Classification and Management of Anaemias

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Microcytic Anaemia

Iron deficiency
Thalassaemia trait
Chronic disease/inflammation
Lead poisoning
Sideroblastic anaemias
Copper deficiency

Normocytic Anaemia

Membranopathies (spherocytosis, elliptocytosis, ovalocytosis)
Enzymopathies (G6PD, PK deficiencies)
Haemoglobinopathies(HBSS, SC)
Chronic disease/inflammation
Malignancy - leukaemia
Chronic renal failure
Acute bleeding
Antibody mediated haemolysis
Dyserythropoietic Anaemia
Haemophagocytic syndrome
Hypersplenism
Microangiopathy (HUS, TTP, DIC, Kasabach-Merritt)

Macrocytic Anaemia

Folate deficiency
Vitamin B12 deficiency
Acquired aplastic anaemia
Congenital aplastic anaemia (Diamond-Blackfan, Fanconi anaemia, Pearson syndrome)
Drug induced
Trisomy 21
Hypothyroidism
Oroticaciduria
Dyserythropoietic anaemia

Morphological abnormalities of RBCs

Decreased RBCs production
Increased RBC destruction
Blood loss

NB: Absolute reticulocyte count and reticulocyte percentage can help to distinguish the causes (1% and 25000-75000/mm3)

This is the most common micronutrient deficiency in the world.

It is estimated that 30% of the global population has iron-deficiency anaemia, and most of them live in developing countries.

Majority result from inadequate intake of dietary iron, but loss of iron through haemorrhage and hookworm infestation can also cause it.

Nutritional iron deficiency is more common between 6 and 24 months of life.

Aetiology

Low birth weight
Perinatal blood loss
Early clamping of umbilical cord
Consumption of cow’s milk
Gastrointestinal bleeding: PUD, Meckel diverticulum, polyp, haemangioma, IBD
Infestation by hook worm, Trichuris tricuria, plasmodium, H. pylori

Clinical features

Mostly asymptomatic
Pallor- palms, palmar crease, nail beds, conjuctivae.
Irritability
Anorexia
Lethargy
Systolic flow murmur
Tachycardia
High output cardiac failure
Neurocognitive impairment
Pica – desire to ingest nonnutritive substances, may lead to plumbism (lead ingestion)
Pagophagia- desire to ingest ice

Laboratory findings

↓serum ferritin
↓serum iron
↑serum Transferin
↓Transferin saturation
↑Free erythrocyte protoporphyrins
↑RDW (variation in red cell sizes)
↓MCV, ↓MCH
↓RBC count, normal WBC count, normal/ ↑platelets
Blood smear shows hypochromic, microcytic anaemia, elliptocytic or cigar-shaped red cells.
Stool for occult blood

Treatment

The regular response of iron-deficiency anaemia to adequate amounts of iron is a critical diagnostic and therapeutic feature.

Oral ferrous sulfate 3-6mg/kg/day.

Parenteral iron in malabsorption or poor compliance to oral iron.

Treatment should be continued 2-3 months after haematologic values normalize.

Blood transfusion in heart failure.

Response to iron therapy in IDA

12-24 hour Replacement of intracellular iron enzymes; subjective improvement; decreased irritability; increased appetite

36-48 hour Initial bone marrow response; erythroid hyperplasia

48-72 hour Reticulocytosis, peaking at 5-7 days

4-30 days Increase in hemoglobin level

1-3 month Repletion of stores

ACD is found in conditions where there is ongoing immune activation.

It occurs in a wide a range of disorders including infections, malignancies, CKD, autoimmunity, and graft-versus-host disease.

ACD is typically a mild to moderate normocytic, normochromic anaemia.

Aetiology

↓ Red cell life span- ↑interleukin-1, ↑ macrophage phagocytosis
Impaired erythropoiesis- cytokine-driven, bone marrow suppression
↑ Uptake of iron in the reticuloendothelial system- ↑ hepcidin synthesis

Clinical features

Signs and symptoms of underlying disorder.
Mild to moderate anaemia

Laboratory findings

↓Hb concentration- 6-9mg/dl
Normochromic, normocytic anaemia on blood smear.
Absolute reticulocyte count- normal/↓, leucocytosis.
↓serum iron, ↓/normal serum transferrin, ↑serum ferritin

Treatment

Treatment of underlying cause
Recombinant human erythropoietin (EPO)
Iron therapy
Blood transfusion

A common cause of haemolysis and haemolytic anaemia.

Prevalence is 1 in 5000

Most common inherited abnormality of the RBC membrane.

Aetiology

Usually A.D, less commonly A.R
Abnormality in cytoskeletal proteins- spectrin, ankyrin, band 3, protein 4.2
Destruction of spherocytic RBCs in the spleen.

