anaemia

1. ANAEMIA
Appleh Sedem
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2. OUTLINE
– INTRODUCTION
– EPIDEMIOLOGY
– AETIOLOGY
– PATHOPHYSIOOGY
– CLINICAL PRESENTATION
– INVESTIGATION
– TREATMENT
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3. INTRODUCTION
– Anemia is a decrease in either Haemoglobin or circulating red
blood cells (RBCs), resulting in reduced oxygen-carrying capacity
of the blood.
– Anemia is defined by the WHO as hemoglobin (Hb) less than 13
g/dL (130 g/L; 8.07 mmol/L) in men or less than 12 g/dL (120 g/L;
7.45 mmol/L) in women.
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4. EPIDEMIOLOGY
– According to the World Health Organization (WHO), almost 1.6
billion people (25% of the world’s population) are anemic.
– Iron deficiency is the leading cause of anemia worldwide,
accounting for as many as 50% of cases.
– Anaemia is twice as prevalent in females as in males.
– Anaemia of chronic disorders is commonplace in populations with
a high incidence of chronic infectious disease and this is in part is
worsened by the socioeconomic status.
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5. AETIOLOGY
– Inadequate/decreased RBC production
– Increased RBC destruction
– Red blood cell loss; acute or chronic
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6. CLASSIFICATION
– Microcytic , Macrocytic, Normocytic anaemia
– Anaemia of Inflammation
– Haemolytic anaemias
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7. ERYTHROPOIESIS
• RBC mass is maintained by feedback mechanisms that regulate levels of
erythropoietin(EPO).
• Reduced oxygen-carrying capacity is sensed by renal peritubular cells.
• RBCs are destroyed by the cells of the reticuloendothelial system found in the spleen
and bone marrow.
• Iron is removed from the haem component of haemoglobin, transported back to the
bone marrow for reuse.
• The pyrole ring from globin is excreted as conjugated bilirubin by the liver, and the
polypeptide portion enters the body's protein pool.
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9. DIAGNOSIS
– History
• Acute, Chronic
• Coexisting conditions : cardiovascular, renal disease., menstrual
history, alcohol consumption, diet
– Physical examination: pallor , tachycardia, hypotension, dizziness,
High-output heart failure and hypovolemic shock
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10. DIAGNOSIS
– Diagnostic testing:
Complete blood count (CBC), reticulocyte count ,peripheral smear
• Hb: normal range: Male, 13.5-17.5 g/dl.Female, 12-16g/dl
• Hct : Male, 41-53% . Female: 36-46%
• Mean cellular volume (MCV): Measures the mean volume of the RBCs.
Reference range: 80–96 fL.
Microcytic: MCV <80 fL , Normocytic: MCV 80–96 fL, Macrocytic: MCV >96 fL
• Red cell distribution width (RDW) : variability in RBC size, important finding
in anemic patients.
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11. DIAGNOSIS
• Mean cell haemoglobin (MCH): concentration of Hgb in each cell, and an elevated
level is often indicative of a hemoglobinopathy.
• Mean cell haemoglobin concentration (MCHC): < 30% indicates hypochromia
• The relative reticulocyte count: measures the percentage of immature red cells in
the blood and reflects production of RBCs in the bone marrow .
Normal range:0.4%–2.9%.
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12. DIAGNOSIS
• The reticulocyte index (RI) is a determination of the BM’s ability to respond to
anemia and is (normally 0.5-2.5 %).
RI <2 :indicates decreased production of RBCs (hypoproliferative anemia).
RI >2 with anemia may indicate a compensatory increase in RBC production
caused by hemolysis or bleeding (hyperproliferative anemia)
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14. IRON DEFICIENCY ANAEMIA
– Daily iron intake and stores are unable to meet the RBC and other body tissue
needs.
– A diet deficient in iron, parasitic infestations, increased physiological demand,
blood loss, decreased absorption (antacids, tetracyclines, PPI)
– The body contains approximately 3.5g of iron, of which 2.5g are found in Hgb.
– Iron is stored as ferritin
– Iron is transported around the body bound to a serum protein called
transferrin.
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15. IRON DEFICIENCY ANAEMIA
– Iron is best absorbed in its ferrous (Fe2+) form.
– Animal sources of iron, heme iron, are better absorbed than plant sources,
nonheme iron.
