ANAEMIA

PRESENTED BY ASHISH KOSHY MATHEW

INTRODUCTION
DEFINITION:-

Anaemias are group of diseases characterized by a decrease in either hemoglobin or RBC that reduces the oxygen carrying capacity of blood.

WHOMales Hb less than 13g/dL Females Hb less than 12g/dL

EPIDEMIOLOGY
Around 30% of the total world population is anaemic. 600million people have iron deficiency. 50% of pregnant women. 40% of infants. In Britain, 14% of women aged 55-64 yrs, 3% of men aged 35-64 yrs.

ETIOLOGY
Anaemia results from 2 different mechanisms:Reduced haemoglobin synthesis- due to lack of nutrient or bone marrow failure. Increased haemoglobin loss -due to haemorrhage(red cell loss)/haemolysis(red cell destruction).

NORMAL ERYTHROPOIESIS
PLURIPOTENT STEM CELL

ERYTHROID BURST FORMING UNIT(BFU-E)

ERYTHROID COLONY FORMING UNIT (CFU-E)

PROERYTHROBLAST

BASOPHILIC ERYTHROBLAST

POLYCHROMATIC ERYTHROBLAST

PYKNOTIC ERYTHROBLAST

BONE MARROW RETICULOCYTE

MATURE ERYTHRO CYTE

PERIPHERAL RETICULOCYTE

CLASSIFICATION
MORPHOLOGY
1.MACROCYTIC ANAEMIAS
2. MICROCYTIC, HYPOCHROMIC ANAEMIA 3. NORMOCYTIC ANAEMIA 4.ANAEMIA OF CHRONIC DISEASE

ETIOLOGY
1. DEFICIENCY 2. CENTRAL- CAUSED BY IMPAIRED BONE MARROW FUNCTION 3. PERIPHERAL

PATHOPHYSIOLOGY
1. EXCESSIVE BLOOD LOSS. 2. CHRONIC HAEMORRHAGE. 3. EXCESSIVE RBC DESTRUCTION. 4. INADEQUATE PRODUCTION OF MATURE RBC

INVESTIGATIONS
HEMOGLOBIN HEMOTOCRIT RBC INDICES TOTAL IRON BINDING CAPACITY VITAMIN B12 & FOLATE LEVEL HOMO CYSTEINE

FERRITIN LEVELS METHYL MALONIC ACID SCHILLINGS TEST BONE MARROW TESTING

IRON DEFICIENCY ANEMIA

Epidemiology Common form High prevalence in developing countries. Present in about 20% of the worlds population. Women of child bearing age , adult males.
Etiology Iron deficiency negative iron balance Dietary factors Rheumatoid arthiritis Blood donation Mensturatrion GI bleeding Medical history

PATHOPHYSIOLOGY
Mismatch btwn bodys iron requirements and iron absorption. Varies with age. Absorbed mainly from duodenum. Drugs and some vegetables form complexes with iron in GIT reducing the absorption of iron. Iron bound to haem is better absorbed. Main causes are malnutrition ,hook worms and high fatty food .

SIGNS AND SYMPTOMS

Pale

skin Painless glossitis Angular stomatitis Koilonychia Dysphagia Pica Tachycardia Palpitation

INVESTIGATIONS
Aim to correct anemia and replenish iron stores. Low ferritin level:10 12 g/l. Low transferrin saturation value below 15%. TIBC greater than 400g%. Blood smear: hypochromic , pencil shaped cells, nucleated RBCs. Bone marrow examination. Decreased hemosiderin. Low hematocrit and Hb.

TREATMENT
Prophylaxis in pregnant ladies. Standard treatment:ferrous sulphate 200 mg 3 times a day for 6 months. Parenteral iron : reserved for patients who fail on oral therapy. Maximum individual dose:intravenous iron sucrose 100mg. Treatment consists of dietary supplementation and administration of iron preparations. Dose depends on patients ability to tolerate iron.

