ANAEMIA

1. ANAEMIA

2. The main function of the red blood cells is oxygen transport. Hence a functional definition of anaemia is 'a state in which the circulating red-cell mass is insufficient to meet the oxygen requirements of the tissues'. • However, many compensatory mechanisms can be brought into play to restore the oxygen supply to the vital centers and therefore in clinical practice this definition is of limited value. • For this reason anaemia is usually defined as 'a reduction of the haemoglobin concentration, red-cell count, or hematocrit to below normal levels'. • It has been extremely difficult to establish a normal range of haematological values, and hence the definition of anaemia usually involves the adoption of rather arbitrary criteria. For example, the World Health Organization recommends that anaemia should be considered to exist in adults whose haemoglobin levels are lower than 13 g/dl (males) or 12 g/dl (females).

3. DEFINITIONS IN HAEMATOLOGY Mean corpuscular Haematocrit volume (MCV) Red cells count Mean corpuscular Haemaglobin x 10 haemaglobin (MCH) Red cells count Mean corpuscular Haemaglobin x 10 haemaglobin Haematocrit concentration (MHCH) = N = 80 – 96 μ = N = 27 – 33 pg N = 32 – 35 g/dL =

4. Clinical features • Symptoms (all non - specific): • fatigue • headaches • faintness • breathlessness • angina of effort • intermitent claudication • palpitations

5. Signs: • Non / specific signs include: • pallor • tachycardia • a full pulse • systolic flow murmur • cardiac failure • ankle oedema • rarely papilloedema and retinal haemorrhage in an acute bleed • Specific signs: • koilonychia – spoon-shape nails seen in iron deficiency anaemia • jaundice – haemolytic anaemia • bone deformities – thalassemia major • leg ulcers – sickle cell disease

6. Classification: • Hypochromic microcytic with low mean corpuscular volume (MCV) • Normochromic normocytic with a normal MCV • Macrocytic with a high MCV • Special investigations: • bone marrow aspiration from the sternum or posterior illiac crest is performed to: • confirm a diagnostic made from peripheral blood count • determine the cellularity of the marrow • determine the type of erythropoiesis • determine the proportion of the various lines • see wether the marrow is unfiltrated • determine the size of the iron stores

7. MYCROCYTIC ANAEMIA • small cells (microcytes) • low MCV (< 80 μL) • ↓ iron content • ragged normoblasts • small cells (microcytes) • low MCV (< 80 μL) • normal iron content hyperplastic } Iron deficiency anaemia } Thalassaemia Sideroblastic anaemia

9. IRON DEFICIENCY • the commonest cause of mycrocitic anaemia • the average daily diet contains 15 – 20 mg of iron, but only 10% is absorbed • absorption: • duodenum and jejunum • ferrous iron is absorbed better than ferric • gastric acidity helps to keep iron in the ferrous state and soluble in the upper gut

10. transport in the blood: • transported in the plasma bound to transferin, beta globuline synthesized in the liver • iron stores – in the tissues as ferritin and haemosiderin (1000 – 1500 mg) • requirements: • each day 0.5 – 1 mg of iron are lost in the faeces, urine and sweat • menstruating women lose 0.7 mg iron / day of menstruation • pregnancy and groth ↑ iron demand

11. CAUSES OF IRON DEFICIENCY • Poor intake • Decreased absorption • Increased demands • Blood loss • The commonest cause of iron deficiency: • Blood lost from G.I. tract • Menstruation

12. The average American diet contains 10–15 mg of iron per day. About 10% of this amount is absorbed. Absorption occurs in the stomach, duodenum, and upper jejunum. • Dietary iron present as heme is efficiently absorbed (10–20%) but non heme iron less so (1–5%), largely because of interference by phosphates, tannins and other food constituents. • Small amounts of iron—approximately 1 mg/d—are normally lost through exfoliation of skin and mucosal cells. • There is no physiologic mechanism for increasing normal body iron losses.

14. Menstrual blood loss plays a major role in iron metabolism. The average monthly menstrual blood loss is approximately 50 mL or about 0.7 mg/d. However, menstrual blood loss may be five times the average. • To maintain adequate iron stores, women with heavy menstrual losses must absorb 3–4 mg of iron from the diet each day. • This strains the upper limit of what may reasonably be absorbed and women with menorrhagia of this degree will almost always become iron deficient without iron supplementation.

