anaemia Normal MCV Low MCV Determine underlying cause High MCV Low iron, normal/high TIBC and normal/low ferritin Low iron, any TIBC, and normal/ high ferritin Iron overload and sideroblasts on peripheral film Low vitamin B12 and elevated methylamlonate Low folate and normal methylmalonate Other causes of anaemia Request iron profile and ferritin Teardrop or target cells, splenomegaly and family history Condsider referral to haematology Low Hb on CBC Go to autoimmune and aplastic anaemia Anaemia of chronic disease Autoimmune haemolytic anaemias Other causes - treat accordingly Go to chronic anaemias Sideroblastic anaemia Low iron, normal/low TIBC, and normal/high ferritin Anaemia of chronic disease Go to chronic anaemias

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Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 1 of 14

Backgroundinformation

Updates to this caremap

Key recommendations

of the care map − 1

Abbreviations used inthis care map

Key recommendations

of the care map − 2

Aetiology

Clinical presentation

Initial assessment andinvestigations

Further investigationand diagnosis

Go to Megaloblasticanaemias -management

Vitamin B12 deficiency

Refer to haematologist

Go to Commonhaemoglobinopathies

Go to chronicanaemias

Folate deficiencyanaemia

Megaloblastic anaemia

Myelodysplasticdisorders

Thalassemia

Iron deficiencyanaemia

Normal MCVLow MCV

Determine underlyingcause

High MCV

Low iron,normal/high TIBC andnormal/low ferritin

Low iron,any TIBC, and normal/high ferritin

Iron overload andsideroblasts onperipheral film

Low vitamin B12and elevatedmethylamlonate

Low folate and normalmethylmalonate

Other causes ofanaemia

Request iron profileand ferritin

Teardrop or targetcells, splenomegalyand family history

Condsider referral tohaematology

Low Hb on CBC

Go to autoimmune andaplastic anaemia

Anaemia of chronicdisease

Autoimmunehaemolytic anaemias

Other causes - treataccordingly

Go to chronicanaemias

Sideroblastic anaemia

Low iron,normal/low TIBC, andnormal/high ferritin

Anaemia of chronicdisease

Go to chronicanaemias

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 2 of 14

1 Background information

Quick info:The purpose of this care map is to define the appropriate diagnosis and management of common anaemias presenting in adults.The objective is to improve the appropriateness of investigation, prescribing, and referral of patients presenting to providerorganisations in Qatar. It is intended that the care map will be used primarily by physicians in primary care and outpatient settings.Scope of the care map Aspects of care covered in this care map include the following:

• Diagnosis and management of common anaemias in adults, including:

• Iron deficiency anaemia.

• Thalassaemia.

• Sickle cell haemoglobinopathies.

• Aplastic anaemia.

• Anaemia of chronic disease.

• Autoimmune haemolytic anaemias.

• Megaloblastic anaemias.

Aspects of care not covered in this care map are:

• Anaemia in children.

• Sideroblastic anaemias.

• Non-autoimmune haemolytic anaemias.

• Detailed discussion of myelodysplastic disorders.

DefinitionsAnaemia is not a diagnosis and requires a full diagnostic evaluation aimed at establishing the underlying cause [1].Anaemia is defined as [2]:

• A condition in which the quality and/or quantity of circulating red blood cells are below normal.

• Hb levels [3]:

• <13 g/dL (130 g/L) in male patients.

• <12 g/dL (120 g/L) in female patients.

• <11 g/dL (110 g/L) in pregnant women.

Anaemia is typically classified on a morphological basis according to the size of erythrocytes, into the following categories [1]:

• Microcytic (MCV: <80 fL).

• Normocytic (MCV: 80-100 fL).

• Macrocytic (MCV: >100 fL).

EpidemiologyDefinitive data on the incidence and prevalence of anaemia in Qatar is not presently available. However, the 2011 WHO-estimatedpercentages of women with anaemia were as follows [16]:

• Non-pregnant women aged 15-49 years:

• Hb <12 g/dL (<120 g/L): 28

• Hb <8 g/dL (<80 g/L): 0.7%.

• Pregnant women aged 15-49 years:

• Hb <11 g/dL (<110 g/L): 28%.

• Hb <7 g/dL (<70 g/L): 0.2%.

Approximately 50% of anaemia in women world-wide is due to iron deficiency. In parts of the Eastern Mediterranean and MiddleEast, inherited anaemias (including sickle cell traits, G6PD deficiency and thalassaemias) are important causes of anaemia toconsider [16].References:Please see the care map's Provenance.

2 Aetiology

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 3 of 14

Quick info:Microcytic anaemiaCauses of microcytic anaemia include:

• Iron deficiency anaemia, resulting from [4-8]:

• Chronic blood loss including:

• Menorrhagia.

• Epistaxis.

• Haematuria.

• Upper GI bleeding.

• Lower GI bleeding.

