Iron deficiency anemia and anemia of chronic disease

Dr. Mousa Qasim Hussein Assistant professor Consultant physician

12-10-2015

ANAEMIAS

Around 30% of the total world population is anaemic and half of these, some 600 million people, have iron deficiency.

Iron deficiency anaemia

This occurs when iron losses or physiological requirements exceed absorption.


Without iron, cells lose their capacity for electron transport and energy metabolism. In erythroid cells, hemoglobin synthesis is impaired, resulting in anemia and reduced O2 delivery to tissue.

Causes of Iron Deficiency

1-Physiological demands
At times of rapid growth, such as infancy and puberty, iron demands increase and may outstrip absorption. In pregnancy, iron is diverted to the fetus, the placenta and the increased maternal red cell mass, and is lost with bleeding at parturition


2-Blood loss
The most common explanation in men and post-menopausal women is gastrointestinal blood loss . occult gastric or colorectal malignancy gastritis, peptic ulceration inflammatory bowel disease diverticulitis, polyps and angiodysplastic lesions. World-wide, hookworm and schistosomiasis are the most common causes of gut blood loss .

Gastrointestinal blood loss may be exacerbated by the chronic use of aspirin non-steroidal anti-inflammatory drugs (NSAIDs), which cause intestinal erosions and impair platelet function.

In women of child-bearing age, menstrual blood loss, pregnancy breastfeeding contribute to iron deficiency by depleting iron store. Very rarely, chronic haemoptysis or haematuria may cause iron deficiency.

3-Malabsorption

A- Gastric acid is required to release iron from food and helps to keep iron in the soluble ferrous state . Hypochlorhydria in the elderly or that due to drugs such as proton pump inhibitors may contribute to the lack of iron availability from the diet. B- previous gastric surgery. C-Iron is absorbed actively in the upper small intestine and hence can be affected by coeliac disease

Daily requirement: -infants, children = 1-2mg/day -adult male = 1mg/day -premenopausal female = 2mg/day -pregnant woman = 3mg/day, increased in the last two trimesters to 5-6mg/day. Iron absorption : by the proximal small intestine, foods contain certain compounds as phosphates & phagtates inhibit absorption while ascorbic acid can promote iron absorption.


Stages of Iron Deficiency The progression to iron deficiency can be divided into three stages . The first stage is negative iron balance(Pre latent ID): in which the demands for (or losses of) iron exceed the body's ability to absorb iron from the diet. This stage results from a number of physiologic mechanisms, including -blood loss -pregnancy (in which the demands for red cell production by the fetus outstrip the mother's ability to provide iron) -rapid growth spurts in the adolescent, -inadequate dietary iron intake.

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The second stage is iron-deficient erythtopoiesis(Latent ID ): When iron stores become depleted, the serum iron begins to fall. Gradually, the TIBC increases, . By definition, marrow iron stores are absent when the serum ferritin level is <15 micro. g/L. As long as the serum iron remains within the normal range, hemoglobin synthesis is unaffected despite the dwindling iron stores. Once the transferrin saturation falls to 15–20%, hemoglobin synthesis becomes impaired. .

the third stage isiron-deficiency anemia: Careful evaluation of the peripheral blood smear reveals the first appearance of microcytic cells, and if the laboratory technology is available, one finds hypochromic reticulocytes in circulation. Gradually, the hemoglobin and hematocrit begin to fall, reflecting iron-deficiency anemia


Clinical features: 1.clinical features of anemia(fatigue.pallor and reduce exercise capacity). 2.clinical features of iron deficiency: *spoon shaped nails (koilonychias) *angular chilitis (painful hacks at the corner of the mouth) *atrophic glossitis (pale, smooth tongue) *Paterson Kelly or Plummer Vinson syndrome: Post-cricoids web is a rare complication of IDA.


Investigations A/ confirmation of iron deficiency: 1. Serum iron: normal range for serum irons (50-150 micro.g/dl). It is very low in acute phase response bat increase in liver disease & hemolysis. 2. Total iron binding capacity (TIBC): measure of the total iron bond to transferrin (plasma Glycoprotein that binds two atoms of iron). Normal TIBC (300-360micro.g/dl). Trasferrin saturation : (SI/TIBC=%saturation) Normal between 30-50% IDA level below 20% Dangerous iron overload more than 50-60%

3-Plasma ferritin is a measure of iron stores in tissues and is the best single test to confirm iron deficiency . It is a very specific test; a subnormal level is due to iron deficiency, hypothyroidism or vitamin C deficiency. Levels can be raised by liver disease and in an acute phase response. Adult males have serum ferritin values averaging 100 micro.g./L , while adult females have levels averaging 30 micro.gram/L.

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4. Serum transferrin Receptors: level correlate with the level of erythroid precursor proliferation & adequately of iron supply to the marrow. Normal level 4-9micro.g/L by immunoassay, level increased in IDA. 5. Red cell protoprophyrin level: is the molecule made in mitochondria to which iron is added to form Haem. Normal value below (30micro,g/dl). Higher than normal level indicate an inadequate iron supply. 6. Marrow iron stores: reticuloendothelial cell iron stores can be estimated from the Prussian blue stain of a marrow aspirated or biopsy specimen.