IRON PREPARATIONS
TABLETS ORAL LIQUIDS
Ferrous

Ferrous sulphate 200mg Ferrous gluconate 300mg Ferrous fumarate 200mg Ferrous polysaccharide 200mg

fumarate

140mg Ferrous glycine sulphate 141mg Sodium feredetate 190mg

PATIENT CARE
Advise

patients to take iron products with or after meals to reduce nausea. Patient should be told that faeces will become darker with melena. Length of treatment should be discussed and tell that it will take time for replenishment.

SIDEROBLASTIC
Group

ANAEMIA

of condn diagnosed by finding ring sideroblast in bone marrow. ETIOLOGY:Both hereditary & acquired forms. Hereditary through X chromosome. Acquired include idiopathic , myeloproliferative disorders. Impaired haem synthesis. Alcoholics

ACQUIRED SIDEROBLASTIC
DISORDERS Myeloma.

ANAEMIA

DRUGS & TOXINS

Myeloid Leukaemia.
Collagen diseases.

Alcohol. Cycloserine. Copper deficiency. Isoniazid. Penicillamine. Pyrazinamide. Progesterone.

PATHOPHYSIOLOGY
Erythroblast with iron granules around cell nucleus known as RING SIDEROBLAST is found in bone marrow-due to deficiency in ALAS. ALAS ,a mitochondrial enzyme -1st step in haem synthesis.(require pyridoxine as cofactor).

INVESTIGATION

High serum iron & ferritin. Presence of sideroblast in bone marrrow. Increased iron stores.

TREATMENT
Large doses of pyridoxine-200mg daily. Chelating agent Desferrioxamine i.v or s/c inj. Oral vitamin C. Blood tranfusion. PATIENT CARE Pyridoxine takes several months for improvement. Not to purchase OTC iron or vitamin supplements without medical advice.

ANEMIA OF CHRONIC DISEASE

ETIOLOGY
CHRONIC INFECTIONS TB Chronic lung infections HIV MALIGNANCIES Carcinoma Lymphoma Leukemia CHRONIC INFLAMMATION Rheumatoid arthritis SLE Gout CILD LESS COMMON CAUSES ALD CHF

PATHOPHYSIOLOGY
Associated with infections , inflammatory, hepatic diseases or neoplastic diseases lasting more than 1 or 2 months. RBCs - shortened life span & bone marrows capacity to respond to EPOinadequate. IL-1,gamma- interferon & TNF released inhibit production of EPO or RBC & their action.

INVESTIGATION

Decreased serum iron level. Serum ferritin level normal or increased, iron binding capacity is decreased. ACD is normocytic & can be severe.

Hematocrits as low as 25%.

SIGNS & SYMPTOMS

Fatigue , breathlessness , swollen feet ,chest pain & decreased mental acuity. IDA & Folic acid deficiency. TREATMENT Resolution of the underlying process. Transfusions of RBCs are effective. Exogenous EPO(Recombinant human EPO). Epoetin alfa-150 units/Kg 3 times s/c weekly. Patients ; hematocrit 38% -improvement in energy level. Oral iron supplementationis not usually done.

MEGALOBLASTIC

ANEMIA

MEGALOBLASTIC ANEMIA
Macrocytic anaemia Abnormality in maturation of haematopoetic cells in bone marrow. 2 major causes: Folate deficiency Vitamin B12 deficiency

VITAMIN B12 DEFICIENCY ANEMIA

Epidemiology Strict vegans Total gastrectomy 6% of partial gastrectomy. Etiology Inadequate intake. Decreased absorption of vitb12. Overgrowth of bacteria. Decrease in production of IF.

PATHOPHYSIOLOGY
Absorption is an active process. Vitb12 + glycoprotein = IF. IF protects vitb12 from breakdown. Specific receptors in distal ileum for IFVitb12 complex. IF produced by gastric parietal cells. Total gastrectomy.