• Dietary deficiency.

• Malabsorption of iron, e.g.:

• Gastric surgery, coeliac disease, or extensive bowel resection.

• Increased demand for iron, e.g.:

• Pregnancy.

• Anaemia of chronic disease, resulting from [1]:

• Chronic infection, e.g.:

• Tuberculosis.

• Chronic inflammation, including:

• Rheumatoid arthritis

• Systemic lupus erythematosus.

• Polymyalgia rheumatica.

• Malignancy.

• Sideroblastic anaemia, resulting from [1]:

• Inherited disease:

• X-linked inheritance.

• Acquired disease:

• Myelodysplasia.

• Myeloproliferative disorders.

• Myeloid leukaemia.

• Rheumatoid arthritis.

• Malignancy.

• Drugs e.g., isoniazid.

• Alcohol misuse.

• Lead toxicity.

• Thalassaemias [1].

Normocytic anaemiaNormocytic anaemia may result from [9]:

• Increased red blood cell loss or destruction.

• Decreased red cell production.

Causes of normocytic anaemia due to increased RBC loss or destruction include [1,9-12]:

• Acute blood loss.

• Hypersplenism.

• Haemolytic disorders:

• Congenital conditions:

• Haemoglobinopathies, e.g. homozygous sickle cell disease (haemoglobin SS disease); heterozygous sickle haemoglobinC disease (haemoglobin SC disease).

• Disorders of red cell membranes, e.g. hereditary spherocytosis, hereditary elliptocytosis.

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 4 of 14

• Red blood cell enzyme deficiencies, e.g. glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency.

• Mechanical haemolysis:

• Macrovascular disorders, e.g. history of heart valve replacement or valvular disorder.

• Microangiopathic disorders, e.g. disseminated intravascular coagulopathy, haemolytic-uraemic syndrome, thromboticthrombocytopenic purpura.

• Autoimmune haemolytic anaemias:

• Warm-reactive anaemias.

• Cold-reactive anaemias.

• Drug-induced anaemias.

• Paroxysmal nocturnal haemoglobinuria.

• Drugs that can cause haemolysis, e.g.:

• Penicillin.

• Methyldopa.

• Cephalosporins.

• Erythromycin.

• Procainamide.

• Paracetamol.

• Infections.

• Blood transfusion reactions.

Causes of normocytic anaemia due to decreased red cell production may include [1,2,9,10,13,14]:

• Primary causes:

• Marrow aplasia or hypoplasia.

• Pure red blood cell aplasia.

• Myelopathies.

• Myeloproliferative disorders.

• Secondary causes:

• Chronic renal failure.

• Liver disease.

• Endocrine deficiencies.

• Inflammatory disorders.

• Infections.

• Cancer.

• HIV.

• Drugs:

• Antiepileptic medications.

• Azathioprine.

• Sulphonamides.

• Isoniazid.

• Procainamide.

• Penicillamine.

• Chloramphenicol.

• Expansion of plasma volume:

• Pregnancy.

• Over-hydration.

Macrocytic anaemiaCommon causes of macrocytic anaemia include [1,9,14,15]:

• Vitamin B12 or folate deficiency.

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 5 of 14

• Excess alcohol intake − may cause macrocytosis more commonly due to toxic effect of alcohol than folate deficiency secondaryto alcoholism.

• Pregnancy and the neonatal period.

• Drugs, e.g.:

• Azathioprine.

• Hydroxycarbamide.

• Methotrexate.

• Anticonvulsants (phenytoin, valproic acid).

• Trimethoprim/sulfamethoxazole.

• Metformin.

• Cholestyramine.

• Zidovudine.

• Stavudine.

• Lamivudine.

• Hypothyroidism – modest increase in mean cell volume may be seen.

• Liver disease (non-alcoholic).

• Haemolysis.

Rarer causes include [1,13,15]:

• Myeloma.

• Myelofibrosis.

• Myelodysplastic syndrome.

• Bone marrow failure syndromes, e.g. aplastic anaemia, red cell aplasia.

• Primary bone marrow dysplasias including myelodysplasia and myeloproliferative disorders.

References:Please see the care map's Provenance.

3 Updates to this care map

Quick info:Date of publication: 19-Mar-2017Please see the care map's Provenance for additioal information on references, contributors, and the editorial approach.

4 Key recommendations of the care map − 1

Quick info:The key recommendations of this care map are:Diagnosis:

• Anaemia is not a diagnosis and requires a full diagnostic evaluation aimed at establishing the underlying cause [1].

• Approximately 50% of anaemia in women world-wide is due to iron deficiency.

• In parts of the Eastern Mediterranean and Middle East, inherited anaemias (including sickle cell traits, G6PD deficiency andthalassaemias) are important causes of anaemia to consider [16].

Initial investigation:

• CBC with differential [1,3,26].