Sever iron deficiency anaemia

B/Investigation of the cause: Depend on (age, sex, history & clinical findings). e.g.: men over 40, post-menopausal women with normal diet upper &lower GI tract should be investigated by endoscopy & barium studies. If celiac disease is suspected serum anti-gliadin & anti-endomycin Ab & duodenal biopsy are indicated. In tropics stool, urine ex: for parasites.


Management: -depend on: 1. Aetiology of IDA. 2. Severity. 3. The ability of the patient to tolerate oral preparations. 4. if the patient has angina, heart failure or evidence of cerebral hypoxia. Treatment: 1. Treat the underlying cause (bleeding, malabsorption). 2. Blood transfusion: only for sever anemia, heart failure, angina or evidence of cerebral hypoxia. 3. Iron replacement:



*oral iron preparations: Ferrous sulphate 200mg 8 hourly (195mgof elemental iron per day) for 3-6 months to replete iron stores. If the patient intolerant of ferrous sulphate with dyspepsia & altered bowel habit so either decrease the dose to 200mg 12 hourly or change to ferrous gluconate 300mg 12 hourly (70mg of elemental iron per day). **delayed release preparations are not useful since they release iron beyond the upper small intestine where it can't be absorbed. Hb should be increased Ig/dl every 7-10 days & reticulocyte response will be evident by one week.


-failure to respond to treatment adequately: *non-compliance. *continued blood loss. *malabsorption *incorrect diagnosis. S.E: GI distress is form of abdominal pain, nausea, vomiting, constipation or diarrhea.


*parental iron therapy: -indications: 1. Oral preparation intolerance. 2. Non-compliance. 3. Malabsorption & chronic gut disease. 4. Patient receiving recombinant erythropoietin to guarantee adequate iron delivery to support erythroid precursor proliferation. .


o
. Iron dextran: 2 preparations are available: one containing 0.5% phenol for IM use & 2nd is phenol free for IM &IV use. We can administer a bolus IV injection of the total dose required to correct anemia. Calculated as: Body wt (Kg)*2.38(15-patient Hb g/dl) +500-1000mg (for stores) =total dose (mg). Better to dilute in 100-250ml of 0.9 NaCl solutions & administered over 30-90 min. If patient gives a history of past reaction to iron-dextran either immediate or late serum sickness like further exposure to iron dextran should be avoided.

ANAEMIA OF CHRONIC DISEASE

This is a common type of anaemia, particularly in hospital populations. Characteristic features: 1. It occurs in the setting of chronic infections, chronic inflammation or neoplasia. 2. The anaemia is not related to bleeding, haemolysis or marrow infiltration, 3. mild, in the range of 85-115 g/l, and is usually associated with a normal MCV (normocytic, normochromic), but up to 25% may have reduced MCV 4. The serum iron is low but iron stores are normal or increased, as indicated by the ferritin or stainable marrow iron.


Clinical features The clinical manifestations usually obscured by the clinical Features of the underlying disease. Moderate anaemia(Hb lessThan 10 g/dl) can exacerbate the symptom of ischemic heart disease or respiratory disease or contribute to fatigue or exertional intolerance. The diagnosis is based clinical features in conjugation with lab.Results.



Laboratory features The erythrocytes are normocytic and normochromic With increasing severity or duration can become Hypochromic and eventually microcytic anaemia The absolute reticulocyte count are either normal or Slightly elevated

Diagnosis and management

It is often difficult to distinguish ACD associated with a low MCV from iron deficiency. .Examination of the marrow may ultimately be required to assess iron stores directly A trial of oral iron can be given in difficult situations. A positive response occurs in true iron deficiency but not in ACD. Measures which reduce the severity of the underlying disorder generally help to improve the ACD.

Iron deficiency anaemia

↓ ↓ ↑ ↓ ↑ Anaemia of chronic disease
↑/Normal ↓ ↓ ↓ ↓/Normal Ferritin
Iron
TIBC
Transferrin saturation
Soluble transferrin receptor
Investigations to differentiate anaemia of chronic disease from iron deficiency anaemia


treatment of anaemia of chronic disease1-blood transfusion *indications:a- cardiac ischemiab –lack of response to other modalities*typical settingsHb less than 10g/dl Chest pain and ECG changes *risk and side effectsInfectionsVolume over loadreaction

2-Erythopoietin Indications *fatigue *exertional intolerance Typical setting *Hb lessthan 10g/dl *anemia symptoms Risk and side effects *Response takes several weeks. *may worsen outcome in some cancers. *Expensive


3- iron( oral and parantral) Indications Coexisting iron deficiency Resistance to erythropoietin* Typical settings *suspected or documented iron deficiency Risk and side effects Gastrointestinal (oral). Systemic and local reaction (parantral)