– The daily recommended dietary allowance for iron is 8 mg in adult males and
postmenopausal females and 18 mg in menstruating females
– Manifestations of IDA : Weakness, dizziness, increased heart rate, decreased
exercise tolerance , pica (compulsive eating of nonfood items), and
pagophagia (compulsive eating of ice), Koilonychia(spoon shaped nails)
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17. DIAGNOSIS OF ANEMIA
LABORATORY FINDINGS
CBC, Peripheral smear, Serum iron, TIBC
• low serum iron
• low ferritin levels: Male: 15-200ng/l, Females: 12-150ng/l
• high TIBC
• Low Hb and Hct (microcytic hypochromic)
• Low MCV
• Low reticulocyte count
Peripheral blood smear: microcytic and hypochromic with poikilocytes
(often pencil shaped) .
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18. GOALS OF TREATMENT
– normalize the Hgb and Hct concentrations.
– replenish iron stores
– Prevent complications
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19. NON PHARMACOLOGICAL TREATMENT
– Food high in iron: animal liver, fortified cereals/oatmeal, beef, eggs, spinach,
lentils, beans.
– Orange juice and other ascorbic acid–rich foods can be includedwith meals
to potentially increase absorption.
– Milk and tea reduce absorption and should be consumed in moderation.
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20. TREATMENT
– ORAL IRON THERAPY
• ferrous sulphate 20% of elemental iron
• Ferrous gluconate 33% elemental iron
• Ferrous fumarate 11% elemental iron
S/E: dark discoloration of feces, constipation or diarrhea, nausea,
vomiting.
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21. TREATMENT
– PARENTERAL IRON THERAPY
Dose of iron(mg)=whole blood haemoglobin deficit(g/L) x body weight(kg) x 0.22
• Iron dextran, IM,IV
– The test dose for adults is 25 mg of iron dextran
– A dose of 1000mg over 1 hour
• Iron sucrose IV
• Sodium ferric gluconate IV
• Ferumoxytol IV
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22. TREATMENT
– S/E: staining of the skin, pain at the injection site, anaphylaxis
nausea, vomiting, hypotension, Increased risk of infections
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23. MACROCYTIC
ANAEMIAS
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24. MACROCYTIC ANAEMIAS
– Macrocytic anemias : Megaloblastic & non-megaloblastic anaemia
– Non megaoblastic anaemias : liver disease, hypothyroidism, alcoholism
– The common biochemical defect in all megaloblastic anaemias is the
inhibition of DNA synthesis in maturing cells.
• The rate of RNA and cytoplasm production > the rate of DNA production.
• Impaired maturation process resulting in immature large RBCs
(macrocytosis).
• RNA and DNA synthesis depend on a series of reactions catalyzed by
vitamin B12and folate
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25. Vitamin B12 deficiency
– Major causes: inadequate intake, malabsorption syndromes, and inadequate utilization.
– Common in strict vegans and their breast fed infants
– Risk factors: age, gastric acid–suppressing agents, metformin
• Vitamin B12 is released from protein complexes and bound to intrinsic factor.
• Intrinsic factor is essential for the absorption of vitamin B12.
• Transcobalamin III is responsible for transporting vitamin B12 through cell membranes and
delivering it to the liver and other organs.
• Symptoms develop slowly: weakness, sore tongue, symmetric numbness or tingling in the
extremities, vision problems, ataxia
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26. FOLIC ACID DEFICIENCY
– Inadequate intake, decreased absorption, and increased folate
requirements, alcoholism, increase in the rate of cellular division
– Drugs : azathioprine, 6-mercaptopurine, 5 fluorouracil, hydroxyurea,
zidovudine
– Folate antagonists; is methotrexate, trimethoprim
– generally 3 mcg/kg/day, daily intake of 200 mcg is recommended.
– Dietary folic acid is in the polyglutamate form and must be enzymatically
deconjugated in the GI tract to the monoglutamate form.
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27. NON PHARMACOLOGICAL
MANAGEMENT
– Intake of foods containing Vit B12 ; fortified cereals, fish, animal liver,
milk, clams, yogurt.
– dietary sources of folate include fresh, green leafy vegetables, citrus
fruits, yeast, mushrooms, dairy products, and animal organs such as
liver and kidney.
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28. LABORATORY FINDINGS
In macrocytic anemias,
• MCV is elevated greater than 100fL,
• Low reticulocyte count
• low serum vitamin B12 level < 200 pg/mL [148 pmol/L])
• Low Hct.