• Consider performing a peripheral blood film if [1,4,26][R-GDG]:

• Anaemia is confirmed on CBC and;

• Iron deficiency anaemia is not suspected.

IDA:

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 6 of 14

• Perform further investigations relevant to the underlying cause and according to the clinical scenario for confirmed IDA (see theAetiology' care point).

• Unless significant overt non-GI loss is present, all postmenopausal women and male patients with confirmed IDA should bereferred for an upper and lower GI investigation [4][L2, RGA1].

• The underlying cause of the IDA should be investigated and documented appropriately [R-GDG].

• In patients with a treatable underlying cause continue iron supplementation until the Hb concentration and red cell indices arenormal [4,7]:

• Continue oral iron for 3 further months until iron stores are replenished and then stop.

• Monitor Hb levels and red cell indices every 3 months for one year [4,7][L3, RGA2].

• Recheck Hb levels once more after another year has passed and if symptoms recur.

• If Hb or red cell indices drop below normal, give additional iron.

• Further investigations are only indicated if Hb and red cell levels have not normalised despite treatment.

IDA in pregnancy:

• Women with Hb <11 g/dL (<110 g/L) before 12 weeks’ gestation or <10.5 g/dL (<105 g/L) beyond 12 weeks gestation, areanaemic and should be offered a trial of therapeutic iron replacement – unless they are known to have a haemoglobinopathy[8].

• Severely anaemic pregnant patients, i.e. Hb levels <7 g/dL (<70 g/L) patients should be referred urgently to an obstetricspecialist [8].

Thalassaemia:

• In thalassaemia minor: The Hb electrophoresis may be normal, if a combined iron deficiency is present. Therefore, it isimportant to treat any suspected iron deficiency, prior to testing for thalassaemia [R-GDG].

• Refer all patients to a haematologist if thalassaemia intermedia or major are suspected or confirmed [R-GDG].

Sickle cell haemoglobinopathies:

• When sickling crises are suspected, prompt and efficient treatment remains vital and primarily consists of [31]:

• Pain relief.

• Oxygenation.

• Hydration.

• Treatment of bacterial infection or the underlying cause.

• Transfusion may be considered after discussion with a haematologist.

Aplastic anaemia (AA):

• AA is defined as a pancytopenia (Hb <10 g/dL, platelet count <50 x109/L, neutrophil count <1.5 x 109/L), with a hypocellularbone marrow in the absence of an abnormal infiltrate or marrow fibrosis [33].

• See 'Autoimmune and aplastic anaemia - management' for the initial investigations to be performed in cases of suspected AA.

• Refer all patients with suspected AA to a haematologist after exclusion of other common causes of anaemia [R-GDG].

Myelodysplatic syndrome (MDS):

• MDS may be indicated by the following [35,36]:

• Usually an elderly patient with macrocytic anaemia.

• Features of dysplasia on peripheral smear.

• Unexplained cytopenia.

• If MDS is suspected refer all cases to a haematologist for further management [R-GDG].

ACD:

• ACD is a common cause of anaemia and is frequently associated with chronic infection or inflammatory disease states [1,9,37].

• Patients with ACD should be referred to an appropriate specialist for management of the underlying cause [R-GDG].

References:Please see the care map's Provenance.

5 Key recommendations of the care map − 2

Quick info:

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 7 of 14

Autoimmune haemolytic anaemias:

• Autoimmune haemolytic anaemias are typically indicated by [1,12]:

• High MCV.

• Reticulocytosis.

• NB: MCV and reticulocytes may be normal in the early stages of the disease.

• Positive Coomb’s test (DAT).

• If autoimmune haemolytic anaemia is suspected on initial investigations refer to a haematologist for further management [R-GDG].

• All patients with a suspected acute haemolytic crisis should however be referred to the emergency department [R-GDG].

Vitamin B12 deficiency:

• Vitamin B12 deficiency is indicated by [1,38]:

• Very high MCV.

• Low serum vitamin B12 level.

• Elevated methylmalonate level.

• May be associated with pancytopenia.

• Investigations of vitamin B12 deficiency include [38,41]:

• Testing for serum anti-intrinsic factor antibodies [38,41][L2, RGA1].

• A positive test is associated with a high likelihood of pernicious anaemia.

• See 'Autoimmune and aplastic anaemia' for treatment and maintenance therapy in vitamin B12 deficiency.

• Consider seeking specialist advice from an appropriate specialist if:

• A myelodysplastic syndrome is suspected [R-GDG].

• A second opinion is required [R-GDG].

• Malabsorption of vitamin B12, other than pernicious anaemia, is suspected [38].

• Patient has pernicious anaemia and gastrointestinal symptoms [38].

• Vitamin B12 deficiency is thought to be due to poor diet [38].

Folate deficiency:

• Folate deficiency is commonly seen in [6,8,10,20,38,39]:

• Patients with poor dietary intake of natural sources of folate (e.g. legumes, chickpeas, and brown rice).