15. By far the most important cause of iron deficiency anemia is blood loss, especially gastrointestinal blood loss. • Prolonged aspirin use, or the use of other anti-inflammatory drugs, may cause it even without a documented structural lesion. • Iron deficiency demands a search for a source of gastrointestinal bleeding if other sites of blood loss (menorrhagia, other uterine bleeding and repeated blood donations) are excluded.

16. Chronic hemoglobinuria may lead to iron deficiency since iron is lost in the urine, but this is uncommon. • Traumatic hemolysis due to a prosthetic cardiac valve and other causes of intravascular hemolysis (eg, paroxysmal nocturnal hemoglobinuria) should also be considered. • Frequent blood donors may also be at risk for iron deficiency.

18. Symptoms and Signs • -anemia syndrome • s/s due to iron defficiecy • s/s due to disease which cause chronic blood lose • Severe deficiency causes skin and mucosal changes, including a smooth tongue, brittle nails, and cheilosis. • Dysphagia because of the formation of esophageal webs (Plummer–Vinson syndrome) also occurs.

19. Clinical features • In humans, unusual syndromes of food craving (pica) have been recorded and appear to respond to iron supplementation: this includes craving for soils and the ingestion of silica-rich earths as a cult practice in black populations of the Southern United States—geophagia. • Pagophagia (ice-craving) combined with the abnormal taste preferences of pregnancy may account for the bizarre food craving that constitutes part of the folklore of pregnancy. • Severe iron deficiency may occasionally be associated with splenomegaly and the signs of underlying disease include peripheral oedema (hypoalbuminaemia associated with massive hookworm infection) and oronasal telangiectasia associated with Osler–Rendu–Weber disease (hereditary haemorrhagic telangiectasia).

20. Clinical features: • brittle nails • spoon – shaped nails (koilonychia) • atrophy of the papillae of the tongue • angular stomatitis • brittle hair • dysphagia and glossitis (plummer – Vinson or Paterson Brown Kelly syndrome) • parotid gland enlargement, splenomegaly and failure to grow

24. Smooth, bald, burning tongue; Iron deficiency anemia

25. Cancer of uterus Gastric cancer/ colonic cancer PeptIc ulcer

26. investigations: • Ht, Hb, RBC low ; teiculocyte low • the red cells are microcytic (MCV < 80 fL) and hypochromic (MCH < 27 pg) • poikilocytosis (variation in shape) and anisocytosis (variation in size) • target cells • hypersegmentation of polymorphs • serum iron falls • iron blinding capacity ↑ • bone marrow – erythroid hyperplasia with ragged normoblasts • ring sideroblast other investigations: • the G.I. tract - endoscopy

28. Poikilocytosis is a term which indicates that red cells of abnormal shape are present on the blood film. Of itself it is fairly non-specific. Some particular types of poikilocyte are very informative, however.

29. Bone marrow in iron deficiency

31. Iron deficiency develops in stages • The first is depletion of iron stores. At this point, there is anemia and no change in red blood cell size. The serum ferritin will become abnormally low. A ferritin value less than 12 mcg/L is a highly reliable indicator of iron deficiency. Bone marrow biopsy for evaluation of iron stores is now rarely performed because of intraobserver variation in its interpretation. • After iron stores have been depleted, red blood cell formation will continue with deficient supplies of iron. Serum iron values decline to less than 30 mcg/dL and transferrin levels rise, leading to transferring saturation of less than 15%.

32. In the early stages, the MCV remains normal. Subsequently, the MCV falls and the blood smear shows hypochromic microcytic cells (see blood smear). • With further progression, anisocytosis (variations in red blood cell size) and poikilocytosis (variation in shape of red cells) develop. • Severe iron deficiency will produce a bizarre peripheral blood smear, with severely hypochromic cells, target cells, hypochromic pencil-shaped cells and occasionally small numbers of nucleated red blood cells. The platelet count is commonly increased.

34. Differential Diagnosis • Other causes of microcytic anemia include anemia of chronic disease, thalassemia and sideroblastic anemia. • Anemia of chronic disease is characterized by normal or increased iron stores in the bone marrow and a normal or elevated ferritin level; the serum iron is low, often drastically so, and the total iron-binding capacity (TIBC) is either normal or low. • Thalassemia produces a greater degree of microcytosis for any given level of anemia than does iron deficiency. Red blood cell morphology on the peripheral smear is abnormal earlier in the course of thalassemia.

