Anaemia
Nov 2010
Overview
Iron deficiency anaemiaMacrocytic anaemiaHaemolytic anaemia
Recognition and management of bleeding disorders
Case history (1)
45yr old female3 month history of fatigue and shortness of breath on exertionO/E pallor ++FBC – Hb 6.2g/dl
Case history (1)
What further results are important in the full blood count?What further details are important in the clinical history and examination?What further investigations should be carried out?How should the patient be managed?
Full Blood Count
Hb 6.2 g/dl (12-16)WCC 7.0 x 109/l (4-11)Platelets 300 x 109/l (140-440)MCV 60fl (76-96)MCH 24 pg (27-32)
WCC differential –NBlood Film
Some causes of microcytic anaemia…..
AcquiredIron deficiencyAnaemia of chronic diseaseMyelodysplastic syndromesLead poisoning
More causes of microcytic anaemia…..
InheritedThalassaemiaSickle cell trait
What further details are important in the clinical history?
Dietary intake of ironSymptoms of malabsorption / weight lossOvert GI blood lossMenorrhagiaPregnancyOral iron therapyBleeding history/ family history of bleeding disorder
Iron Requirements
Males 0.5-1mg per dayMenstruating females 1-2mg per dayPregnant females 1.5-2.5mg per dayChildren 1mg per day
An adequate diet contains 15mg of iron, 10% of which is absorbed.
Dietary iron
Red meat , liver, beansAbsorbed in the duodenum and jejunumAbsorption enhanced by ascorbic acid, citrus fruitsAbsorption reduced by phytates, alkalis, tea, tetracyclines
Causes of iron deficiency anaemia
Inadequate intake
Failure of absorption
Increased blood loss
Increased requirements
Dietary ironIron supplementsGastrointestinal symptomsHx of Coeliac diseaseOvert blood loss from bowel or change of bowel habitMenorrhagiaPregnancy
Common causes of gastrointestinal bleeding
Oesophagus
Stomach
Small bowel
Hiatus herniaVaricesGastritis Ulcer CarcinomaUlcerMeckels diverticulumCarcinoma
Common causes of gastrointestinal bleeding
Colon
Rectum
Ulcerative colitisCarcinoma Diverticulitis
HaemorrhoidsUlcerationCarcinoma
Iron loss in pregnancy
Obligatory iron loss 150-200 mgFetal iron 200-370 mgIron in placenta and cord 30-170 mgIron in blood lost at delivery 90-310 mg
Total iron loss 470-1050mg
What further investigations should be carried out?
Serum ferritin +/- serum ironB12 / folateFaecal Occult Blood+/- Coeliac screen+/- Gastroscopy and/or colonoscopy+/- Gynaecology referral
Causes of raised ferritin levels
Acute inflammationAcute liver diseaseLymphomasSolid tumoursHaemochromatosis
How should the patient be managed?
Treat the underlying causeOral iron supplements
correct anaemiareplenish iron stores
IV ironmalabsorptionintolerance
Is there a role for blood transfusion?
Failure to respond to oral iron
Is the diagnosis correct?Is the patient taking the iron?Is there evidence of malabsorption?Is there evidence of persistent blood loss?
Case (2)
45yr old female3 month history of fatigue and palpitationsO/E pallor ++FBC – Hb 5.3 g/dl
Case 2
What further results are important in the full blood count?What further details are important in the clinical history and examination?What further investigations should be carried out?How should the patient be managed?
Full Blood Count
Hb 6.2 g/dl (12-16)WCC 7.0 x 109/l (4-11)Platelets 120 x 109/l (140-440)MCV 120fl (76-96)MCH 28pg (27-32)
WCC differential –NBlood Film
Some causes of macrocytosis…...
Megaloblastic anaemiaVitamin B12 deficiencyFolate deficiencyMyelodysplasia
More causes of macrocytosis….
Liver diseaseAlcohol excessHypothyroidismCytotoxic drugs
What further details are important in the clinical history?
DietSymptoms of malabsorption / weight lossFamily history of anaemia or autoimmune disordersThyroid diseaseAlcohol intake
What further investigations should be performed?