• Certain gastrointestinal conditions (coeliac disease, inflammatory bowel disease).

• Blood disorders (e.g. haemolytic anaemia).

• Pregnancy.

• Folate requirement is increased during pregnancy.

• Chronic alcoholism.

• Use of anticonvulsant drugs or trimethoprim.

• See 'Megaloblastic anaemia - management' for the management of folate deficiency.

References:Please see the care map's Provenance.

6 Abbreviations used in this care map

Quick info:The abbreviations used in this care map are as follows:AAAplastic anaemiaACDAnaemia of chronic diseaseANAAnti-nuclear antibodies

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 8 of 14

CBCComplete blood countCMVCytomegalovirusDATDirect antiglobulin testDsDNADouble-stranded DNAEBVEpstein-Barr virusESAErythropoiesis-stimulating agentsG6PDGlucose-6-phosphate dehydrogenaseGIGastrointestinalGORDGastro-oesophageal reflux diseaseHbHaemoglobinHbANormal adult haemoglobinHbASHeterozygous combination of the normal haemoglobin gene with the sickle cell geneHbSSickle haemoglobinHbSBHeterozygous combination of abnormal haemoglobin genes with the sickle cell geneHbSSHomozygous sickle cell geneHIVHuman immunodeficiency virusHRTHormone replacement therapyIDAIron deficiency anaemiaIMIntramuscular routeLDHLactate dehydrogenaseMCHMean corpuscular haemoglobinMCHCMean corpuscular haemoglobin concentrationMCVMean corpuscular volumeMDSMyelodysplastic syndromeNSAIDSNon-steroidal anti-inflammatory drugsPPIProton pump inhibitorPR

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 9 of 14

Per rectumRBCRed blood cellTIBCTotal iron-binding capacityReferences:Please see the care map's Provenance.

7 Clinical presentation

Quick info:Presenting features are common to most anaemias [2,8,11,13,17,18]:

• Common symptoms:

• Fatigue, lethargy, weakness.

• Shortness of breath.

• Palpitations.

• Headache.

• Lightheadedness or dizziness.

• Less common symptoms:

• Tinnitus.

• Taste disturbance.

• Pruritus.

• Pica: Abnormal cravings for non-food items, e.g. ice, sand, paint, or starch.

• Sore tongue.

• Brittle nails.

• Hair loss.

• Restless legs syndrome.

References:Please see the care map's Provenance.

8 Initial assessment and investigations

Quick info:Consider asking about the following:

• Dietary history [4,7,19,20][L1]:

• Vegans and vegetarians or patients on other restricted diets.

• Alcohol intake.

• GI ulceration/bleeding [1,4,7,21,22][L1]:

• NSAIDs, aspirin, corticosteroid or anticoagulant use.

• Dyspepsia, GORD, history of peptic ulcer.

• Haemorrhoids.

• Passing blood PR.

• Passing black motions, confirm they are not taking iron tablets.

• Personal or family history of:

• Telangiectasia or angiodysplasia.

• Coagulopathies.

• Inflammatory bowel disease.

• Malabsorption [4,6][L2]:

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 10 of 14

• History of GI diseases, gastrectomy, or bariatric surgery.

• Symptoms including: indigestion, diarrhoea, steatorrhoea, abdominal distention.

• Menstrual history [1,13]:

• Frequency, duration, estimated blood loss.

• Obstetric history.

• Post-menopausal bleeding.

• Haematuria [5,7].

• Epistaxis [4,7].

• Parasitic infestations [23].

Consider performing a general physical examination, as directed by the clinical presentation. Features to examine for include[1,4,7,18,24,25,26]:

• Assess pallor of conjunctivae, mucus membranes and palms.

• Assess for:

• Stomatitis and cheilitis.

• Atrophic glossitis.

• Nail changes − brittle, ridged koilonychia.

• Look for cutaneous signs such as jaundice, petechiae, bruising, telangiectasia, or rare causes of GI blood loss, e.g. Peutz-Jeghers syndrome and hereditary haemorrhagic telangiectasia [1,4,11,27].

• Cardiovascular examination:

• Signs of heart failure, infective endocarditis, prosthetic heart valves, tachycardia, postural hypotension.

• Neurological examination:

• Signs of peripheral neuropathy or cognitive impairment.

• Rectal examination:

• PR bleeding, melaena, rectal masses, haemorrhoids.

Initial investigations for anaemia [1,3,26]:

• CBC with differential.

Consider performing a peripheral blood film if [1,4,26][R-GDG]:

• Anaemia is confirmed on CBC; and

• Iron deficiency anaemia is not suspected.

References:Please see the care map's Provenance.

9 Low Hb on CBC

Quick info:Assess MCV and consider a peripheral blood film [1,4,26].References:Please see the care map's Provenance.