• Serum folate levels < 2.7 ng/mL (7 nmol/L) within
• The RBC folate level < 150 ng/mL [ 340 nmol/L])
• High homocysteine
* Schilling’s test
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29. TREATMENT
– Vitamin B12 deficiency
• hydroxocobalamin 1 mg IM
• oral cyanocobalamin(1,000-
2,000mcg) in Pernicious anemia
S/E: hyperuricemia, hypokalemia
– Folic acid,
1 - 5 mg daily, 4 months
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30. ANAEMIA OF
INFLAMMATION
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31. ANAEMIA OF INFLAMMATION
– Anaemia of critical illness, Anemia of chronic disease
– (HIV), autoimmune conditions, cancer, heart failure
– Decreased production of endogenous EPO, reduced RBC life span, and
active bleeding.
– Additional comorbid factors include nutritional deficits such as poor
oral intake and altered absorption of vitamins and minerals
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32. PATHOPHYSIOLOGY
• During infections, inflammation and cancer, the inflammatory cytokines, in
particular interleukin-6 released from macrophages
• Inhibit the production of EPO or decrease RBC production
• lead to an increased production of hepcidin.
• Hepcidin, a peptide produced by hepatocytes, plays a key role in iron availability.
– Increased uptake of iron by hepatocytes;
– Reduced iron absorption;
– Reduced release of iron from macrophages
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33. LABORATORY FINDINGS
– Mild to moderate anaemia, Hb 7.0-9,9 g/dl
– May coexist with IDA and Folate deficiency
– Decreased serum iron level
– Decreased TIBC
– Ferritin is normal or increased ( usually increased in inflammation)
– Low HCT
– Low reticulocyte count
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34. AI IDA
Iron L L
Transferrin L or NL H
Transferrin saturation L L
Ferritin H or NL L
Soluble transferrin receptor NL H
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35. TREATMENT
– Erythropoiesis-stimulating agents
– Recombinant epoetin alfa
• 50 to 100 units per kilogram
three times per week
– Recombinant darbepoetin alfa.
• 0.45 mcg per kilogram once weekly,
– S/E increases in blood pressure,
• nausea, headache,
• fever, bone pain, fatigue.
• seizures, thrombotic events,
allergic reactions
– Transfusion of packed red blood
cells <7-8 g/dL
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36. HAEMOLYTIC
ANAEMIAS
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37. HAEMOLYTIC ANAEMIAS
– Haemolytic anaemias account for approximately 5% of all anaemias.
– Genetic disorders: Sickle cell anemia, Thallasemia, G6PD deficiency
– Acquired disorders: Autoimmune infections
– reduced life span of the erythrocytes.
– Anaemia is usually normochromic and normocytic.
– Clinical manifestations: malaise, fever, abdominal pain, dark urine and jaundice.
– haemoglobulinaemia, hyperbilirubinaemia, reticulocytosis and increased
urobilinogen levels in the urine.
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38. AUTOIMMUNE HAEMOLYTIC ANAEMIA
– consists of warm autoimmune haemolytic anaemia (WAIHA) and cold
autoimmune haemolytic anaemia also known as cold agglutinin disease
(CAD).
– idiopathic and acquired forms, and the condition is found in all races.
– The most common form being idiopathic WAIHA
– Idiopathic CAD tends to present in middle age.
– WAIHA is frequently associated with other diseases with an immunological
component; chronic lymphocytic leukaemia, systemic lupus erythematosus
and hepatitis B.
– Acquired CAD ; viral or bacterial infections
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39. PATHOPHYSIOLOGY
– Drugs : Cephalosporins, Dapsone, Levofloxacin, Methyldopa, Pencillins
– autoantibodies agglutinate or lyse the patient's own erythrocytes.
– In WAIHA, the haemolysis is usually extravascular and mediated by IgG.
These antibodies react best at body temperature.
– CAD is usually mediated by IgM and is capable of fixing complement.
– The IgM antibody attaches to the erythrocytes and causes them to
agglutinate at temperatures below 37 °C
– resulting in impaired blood flow to fingers, toes, nose and ears
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40. – painful fingers and toes with purplish discolouration associated with
cold exposure.
– A positive direct Coomb's test indicates the presence of antibodies to
red blood cells.
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41. TREATMENT
– WAIHA
• high-dose corticosteroids.
• azathioprine or cyclophosphamide.
• Blood transfusions
– CAD
• Avoidance of cold exposure can minimize exacerbations.
• RBC transfusions at 37°C
• Rituximab
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42. THALASSEMIA
– Thalassemia syndromes are inherited disorders characterized by reduced
Hgb synthesis associated with mutations in either the α- or β-gene of the
molecule .
– More than 100 β thalassaemia mutations have been identified, and they
tend to produce severe anaemia.
– Abnormal form or inadequate amount of haemoglobin
– The α thalassaemias are more common, whilst the severe forms lead to
death in utero or infancy.