SIGNS & SYMPTOMS

Pale & mildly icteric. Gastric mucosal atrophy. Neuropsychiatric abnormalities. Paresthesias, ataxia, glossitis, muscle weakness, dysphagia, anorexia, irritability, dementia, psychosis. Macrocytosis, poikilocytosis & mild thrombocytopenia. Enlarged spleen, slight fever, mild jaundice & neuropathy.

INVESTIGATION
Serum vitb12 level. Schilling test. Peripheral blood smear. Serum lactate dehydrogenase. Indirect bilirubin level. Reticulocyte count. Bone marrow examination.

TREATMENT
Lifelong replacement therapy. Therapy for underlying disorder. Emergency transfusion with packed cells. Diuretics. Standard treatment: hydroxocobalamin 1mg IM 5 times 3 day intervals, followed by maintenance dose : 1 mg IM every 3 months. Potassium supplements. Oral dose: 1 mg.

PATIENT CARE
Feel better very shortly after first injection. Feel sore tongue . Regular injections every 3 months.

FOLATE DEFICIENCY ANEMIA

ETIOLOGY
Causes include inadequate intake,decreased absorption, hyperutilization & inadequate utilization. Common in elderly patients, alcoholics, poverty stricken & chronic ill patients. Hyper utilization is seen in pregnancy, hemolytic anaemia, myelofibrosis,malignancy, chron`s disease, psoriasis

DRUGS CAUSING FOLATE DEFICIENCY

Malabsorption Phenytoin Barbiturates Sulfasalazine Colestyramine Oral contraceptives. Impaired metabolism Methotrexate Pyrimethamine Triamterene Pentamidine Trimethoprim

Dietary folate

Gut

Folate monoglutamate
PATHOPHYSIOLOGY

Methyltetrahydrofolate monoglutamate

Bone marrow Tetrahydrofolate monoglutamate

Tetrahydrofolate polyglutamate

Bone marrow Folate coenzym e Dihydrofolate polyglutamate

SIGNS & SYMPTOMS

Chronic

folate deficiency: thrombosis, depression & neoplasia.

INVESTIGATION
Decrease in serum folate level : <3 ng/ml. Decrease in RBC folate level : <150 ng/ml.

Peripheral blood smear.

TREATMENT
Duration of treatment depends on cause of deficiency. Normal daily requirement : 100 g a day. Usual treatment doses : 5 15 mg a day for 4 months. Long term treatment in case of chronic hemolytic states, refractory malabsorption syndrome and myelofibrosis. Low dose folate therapy (500 g daily) in case of anticonvulsant therapy.

PREGNANCY
Increase in pregnancy, higher in twin pregnancies. Prophylaxis with folate (350 500g) daily in combinaton with iron. Higher doses in women with neural tube defects 5mg daily.

PATIENT CARE
Appropriate nutritional advice. Blood picture takes some days to be normal. Even though underlying cause is treated, patient should be advised to take folic acid for 4 months.

PERNICIOUS ANEMIA

EPIDEMIOLOGY

Found most commonly in N European descent. In Britain, incidence is about 120/100,000. Higher in Scotland. A disease of elderly mostly at age 60. ETIOLOGY Inadequate intake. Malabsorption.

PATHOPHYSIOLOGY
Autoimmune

in origin. Gastric parietal cell antibodies are found in 90% of PA patients. No IF secretion and gastric atrophy is seen in PA patients.
INVESTIGATION
Parietal

cell antibodies are found.

HEMOLYTIC ANEMIA

 Reduced

lifespan of erythrocytes.

Rate

of destruction of erythrocytes exceeds rate of production anemia results. of HA with both genetic and acquired disorders.

Wide

COMMON CLASSES OF HEMOLYTIC ANEMIA

Genetic disorders Membrane

Extrinsic Immune

Hereditary spherocytosis ovalcytosis

Rh incompatability Autoimmune

Hb
Sickle cell anemia

Non immune
Infections Drugs & chemicals. Hypersplenism.