14 Further investigation and diagnosis

Quick info:Further investigation required, possible causes include [1,4,26]:

• Acute blood loss.

• Haemolytic anaemia.

• Bone marrow suppression.

• Combined nutritional deficiency.

• Anaemia of chronic disease.

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 11 of 14

References:Please see the care map's Provenance.

17 Myelodysplastic disorders

Quick info:MDS may be indicated by the following [35,36]:

• Usually an elderly patient with macrocytic anaemia.

• Features of dysplasia on peripheral smear.

• Unexplained cytopenia.

NB: If MDS is suspected refer all cases to a haematologist for further management [R-GDG].References:Please see the care map's Provenance.

18 Other causes of anaemia

Quick info:Other causes of anaemia include [1,4,26}:

• Drug induced.

• Hypothyroidism.

• Haemolysis.

• Liver disease.

• Increased reticulocytes.

References:Please see the care map's Provenance.

24 Condsider referral to haematology

Quick info:Determine underlying cause and coonsider referral to haematology [1,4,26].References:Please see the care map's Provenance.

25 Megaloblastic anaemia

Quick info:If suspected, the following investigations should be performed in addition to a CBC and a peripheral smear [15]:

• Reticulocyte count.

• LDH.

• Methylmalonate level.

• Homocysteine.

• Vitamin B12.

• Red cell folate level.

References:Please see the care map's Provenance.

26 Anaemia of chronic disease

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 12 of 14

Quick info:Anaemia of chronic disease is indicated by [1,9,37]:

• Low or normal MCV.

• Low serum iron.

• Normal or low TIBC.

• Normal or elevated serum ferritin.

References:Please see the care map's Provenance.

27 Autoimmune haemolytic anaemias

Quick info:Autoimmune haemolytic anaemias are typically indicated by [1,12]:

• High MCV.

• Reticulocytosis.

• NB: MCV and reticulocytes may be normal in the early stages of the disease.

• Positive Coomb’s test DAT.

Other findings that may be present include [1,12]:

• Splenomegaly.

• Abnormal red cells on peripheral smear:

• Spherocytosis.

• Polychromasia.

• Anisopoikilocytosis.

• Raised LDH.

• Raised indirect bilirubin with normal ALT.

• Low haptoglobin.

References:Please see the care map's Provenance.

28 Other causes - treat accordingly

Quick info:Other possible causes include [1,4,26]:

• Acute blood loss.

• Bone marrow suppression.

• Combined nutritional deficiency.

References:Please see the care map's Provenance.

29 Iron deficiency anaemia

Quick info:Iron deficiency anaemia is indicated by [1,4,7,13,26]:

• Low MCV (<80 fL).

• Low MCH and low MCHC.

• Microcytic hypochromic red cells on peripheral blood film.

• Low serum iron.

• High TIBC.

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 13 of 14

• Low ferritin.

References:Please see the care map's Provenance.

33 Vitamin B12 deficiency

Quick info:Vitamin B12 deficiency is indicated by [1,38]:

• Very high MCV.

• Low serum vitamin B12 level.

• Elevated methylmalonate level

• May be associated with pancytopenia.

References:Please see the care map's Provenance.

34 Folate deficiency anaemia

Quick info:Folate deficiency is indicated by [1,20,38]:

• Very high MCV.

• Low folate levels.

• Normal methylmalonate levels.

Folate deficiency is commonly seen in [6,8,10,20,38,39]:

• Patients with poor dietary intake of natural sources of folate (e.g. legumes, chickpeas, and brown rice).

• Certain gastrointestinal conditions (coeliac disease, inflammatory bowel disease).

• Blood disorders (e.g. haemolytic anaemia).

• Pregnancy:

• Folate requirement is increased during pregnancy.

• Chronic alcoholism.

• Use of anticonvulsant drugs or trimethoprim.

References:Please see the care map's Provenance.

35 Sideroblastic anaemia

Quick info:NB: The care of sideroblastic anaemia is not within the scope of this care map.References:Please see the care map's Provenance.

36 Thalassemia

Quick info:Thalassaemias are indicated by [1,4,7,26]:

• Low MCV (<80 fL).

• Teardrop red cells on peripheral blood film.

• Target cells.

• Splenomegaly may be present.

Anaemia - assessment and classificationMedicine > Haematology and haemostasis > Anaemia

Published: 20-Mar-2017 Valid until: 31-Mar-2019 Printed on: 30-Oct-2017 © Map of Medicine Ltd This care map was published by Qatar. A printed version of this document is not controlled so may not be up-to-date with the latest clinicalinformation.

Page 14 of 14

• Positive family history may be present.

References:Please see the care map's Provenance.