Blood filmB12, Folate, FerritinLiver function testsThyroid function tests
Coeliac screenIntrinsic factor and parietal cell antibodies?Bone marrow – only if above normal
Vitamin B12
Sources – liver meat fish and dairy productsDaily intake 3-30 microgramAdult daily requirement 1-2 microgramBody stores 3-5 mg in the liver (2-4 yr supply)Important for pyrimidine synthesis in the production of DNA
Vitamin B12 absorption
B12 attaches to intrinsic factor (IF) in the stomachIF – a glycoprotein secreted by the parietal cellsB12/IF passes to the terminal ileum where absorption takes place
Causes of B12 deficiency
Strict vegetarianismMalabsorption
Pernicious anaemiaGastrectomyCoeliac diseaseDisease involving the terminal ileum
ResectionCrohn’s disease
Pernicious anaemia
Autoimmune diseaseGastric atrophyAnti parietal cell antibodies 90%Anti intrinsic factor antibodies 70%
Often associated with other autoimmune disorders
B12 deficiency – clinical features
Related to anaemiaNeurological
Peripheral neuropathyLoss of vibration and position senseDemyelination of the cordIrreversible
Management
Lifelong replacement with B12 usually requiredIM Hydroxocobalamin 1000 microgram every 3 months
Folate
Dietary sources- eggs, green vegetables, liver, nutsAbsorbed in the jejumunDaily intake 600-700microgramDaily requirement 100 microgramStored in the liver (4-6 months supply)Important in DNA synthesis
Causes of folate deficiency
Dietary – infancy and old ageMalabsorption – coeliac diseaseIncreased utilisation – pregancy, lactation, haemolytic anaemiaAntifolate drugs – methotrexate, anticonvulsants
Management of folate deficiency
Treat underlying causeCorrect folate levels : oral folic acid 5-15mg dailyProphylactic folate to at risk groups eg pregnancy, congenital haemolytic anaemias
Haemolytic Anaemias
Haemolytic anaemia
Normal red cell life span 100-120 days
A haemolytic anaemia occurs if that life span is shortened
CongenitalAcquired
Mrs C
31 year old femaleHistory of recent “viral illness”C/O increasing tirednessNoticed to look jaundiced by her family
Mrs C
What laboratory investigations should be carried out?
How should the patient be managed?
Mrs C –laboratory results
FBC – Hb 7.7 g/dl Blood film – polychromasiaRaised reticulocyte countRaised bilirubinRaised lactate dehydrogenase (LDH)
Haemolytic Anaemia
How would you investigate the patient?
What are the causes of acquired haemolytic anaemia?
Idiopathic Secondary
A u to im m u ne A llo im m u ne D rug ind uced
Im m une N on Im m une
Acquired Haem olytic anaem ia
Autoimmune haemolytic anaemia
Warm AntibodyIdiopathicSecondary
CLLConnective tissue disordersLymphomasDrugs eg Methyldopa
Cold AntibodyIdiopathicSecondary
MycoplasmaInfectious mononucleosisLymphoma
Alloimmune Haemolytic Anaemia
Haemolytic transfusion reactions eg ABO mismatch
Haemolytic disease of the newborn eg Rhesus incompatibility
Non immune haemolytic anaemia
Red cell fragmentation
Infections
Chemical/ Physical
DIC, Cardiac valvesHUS, TTPMarch haemoglobinuria
Malaria, Clostridium
Drugs, chemicalsVenomsBurns
Clinical features of haemolytic anaemias
Symptoms related to anaemiaJaundiceIncreased incidence of pigmented gallstonesSplenomegalyLeg ulcers- sickle cell, hereditary spherocytosis
Warm autoimmune haemolytic anaemia
Antibody usually IgG – maximum activity @370
Any age, either sexSplenomegaly commonBlood film – microspherocytes, polychromasiaDirect Coombs test (DCT) positive
Warm autoimmune haemolytic anaemia
ManagementTreat the underlying causeCorticosteroidsSplenectomy Other immunosuppressants eg azathioprine, cyclosporinBlood transfusion – if life threatening
Cold autoimmune haemolytic anaemia
Antibody usually IgM – maximum activity @40
Raynauds PhenomenonPositive DCT – complementCold agglutinins – agglutination on blood film
Cold autoimmune haemolytic anaemia
ManagementTreat the underlying causeKeep the patient warmConsider immunosuppression
Haemolytic anaemia and infections