35. Iron Deficiency AnemiaEssentials of Diagnosis • Serum ferritin < 12 mcg/L. • Caused by bleeding unless proved otherwise. • Responds to iron therapy.

36. sideroblastic anaemia • Classification: • Congenital: • “X” linked disease – transmitted by females • Acquired: • primary or idiopathic • secondary: • drugs • alcohol • lead • myeloproliferative disorders • leukaemias • secondary carcinoma • other systemic disorders (connective tissue disease)

37. The sideroblastic anemias are a heterogeneous group of disorders in which hemoglobin synthesis is reduced because of failure to incorporate heme into protoporphyrin to form hemoglobin. • Iron accumulates, particularly in the mitochondria. • A Prussian blue stain of the bone marrow will reveal ringed sideroblasts, cells with iron deposits encircling the red cell nucleus. • The disorder is usually acquired. Sometimes it represents a stage in evolution of a generalized bone marrow disorder (myelodysplasia) that may ultimately terminate in acute leukemia. • Other causes include chronic alcoholism and lead poisoning.

38. Patients have no specific clinical features other than those related to anemia. • The anemia is usually moderate, with hematocrits of 20–30%, but transfusions may occasionally be required. • Although the MCV is usually normal or slightly increased, it may occasionally be low, leading to confusion with iron deficiency. • The peripheral blood smear characteristically shows a dimorphic population of red blood cells, one normal and one hypochromic. • In cases of lead poisoning, coarse basophilic stippling of the red cells is seen.

39. The diagnosis is made by examination of the bone marrow. • Characteristically, there is marked erythroid hyperplasia, a sign of ineffective erythropoiesis (expansion of the erythroid compartment of the bone marrow that does not result in the production of reticulocytes in the peripheral blood). • The iron stain of the bone marrow shows a generalized increase in iron stores and the presence of ringed sideroblasts. • Other characteristic laboratory features include a high serum iron and a high transferrin saturation. • In lead poisoning, serum lead levels will be elevated.

40. thalassaemia • Deficiency in the synthesis of the globin chains of haemoglobin in addition, the accumulation of abnormal chains within the red cell leads to its early destruction. • The severity of the thalassaemia will depend on the amount of the haemoglobin A2 and F present. • Clinically β-thalassaemia can be divided into: • thalassaemia major, with severe anaemia • intermedia, with moderate anaemia rarely requiring transfusion • minor, the symptomless heterozygous carrier state

42. symptoms: • failure to thrive • intermittent infection • severe anaemia • extramedullary haemopoiesis → hepatosplenomegaly and bone expansion  thalassaemic facies

44. investigation: • blood count: • moderate to severe anaemia (↓MCV, MCH↓) • reticulocyte ↑ • white cells and platelets = N • blood film: • hypochromic and microcytic picture • Howell – Jolly bodies • high ferritin levels • haemoglobin electrophoresis (HbF ↑; HbA absent)

46. β-Thalassaemia trait (minor) • asymptomatic • no anaemia, red cells hypochromic and microcytic α-Thalassaemia • two main form: • deletion of only alpha chain gene • deletion of both alpha chain genes → no alpha chains are produced

47. Thalassemia major Thalassemia minor

48. Differential Diagnosis • Mild forms of thalassemia must be differentiated from iron deficiency. • Compared to iron deficiency anemia, patients with thalassemia have a lower MCV, a more normal red blood count and a more abnormal peripheral blood smear at modest levels of anemia. Iron studies are normal. • Severe forms of thalassemia may be confused with other hemoglobinopathies. • The diagnosis is made by hemoglobin electrophoresis.

49. The ThalassemiasEssentials of Diagnosis • Microcytosis out of proportion to the degree of anemia. • Positive family history or lifelong personal history of microcytic anemia. • Abnormal red blood cell morphology with microcytes, acanthocytes, and target cells. • In -thalassemia, elevated levels of hemoglobin A2 or F.

50. Anaemia of chronic disorders (ACD) • This is the rather unsatisfactory phrase used to cover the most common of the normochromic, normocytic anaemias, namely, those found in association with chronic infection, all forms of inflammatory diseases, and in malignant disease. It is very important for clinicians to be able to identify the main features of this type of anaemia. • Although it may be extremely mild and asymptomatic, the presence of this blood picture should always alert the clinician to the possibility of there being a serious underlying disease.