Clinical features

Neonatal haemolytic anaemia and jaundice
May be asymptomatic
Pallor, fatigue, exercise intolerance
Splenomegaly, marrow hyperplasia (frontal bossing)
Gall stone formation
Aplastic crisis
High-output heart failure

Laboratory findings

Reticulocyte percentage 10%, hyperbilurubinaemia.
Normal MCV, ↑MCHC
Blood smear show spherocytes
↓haptoglobin
Gall stones seen on abd USS
Osmotic fragility test
Gel electrophoresis

Treatment

Phototherapy and EBT in the neonatal period.
Folate suplementation
Splenectomy
Cholecystectomy for gall stones

It is the most frequent disease involving enzymes of the hexose monophosphate pathway.

Inherited as X.R

An example of a balanced polymorphism

Aetiology

G6PD catalyzes G-6-P→ 6phosphogluconic acid.
Generates NADPH that keeps GSH in the reduced state.
GSH is an antioxidant
Variants: G6PD A-, G6PD B-, G6PD canton

Agents precipitating haemolysis in G6PD

Medications

Antibacterials

Sulfonamides
Dapsone
Trimethoprim-sulfamethoxazole
Nalidixic acid
Chloramphenicol
Nitrofurantoin

Antimalarials

Primaquine
Pamaquine
Chloroquine
Quinacrine
Antihelminths
β-Naphthol
Stibophen
Niridazole

Others

Acetanilide
Vitamin K analogs
Methylene blue
Toluidine blue
Probenecid
Dimercaprol
Acetylsalicylic acid
Phenazopyridine
Rasburicase

Chemicals

Phenylhydrazine
Benzene
Naphthalene (moth balls)
2, 4, 6-Trinitrotoluene

Illness

Diabetic acidosis
Hepatitis
Sepsis

Clinical features

Severe hyperbilirubinaemia and kernicterus in the neonates.
Most are asymptomatic unless triggered by agents.
Passage of dark urine, jaundice, pallor
Ingestion of fava beans (favism)

Laboratory findings

↓haemoglobin, ↓haematocrit
↓haptoglobin
Haemoglobinuria
Heinz bodies
↓G6PD activity in RBCs- methylene blue decolorization

Treatment

Blood transfusion

Remove precipitant

Folates are essential for DNA replication and cellular proliferation.

Dietary sources- green vegetables, fruits, animal liver/kidney.

Megaloblastic anaemia from folate deficiency is rare, but peak at 4-7months of age

Aetiology

Inadequate intake- malnutrition, increased requirement in haemolysis

Decrease folate absorption- malabsorption from chronic diarrhoea, celiac disease, enteroenteric fistulas; intestinal surgeries; anticonvulsants (e.g phenytoin, primidone, phenobarbital)

Abnormal folate transport and metabolism- hereditary folate malabsorption

Clinical features

Pallor
Irritability
Chronic diarrhoea
Poor weight gain
Hemorrhages from thrombocytopenia
Severe infections
Cognitive delays
Congenital folate malabsorption may be associated with hypogammaglobuliaemia

Laboratory findings

Macrocytic anaemia (MCV >100fl)
Variation in RBC shapes and sizes
↓reticulocyte count
Megaloblastic nucleated RBCs seen in peripheral blood
Neutropenia
Thrombocytopenia
Large neutrophils with hypersegmented nuclei
Hypercellular marrow
Serum folate <3ng/ml
↑lactate dyhydrogenase

note

Laboratory Findings

The bone marrow is hypercellular because of erythroid hyperplasia, and megaloblastic changes are prominent.

Large, abnormal neutrophilic forms (giant metamyelocytes) with cytoplasmic vacuolation are also seen.

Normal serum folic acid levels are 5-20 ng/mL; with deficiency, levels are <3 ng/mL. Levels of RBC folate are a better indicator of chronic deficiency. The normal RBC folate level is 150-600 ng/mL of packed cells. Levels of iron and vitamin B12 in serum usually are normal or elevated. Serum activity of lactate dehydrogenase, a marker of ineffective erythropoiesis, is markedly elevated.

Treatment

Folate therapy- 0.5-1mg/day orally or parenterally for 3-4 weeks

Blood transfusion in severe anaemia

Is a water-soluble vitamin

It is essential for methylation of homocysteine to methionine (via methionine synthase) and conversion of methyl-malonylcoenzyme A (CoA) to succinyl CoA (via l-methyl-malonyl-CoA mutase).

These reactions are critical to DNA, RNA and protein syntesis

Sources- animal products including meat, eggs, fish, and milk

Cobalamin is synthesized exclusively by microorganisms and humans must rely on dietary sources (animal products including meat, eggs, fish, and milk) for their needs.

Aetiology

Inadequate dietary intake- maternal deficiency, gastric bypass surgery, proton pump inhibitors, vegetarian diet.

Impaired absorption- gastric surgery, inhibition of gastric acid secretion, pancreatic insufficiency, NEC, IBD, celiac disease, surgical removal of terminal ileum, fish tapeworm infestation, hereditary IF deficiency, pernicious anaemia.

Absence of transport protein

Inborn error of metabolism of cobalamin

Fish tapeworm— Diphyllobothrium latum