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43. PATHOPHYSIOLOGY
– Alpha thalassemia : no α chain production (α0 thalassaemia) or reduced
production of a chain (α+ thalassaemia).
• Excess of beta, gamma chains
• Hb is unstable, forms insoluble precipitates that damage red cell membrane
• Damage to erythrocyte precursors
–
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44. PATHOPHYSIOLOGY
– Beta thalassemia: reduced or absent production of the globin β
chain.
• Relative excess of α chain which when unpaired become unstable
and precipitates in the red cell precursors.
• There is ineffective erythropoiesis and those mature cells that reach
the circulation have a shortened life span.
– Bone deformity and growth retardation
– splenomegaly
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45. INVESTIGATIONS
– Peripheral smear: microcytic hypochromic RBCs, along with
poikilocytosis and nucleated RBCs.
– Hgb electrophoresis : β-thalassemia showing an increased
percentage of Hgb A2 and Hgb F.
– The diagnosis of α-thalassemia is confirmed by α-globin gene
analysis.
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46. TREATMENT
– RBC transfusions to maintain an Hgb level of 9–10 g/dL .
– Chelation therapy : transfusion-associated iron overload. Ferritin >1000
ng/mL.
• Deferoxamine, 40 mg/kg SC or IV over 8–12 hours of continuous infusion.
– Hydroxyurea (15–35 mg/kg/d) to increase Hgb F
– Stem cell transplantation (SCT)
*Prevention is actively explored with genetic counselling programmes
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47. G6PD DEFIECIENCY
– Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a recessive
hereditary disease and affects approximately 400 million people
worldwide.
– There are more than 300 different forms of G6PD deficiency, only
some of which cause anaemia.
– It causes anaemia when the individual is exposed to a trigger factor.
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48. PATHOPHYSIOLOGY
– G6PD is an erythrocyte enzyme that is indirectly involved in the production of
reduced glutathione.
– Glutathione is produced in response to, and protects red cells from, oxidising
agents.
– G6PD is essential for the production of (NADPH) in erythrocytes.
– If there is a deficiency in G6PD, this decreases the production of NADPH which is
needed to keep glutathione in a reduced form.
– In G6PD deficiency, if the erythrocytes are exposed to an oxidising agent, the cell
membrane becomes damaged
– haemoglobin becomes oxidised and forms what are known as Heinz bodies.
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49. – Drugs to be avoided : Ciprofloxacin, Dapsone , Methylene blue, Primaquine ,
Nalidixic acid , Sulphonamides(including co-trimoxazole)
– Diagnosis: History and clinical findings, G6PD activity
– Treatment:
• Hydration
• Bood transfusions
• Vitamin E
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50. STG, 2017
– IRON DEFICIENCY ANEMIA
1st Line treatment
• Ferrous sulphate (Dried or anhydrous),oral
200mg (65mg elemental iron) 8 hourly for 3-
6months
OR
• Ferrous fumarate, oral
200mg (65mg elemental iron) 8 hourly
Children:3-6mg elemental iron/kg for 3-6m
– 2nd line treatment
– Iron sucrose, IV 9slow bolus injection over 2-5
mins)
200mg every 3 days for 5 doses
Children:0.5mg/kg every 4 weeks for 12
weeks(max 100mg per dose)
– Iron dextran, IV (slow bolus or deep IM
injection)
25-100mg daily as needed
N.B Not recommended in children
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51. STG,2017
– Vitamin B12 deficiency
• Vitamin B12 (Hydroxycobalamin), IM
Img every other day for 6 doses
Then, I mg every 3 months for life
Children
Img stat
Then, Img every 3 moths for life
– Folate deficiency
• Folic acid, oral
5 mg daily
Children
2.5-5mg daily
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52. STG, 2017
– Severe symptomatic anemia
• Blood transfusion with packed cells
Then , treat for signs of cardiac failure if present
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53. REFERENCE
– Standard Treatment Guidelines (2017). Ministry of Health. Ghana
National Drugs Programme. 7th Edition. Pp 62-65
– Koda-kimble, Mary A. & Lloyd Y. (2012) Applied therapeutics: The
clinical use of drugs.10th Edition. Baltimore, Md: Lippincott
Williams & Wilkin. Pp232-250
– Walker R, Whittlesea C (2012). Clinical Pharmacy and Therapeutics.
Churchill Livingston, Elsevier (5thEdition) Walker pp 779, 783
– Porter R., Kaplan J.(2011).The merck manual of diagnosis and
Therapy. 19th Edition. Whitehouse station, NJ. Pp 1046-1070
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