Anaemia

___________________________________________________________________________________________

Provenance Certificate

Overview Editorial

approach Evidence Grading References

Guideline Development Group

Responsibilities Acknowledgements

Overview

This guideline document has been developed and issued by the Ministry of Public Health of Qatar (MOPH), through a process

which aligns with international best practice in guideline development and localisation. The guideline will be reviewed on a

regular basis and updated to incorporate comments and feedback from stakeholders across Qatar.

Whilst the MOPH has sponsored the development of the care map, the MOPH has not influenced the specific recommendations

made within it.

This care map was approved on 19 Mar 2017.

For information on changes in the last update, see the information point entitled 'Updates to this care map' on each page of the

care map.

Editorial approach

This care map has been developed and issued by the Ministry of Public Health of Qatar (MOPH), through a process which

aligns with international best practice in guideline development and localisation. The care map will be reviewed on a regular

basis and updated to incorporate comments and feedback from stakeholders across Qatar.

The editorial methodology, used to develop this care map, has involved the following critical steps:

Extensive literature search for well reputed published evidence relating to the topic.

Critical appraisal of the literature.

Development of a draft summary guideline.

Review of the summary guideline with a Guideline Development Group, comprised of practising physicians and subject

matter experts from across provider organisations in Qatar.

Independent review of the guideline by the Clinical Governance body appointed by the MOPH, from amongst

stakeholder organisations across Qatar.

Explicit review of the care map by patient groups was not undertaken.

Whilst the MOPH has sponsored the development of the care map, the MOPH has not influenced the specific

recommendations made within it.

Sources of evidence

The professional literature published in the English language has been systematically queried using specially developed,

customised, and tested search strings. Search strategies are developed to allow efficient yet comprehensive analysis of relevant

publications for a given topic and to maximise retrieval of articles with certain desired characteristics pertinent to a guideline.

For each guideline, all retrieved publications have been individually reviewed by a clinical editor and assessed in terms of

quality, utility, and relevance. Preference is given to publications that:

1. Are designed with rigorous scientific methodology.

2. Are published in higher-quality journals (i.e. journals that are read and cited most often within their field).

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3. Address an aspect of specific importance to the guideline in question.

Where included, the ‘goal length of stay’ stated within this guideline is supported by and validated through utilisation analysis of

various international health insurance databases. The purpose of database analysis is to confirm the reasonability and clinical

appropriateness of the goal, as an achievable benchmark for optimal duration of inpatient admission.

Evidence grading and recommendations

Recommendations made within this guideline are supported by evidence from the medical literature and where possible the

most authoritative sources have been used in the development of this guideline. In order to provide insight into the evidence

basis for each recommendation, the following evidence hierarchy has been used to grade the level of authoritativeness of the

evidence used, where recommendations have been made within this guideline.

Where the recommendations of international guidelines have been adopted, the evidence grading is assigned to the underlying

evidence used by the international guideline. Where more than one source has been cited, the evidence grading relates to the

highest level of evidence cited:

Level 1 (L1):

o Meta-analyses.

o Randomised controlled trials with meta-analysis.

o Randomised controlled trials.

o Systematic reviews.

Level 2 (L2):

o Observational studies, examples include:

Cohort studies with statistical adjustment for potential confounders.

Cohort studies without adjustment.

Case series with historical or literature controls.

Uncontrolled case series.

o Statements in published articles or textbooks.

Level 3 (L3):

o Expert opinion. o Unpublished data, examples include:

Large database analyses. Written protocols or outcomes reports from large practices.

In order to give additional insight into the reasoning underlying certain recommendations and the strength of recommendation,

the following recommendation grading has been used, where recommendations are made:

Recommendation Grade A1 (RGA1): Evidence demonstrates at least moderate certainty of at least moderate net

benefit.

Recommendation Grade A2 (RGA2): Evidence demonstrates a net benefit, but of less than moderate certainty, and

may consist of a consensus opinion of experts, case studies, and common standard care.

Recommendation Grade B (RGB): Evidence is insufficient, conflicting, or poor and demonstrates an incomplete

assessment of net benefit vs harm; additional research is recommended.

Recommendation Grade C1 (RGC1): Evidence demonstrates a lack of net benefit; additional research is

recommended.

Recommendation Grade C2 (RGC2): Evidence demonstrates potential harm that outweighs benefit; additional

research is recommended.

Recommendation of the GDG (R-GDG): Recommended best practice on the basis of the clinical experience of the

Guideline Development Group members.

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References

1. Woolf N. Pathology: Basic and Systemic. 1st Edn, London: Saunders, 1998.

2. National Institute for Health and Clinical Excellence (NICE). Chronic Kidney Disease: Managing anaemia. NICE guideline NG8. London: NICE; 2015.

3. World Health Organization (WHO). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization; 2011.

4. Goddard AF, James MW, McIntyre AS, et al. Guidelines for the management of iron deficiency anaemia. GUT 2011; 60:1309-1316.

5. National Collaborating Centre for Cancer (NCC-C). Suspected cancer: recognition and referral. NICE guideline NG12. London: NCC-C; 2015.