Thalassemia Energy pathways

G6PD

SIGNS & SYMPTOMS

Acute:

malaise, fever,abdominal pain,dark urine & jaundice.

Increased reticulocyte count. Decreased haptoglobin LDH increases Increase in indirect bilirubin.

INVESTIGATION:

TREATMENT

Steroids

& immunosuppressive agents.

Splenectomy

Manage

the underlying cause.

THALASSAEMIA
EPIDEMIOLOGY Populations from Mediterranean , North & West Africa ,middle east & Indian Subcontinent. Severe homozygotes lead to death in utero or infancy. ETIOLOGY Homozygotes are severely affected. No - chain prodn(0 thalassaemia). Reduced prodn of a chain(+ thalassaemia).

PATHOPHYSIOLOGY

In thalassaemias , reduced or absent prodn of the globin chain excess of chain ineffective erythropoiesis.
In thalassaemias , deficiency of chains excess of or chains- erythropoiesis is less affected but the Hb produced is unstable.

SIGNS & SYMPTOMS

Increase in erythropoietin production. Bone deformity & growth retardation.

Spleen become enlarged.

INVESTIGATION Electrophoresis.

TREATMENT

Transfusion from an early age. Desferrioxamine and Deferiprone. Splenectomy. Combination of drugs hydroxy urea & erythropoietin. Switching the bone marrow to the production of fetal Hb.

G6PD DEFICIENCY
EPIDEMIOLOGY 300 million people are affected. 15% black Americans, More severe form Mediterranean variant. ETIOLOGY Glutathione production

PATHOPHYSIOLOGY
Deficiency in G6PD decreases prodn of NADPH ,needed to keep glutathione in a reduced form. If erythrocytes are exposed to an oxidizing agent, Hb becomes oxidised & forms Heinz bodies. Cell membrane is damaged & red cells hemolyze. INVESTIGATION: Measuring G6PD activity.

DRUGS CAUSING HEMOLYSIS

ALL

VARIANTS Ciprofloxacin Dapsone Primaquine Naldixic acid sulphonamides

SEVERE

VARIANTS Aspirin Chloramphenicol Chloroquine Probenicid Quinidine

TREATMENT
Causative

oxidizing agent should be stopped. General supportive measures. Patient kept hydrated. Blood transfusion. Vitamin E - antioxidant. Avoid precipitating factors.

PATIENT CARE Little drug specific advice can be given. List of drugs to avoid given.

Epidemiology Found in ethnic gps (tropical regions) In UK app 5000 people from Afro Caribbean population.

Etiology Different form of Hb HbA(normal Hb) & HbS(sickle cell disease). Valine for glutamic acid as 6th AA. Sickle cell trait is where a person is a carrier of the gene.

PATHOPHYSIOLOGY
Red cells with Hbs damaged leads to intracellular dehydration. Patients blood deoxygenated polymerisation of Hbs occurs forming semisolid gel. These lead to formation of crescent shaped cells known as sickle cells.

SIGNS & SYMPTOMS

Chronic anemia, arthralgia, anorexia, fatigue & splenomegaly. Crisis . Infarction of large bones with severe pain.

INVESTIGATION
Abnormal Hb : electrophoresis Proportion of Hbs.

Serum ferritin.

TREATMENT
Penicillin 250mg twice or a day for adults. Erythromycin for penicillin allergy.

Pneumococcal & haemophilus vaccine.

Transfusions. Strong opioids.

PATIENT CARE
Patients must be encouraged to take prophylactic penicillin & folic acid therapy regularly.

Opioid addiction should be considered.

Effective analgesia for pain should be suggested.

REFERENCE
1.

2.

A PATHOPHYSIOLOGIC APPROACH TO DISEASE BY JOSEPH T DIPIRO,1729 1744. CLINICAL PHARMACY & THERAPEUTICS BY ROGER WALKER & CLIVE EDWARDS,THIRD EDITION ,725 739.