Direct damage to cells eg malariaToxin production eg clostridiumOxidant stress in G6PD deficiencyDIC eg meningococcusAutoantibody formation eg infectious mononucleosis
Inherited haemolytic anaemias
Red cell membrane defects
Disorders of red cell metabolism
Abnormal haemoglobins
Peter M
10 yr oldLife long history of recurrent anaemia and jaundiceFather gives similar history and required cholecystectomy when he was 20yr
Peter M – Laboratory investigations
Hb 9.2g/dlBlood film – microspherocytes, polychromasiaElevated bilirubinDCT negativeOsmotic fragility testing- increased haemolysisHereditary Spherocytosis
Hereditary Spherocytosis
Autosomal dominantVariable severityDefect in a red cell membrane proteinCells destroyed prematurely in the spleenSplenomegaly is common
Hereditary Spherocytosis
Splenectomy for severe casesIncreases the red cell survivalDefer until >6yrs
Folic acid
Abnormalities of Red Cell Metabolism
Glucose-6-phosphate dehydrogenase deficiencyPyruvate Kinase deficiency
Inherited haemolytic Inherited haemolytic anaemiasanaemias
Red cell membrane defects
Disorders of red cell metabolism
Abnormal haemoglobins
Abnormal Haemoglobins
Disorders of globin chain synthesis – the thalassaemias
Structural defects of haemoglobin eg sickle cell disease
Sickle cell disease - Pathogenesis
Chronic haemolytic anaemia caused by a point mutation in the globin gene Causes insolubility of Hb in the deoxygenated stateInsoluble chains crystallise in the red cells causing sicklingVascular occlusion
Sickle cell disease – clinical features
Vaso-occlusive crisesCommon precipitants are infection, dehydrationBone pain StrokeVisceral infarction – spleen, kidneysDactilytis - children
Sickle cell disease – clinical features
Sequestration crisesSickling with pooling of red cells in liver or spleen – severe anaemia, rapid enlarging liver or spleenAcute chest syndrome – chest pain, hypoxia, diffuse shadowing on CXR
Sickle cell disease – laboratory features
Hb 7-9 g/dlSickle cells on blood filmAbnormal haemoglobin electrophoresis
Sickle cell disease – management
GeneralAvoid known precipitantsFolic acidVaccinate, prophylactic penicillin (reduced splenic function)
Sickle cell disease – management
Vaso-occlusive crisesHydrationAnalgesia – opioidsAntibiotics if infection
Sickle cell disease – management
TransfusionFor severe anaemiaRed cell exchange
Severe crisesLung sequestrationStokeHepatic sequestration
Other sickling disorders
Sickle cell traitBenign conditionUsually asymptomaticAdvice re carrier state
The Thalassaemias
2 globin genes4 globin genes
Autosomal recessive disordersCharacterised by ineffective haemopoiesis
The Thalassaemias
ThalassaemiaSeverity depends on the number of genes deletedTrait – 1 or 2genes deleted, mild anaemia, hypochromic microcytic filmHb H disease – 3 genes deleted , splenomegaly, Hb 6-10g/dl, hypochromic microcyticHyrdrops fetalis – 4 gene deletion, death in utero
The Thalassaemias
ThalassaemiaTrait – mild hypochromic microcytic anaemia, advice re carrier state thal major
Severe anaemia @ 3-6 months whem switch is made from fetal HbHepatosplenomegalyExpansion of bones
The Thalassaemias
Laboratory featuresSevere anaemiaHypochrominc microcytic cells, target cellsBM erythroid hyperplasiaDNA analysis
The Thalassaemias
ManagementRegular transfusionIron chelationBone marrow transplantation
Reduced life expectancy
BLEEDING DISORDERSRecognition and continuing
care
TISSUE FACTOR
+TFVIITISSUE FACTOR
COMPLEXXI
IXX
VIII
V
PROTHROMBINTHROMBIN
VII VIIa
FIBRINOGEN
Va
VIIIa
XIa
IXaXa
TRIGGER
FIBRIN
Vesselinjury
PlateletRelease rxn
PlateletAggregation
Vasoconstriction CoagulationCascade
StableHaemostatic Plug
Recognition of Bleeding Disorders
The Bleeding History
Personal historyEpistaxisBleeding post surgeryBleeding post dental extractionMenorrhagiaHistory of anaemiaEasy bruising
Family history NB
The Bleeding history
Coag. DeficienciesProlonged bleeding after trauma and surgery (>24 hrs).Haemarthroses Muscle bleeding.