6. Internal Clinical Guidelines Team (ICGT). Coeliac disease: recognition, assessment and management. NICE guideline NG20. London: ICGT; 2015.

7. Short MW, Domagalski JE. Iron deficiency anaemia: evaluation and management. Am Fam Physician 2013; 87:98-104.

8. Pavord S, Myers B, Robinson S et al. UK guidelines on the management of iron deficiency in pregnancy. Br J haematol 2012; 156:588-600.

9. Brill JR, Baumgardner DJ. Normocytic anemia. Am Fam Physician 2000; 15: 2255-64.

10. Roy CN. Anemia of inflammation. Hematology Am Soc Hematol Educ Program 2010; 2010: 276-80.

11. Hill QA, Stamps R, Massey E. The diagnosis and management of primary autoimmune haemolytic anaemia. London: British Society for Haematology; 2016.

12. Lichtin AE. MSD Manual Professional Version. Overview of haemolytic anaemia [Internet]. Kenilworth, NJ: MSD Manuals; [accessed 04 September 2016]. http://www.msdmanuals.com/en-gb/professional/hematology-and-oncology/anemias-caused-by-hemolysis/overview-of-hemolytic-anemia.

13. Zaiden R, Rana F. Assessment of anaemia. Best Practice. London: BMJ Publishing Group Ltd; 2011.

14. British National Formulary (BNF). BNF June 2016. London: BMJ Group and RPS Publishing; 2016.

15. Kaferle J, Strzoda CE. Evaluation of macrocytosis. Am Fam Physician 2009; 79: 203-8.

16. World Health Organization (WHO). The global prevalence of anaemia in 2011. Geneva, Switzerland: WHO; 2015.

17. Crummer RW, Hassan GA. Diagnostic approach to tinnitus. Am Fam Physician 2004; 69:120-6.

18. National Heart Lung and Blood Institute (NHLBI). Signs and symptoms of iron-deficiency anemia [Internet]. Bethesda, MD: NHLBI;[accessed 02 September 2016]. https://www.nhlbi.nih.gov/health/health-topics/topics/ida/signs

19. Connor RF. Iron deficiency anaemia. Best Practice. London: BMJ Publishing Group Ltd; 2011.

20. Devalia V, Hamilton MS, Molloy AM et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. London: British Journal of Haematology 2014, 166: 496-513.

21. National Institute for Health and Care Excellence (NICE). Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Clinical guideline 184. London: NICE; 2014.

22. Royal College of Surgeons (RCS). Commissioning guide: Rectal bleeding. London: RCS; 2013.

23. World Health Organization (WHO). Guideline: Daily iron supplementation in adult women and adolescent girls. Geneva, Switzerland: WHO; 2016.

24. Chi AC, Neville BW, Krayer JW et al. Oral manifestations of systemic disease. Am Fam Physician 2010; 82: 1381-8.

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25. Tully AS, Trayes KP, Studdiford JS. Evaluation of nail abnormalities. Am Fam Physician 2012;85: 779-87.

26. Lichtin AE. MSD Manual Consumer Version. Overview of iron deficiency anaemia [Internet]. Kenilworth, NJ:MSD Manuals; [accessed 22 September 2016]. http://www.msdmanuals.com/home/blood-disorders/anemia/iron-deficiency-anemia.

27. Hill QA, Stamps R, Massey E, et al. Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia. London: British Society for Haematology; 2016.

28. National Institute of Health and Clinical Excellence (NICE) Clinical Knowledge Summaries. Anaemia - iron deficiency.

Newcastle upon Tyne: CKS; 2013.

29. Liu K, Kaffes AJ. Iron deficiency anaemia: a review of diagnosis, investigation, and management. Eur J Gastroenterol Hepatol 2012; 24: 109-16.

30. National Institute for Health and Care Excellence (NICE). Colorectal cancer: the diagnosis and management of colorectal cancer. Clinical guideline 31 (updated 2014). London: NICE; 2011.

31. Chakravorty S, Williams TN. Sickle cell disease: a neglected chronic disease of increasing global health importance. Arch Dis Child. 2015;100:48-53

32. Naik RP, Haywood C. Sickle cell trait diagnosis: clinical and social implications. Hematology Am Soc Hematol Educ

Program. 2015; 1:160-167

33. Killick SB, Bown N, Cavenagh J et al. British committee for Standards in Haematology guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 2016; 172: 187-207.

34. DeZern AE, Guinan EC. Aplastic anemia in adolescents and young adults. Acta Haematol. 2014; 132:331-339

35. Killick SB, Carter C, Culligan D et al.Guidelines for the diagnosis and management of adult myelodysplastic syndromes.