Platelet defects and VWD:Bruising.Petechiae or purpura.Epistaxis.Menorrhagia Prolonged post-trauma bleeding
Investigations
Investigation of bleeding disorders
FBC - platelet countProthrombin time (PT) - factors V, VII, XActivated partial thromboplastin time (APTT)- factors VIII, IX, XI, XIIFibrinogen
Investigation of bleeding disorders
Von Willebrand FactorSpecific clotting factor assaysPlatelet function testing
Treatment of bleeding disorders- general principles
Avoid IM injections and NSAIDsAvoid delay in treating the patient. Treat on suspicion of a bleedListen to the patient - he/she has lifelong experienceRecord any treatment given including batch numbers to ensure full traceability of factor concentratesSeek help early
Treatment of bleeding disorders- general principles
VaccinationAgainst Hepatitis A and BGive by SC routeChidhood vaccinationsCheck antibody levels annually
Haemophilia
Haemophilia A VIII deficiency sex-linked, 1/3rd carriers <50% VIIIC.1:20,000 births
Haemophilia B IX deficiencysex-linked, 1/3rd carriers <50% IX.1:100,000
These are clinically indistinguishable
Haemophilia
Mild haemophilia ( 5 - 20 %): – bleed only with trauma and surgery.
Severe haemophilia( < 1%) : – Haemarthroses 2-8 times/month.– Muscle bleeds.– Intracerebral bleeding– Prolonged bleeding with trauma and
surgery.
HAEMOPHILIA - HAEMARTHROSIS
Haemophilia Care
Treatment of acute bleedsManagement of HIV and Hep C infectionManagement of arthropathyDental review / dental hygieneAnnual clinic reviewVaccination
Haemophilia treatment
A bleed or potential bleed requires immediate treatmentIf in doubt manage as a bleed Identify site of suspected bleed and assess for compression of vital structuresAvoid unnecessary investigations - eg Xrays, coagulation profiles – unless clinically indicated
Haemophilia treatment
FACTOR VIII and IX
Previously plasma derived
Now all recombinant in Ireland
Delivered directly to patients homes
Haemophilia - treatment
Moderate and severe bleeds need admission
Daily factor concentrateImmobilisationAnalgesiaPhysiotherapy
Von Willebrand Disease
19265yr old girl – died at 13yr during 4th menstrual period4 siblings died from gastrointestinal haemorrhageBoth parents had significant bleeding historyVWF – identified 1950s, purified 1972, sequenced 1985
Von Willebrand Disease
Up to 1% of the population125 / million have a clinically significant bleeding disorderAutosomal inheritance
Von Willebrand factor
Large glycoprotein produced by endothelial cells and megakaryocytes Mediates platelet to endothelial adhesion Mediates platelet to platelet interactionCarrier protein for Factor VIII
Von Willebrand Disease
MILD/MODERATE BLEEDING TENDANCY
mucocutaneous bleedingeasy bruisingepistaxismenorrhagiarecurrent iron deficiencyfamily history
VWD diagnosis
Coag screen often normal
VWF - quantiative assays
VWF Ricof - functional assay
VWD - diagnosis
Levels increased by menstrual cycle, OCP, pregnancy, smoking, stress, inflammatory disorders
Repeat sampling recommendedequivocal resultsminor abnormalitiesstrong personal or family history
VWD Treatment
Avoid NSAIDsAvoid IM injectionsVaccinate against Hepatitis A and BTreat anaemiaDental hygiene
Very few patients require treatment with clotting factor concentrate
VWD TREATMENT -Specific measures
Clotting factor concentrates
DDAVP
Cyclokapron
DDAVP
Promotes release of VWF and factor VIII from endothelial cells0.3ug/kg in 100mls N/Saline over 30 minsAverage response is a threefold rise in VWF and FVIIITreatment of choice in responsive patients for spontaneous bleeding , trauma or minor surgeryIntra nasal DDAVP
VWD TREATMENT -Specific measures
Cyclokapron Antifibrinolytic agentStabilises clotGiven orallyProvides adequate cover for minor procedures or dental work
Top Related