British Journal of Haematology. 2014; 164:503-525

36. Fenaux P, Haase D, Sanz GF et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 25:57-69

37. Giovanni M, Niscola P, Serrano KD et al. Anaemia of chronic disease. Best Practice. London: BMJ Publishing Group

Ltd; 2011

38. National Institute of Health and Clinical Excellence (NICE) Clinical Knowledge Summaries. Anaemia - vitamin B12 and folate deficiency. Newcastle upon Tyne: CKS; 2015.

39 Guidelines &protocols advisory committee. Cobalamin (vitamin B12) deficiency - investigation & management. Victoria,

BC: British Columbia Medical Services Commission; 2013.

40 Chavala SH Kosmorsky GS Lee MK. Optic neuropathy in vitamin B12 deficiency. European J Intern Med 2005; 16:447-8.

41 Lachner C Steinle NI Regenold WT. The neuropsychiatry of vitamin B12 deficiency in elderly patients. Journal

Neuropsychiatry Clin Neurosci 2012; 24: 5-15. 42 Badham J Zimmerman MB Kraemer K. The guidebook: nutritional anemia. Basel, Switzerland: Sight and Life Press;

2007.

43 Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem. 2000; 46:1277-83

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Guideline Development Group members

The following table lists members of the Guideline Development Group (GDG) nominated by their respective organisations and

the Clinical Governance Group. The GDG members have reviewed and provided feedback on the draft guideline relating to the

topic. Each member has completed a declaration of conflicts of interest, which has been reviewed and retained by the MOPH.

Guideline Development Group members

Name Title Organisation

Dr Reham Afifi Consultant Internal Medicine Al Ahli Hospital

Dr Majd Riadh Akbik Senior Specialist Family Medicine Primary Health Care Corp

Dr Ibrahim Ahmad A.H. Al Hijji Senior Consultant Haematologist,

Head of Clinical Haematology, NCCCR Hamad Medical Corporation

Dr Abdulhak A. Sadalla Alnuemi Consultant Internal Medicine Al Emadi Hospital

Dr Ahmad Al Sabbagh Senior Consultant Haematopathologist,

Director of the NCCCR laboratory Hamad Medical Corporation

Dr Ahmed M. Hussein Babiker Head of Registration Section & Clinical

Pharmacist

Dept of Pharmacy and Drug Control,

MOPH1

Dr Azza Abu Elrish Consultant Family Medicine Qatar Petroleum

Dr Ameena Ibrahim Fakhroo Consultant Family Medicine Primary Health Care Corp

Dr Abdul Hakeem Hamza Consultant Family Medicine Primary Health Care Corp

Dr Naseer Ahmad Masoodi Assistant Chair/Senior Consultant

Ambulatory General Internal Medicine Hamad Medical Corporation

Dr Tariq Sheikh Consultant Internal Medicine Al Ahli Hospital

Dr Ruba Taha Consultant Haematologist Hamad Medical Corporation

Responsibilities of healthcare professionals

This care map has been issued by the MOPH to define how care should be provided in Qatar. It is based upon a comprehensive

assessment of the evidence as well as its applicability to the national context of Qatar. Healthcare professionals are expected to

take this guidance into account when exercising their clinical judgement in the care of patients presenting to them.

The guidance does not override individual professional responsibility to take decisions which are appropriate to the

circumstances of the patient concerned. Such decisions should be made in consultation with the patient, their guardians, or

carers and should consider the individual risks and benefits of any intervention that is contemplated in the patient’s care.

1 Dr Ahmed Babiker attended the MOPH in his capacity as a Clinical Pharmacist and advisor on the availability of medications in Qatar.

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Acknowledgements

The following individuals are recognised for their contribution to the successful implementation of the National Guidelines

project.

Healthcare Quality Management and Patient Safety Department of the MOPH:

Ms Huda Amer Al-Katheeri, Acting Director & Project Executive.

Dr Alanoud Saleh Alfehaidi, Guideline & Standardisation Specialist.

Dr Ilham Omer Siddig, Guideline & Standardisation Specialist.

Ms Maricel Balagtas Garcia, Guideline Standardisation Coordinator.

Dr Rasmeh Ali Salameh Al Huneiti, Research Training & Education Specialist.

Mr Mohammad Jaran, Risk Management Coordinator.

Hearst Health International:

Dr Mehmood Syed, Middle East Clinical Director & Project Clinical Lead.

Mr Michael Redmond, Clinical Programmes Manager.

Ms Deepti Mehta, Editorial and Research Manager.

Ms Rebecca Cox, Editorial and Research Team Leader.

Ms Shuchita Deo, Lead Editorial Assistant.

Ms Siobhan Miller, Editorial Assistant.

Ms Fatima Rahman, Editorial Assistant.

Ms Tahmida Zaman, Editorial Assistant.

Ms Emma Ramstead, Information Specialist.

Dr Amy Glossop, Clinical Editor.

Dr Zara Quail, Clinical Editor.

Dr Sabine Fonderson, Clinical Editor.