Presenting

MANAGEMENT OF

Symposium Medicus

- Batch roll nos. 120 to 140

Decrease in oxygen carrying capacity of blood characterized by number of RBCs below 4 million/cubic mm or content of haemoglobin less than 12gm/dL

ANAEMIA

HAEMORRHAGIC

DIETARY DEFICIANCY

APLASTIC

HEMOLYTIC

IRON DEFICIENCY

MEGALOBLASTIC

IRON PHYSIOLOGY

CAUSES OF IRON DEFICIENCY ANAEMIA

LOW DIETARY INTAKE IMPAIRED ABSORPTION INCREASED REQUIREMENT CHRONIC BLOOD LOSS

SIGNS AND SYMPTOMS

Signs and Symptoms

No symptoms if the anemia is mild. Most of the time, symptoms are mild at first and develop slowly. Symptoms may include: Irritability Fatigue Dyspnea during exercise Headaches Problems concentrating or thinking

As the anemia gets worse, symptoms may include: Blue color to the whites of the eyes Brittle nails Light-headedness when one stands up Pale skin color Shortness of breath Sore tongue

Symptoms of the conditions that cause iron deficiency anemia include: Dark, tar-colored stools or blood Heavy menstrual bleeding (women) Pain in the upper belly (from ulcers) Weight loss (in people with cancer)

LABORATORY INVESTIGATIONS OF ANAEMIA

1.INITIAL INVESTIGATIONS
HEMATOLOGY PROFILE (Complete blood count) MCV,MCH,MCHC are decreased MICROSCOPY Blood picture reveals microcytosis, hypochromia, anisocytosis, poikilocytosis, pencil cells and target cells Bone marrow findings show high cellularity, poorly haemoglobinised normoblast and absence of stainable iron SERUM FERRITIN levels are decreased(normal levels-30 to 400ng/ml in males and 15 to 200 ng/ml in females)

2.ADDITIONAL INVESTIGATIONS

SERUM IRON levels are decreased (normal levels 65-176micrograms/dl in men,50170micrograms/dl in women,100-250micrograms/dl in newborns and 50-120micrograms/dl in children)

TIBC (Total Iron Binding Capacity) is increased (normal-240 to 450micrograms/dl) TRANSFERRIN SATURATION is decreased (normal-20 to 50%)

NON PHARMACOLOGICAL TREATMENT

Dietary advice

To both anaemic and non-anaemic women. Vitamin C significantly enhances iron absorption from non-haem foods, the size of this effect increasing with the quantity of vitamin C in the meal. Germination and fermentation of cereals and legumes improve the bioavailability of non-haem iron by reducing the content of phytate. Tannins in tea and coffee inhibit iron absorption when consumed with a meal or shortly after.

Oral iron therapy

Oral iron therapy

Indication- women with mild to moderate deficiency with no absorption or compliance (or both) limiting factors Ferrous iron salts are the preparation of choice. Oral dose in case anaemia due to iron deficiency should be 100200mg of elemental iron daily. Doses not to be increased to avoid saturation of absorption and dose related side effects. Women should be counselled as to how to take oral iron supplements correctly. This should be with a source of vitamin C such as orange juice to maximise absorption. Consumption with meals may be necessary to avoid side effects. Other medications or antacids should not be taken at the same time.

When side effects appear affecting compliance, titration of dose to a level where side effects are acceptable or a trial of an alternative preparation may be necessary. Preparations with lower iron content should be tried. Enteric coated or sustained release preparations should be avoided as the majority of the iron is carried past the duodenum, limiting absorption. A repeat Hb at two weeks is required to assess response to treatment. The haemoglobin concentration should rise by approximately 20 g/l over 3-4 weeks. Once the Hb is in the normal range, treatment should be continued for a further 3 months and at least until 6 weeks postpartum to replenish iron stores.

Parenteral Iron Therapy

Parenteral Iron Therapy

Indications :

Deficiency is severe
Along with erythropoietin Failure to tolerate oral iron Failure to absorb oral iron Non-compliance to oral therapy Iron requirement = 4.4 x body weight (kg) x Hb deficit (g/dl)

Parenteral Iron Therapy

Preparations available for IM use: Iron-dextran (Imferon): 1.5 ml vial, 50 mg of elemental iron/ml Iron-sorbitol-citric acid complex (Jectocos):1.5 ml vial,50 mg of iron/ml IM injection : Common site : Gluteal region Technique: Z track Dose: After an initial test dose of 25 mg,100 mg is administered daily till calculated dose is attained.

Iron-dextran
High molecular weight Can be given i.m or i.v Not bound to transferrin Given i.m. 10-30% is locally bound Not excreted Given i.m. absorbed via lymphatics Taken up by macrophages

Iron-sorbitol-citric acid
Low molecular weight Can be given only i.m. Tends to saturate transferrin Not locally bound About 30% excreted in urine Absorbed directly into circulation Directly available

Parenteral Iron Therapy

Preparations available for IV use:

High molecular weight iron dextran (Imferon): 1-2 ml vial,50 mg iron/ml

Low molecular weight iron dextran (Cosmofer):

2 ml vial,50 mg iron/ml

Iron saccharate: 5 ml vial,20 mg of iron/ml Ferric gluconate: 5 ml vial,12.5 mg iron/ml

Parenteral Iron Therapy

IV injection:
After an initial dose of 0.5 ml given over a a period of 5-10 mins, 2 ml can be injected over 10 mins every day.

Alternatively the total calculated dose is diluted in 500 ml of glucose/saline solution & infused slowly over 6-8 hours.

Ferric gluconate or iron saccharose may be used in repeated boluses in the dose of 100-200 mg of elemental iron.

Management in pregnancy

 Full blood count taken at the booking appointment and at 28 weeks. Prophylaxis starting in 2nd trimester for all pregnant women with 30 mg oral elemental iron daily. Hb < 11g/dl up until 2 months or <10.5g/dl beyond 2 mths no anaemia Hb < 11g/dl up until 2 months or <10.5g/dl beyond 2 mths anemia trial of therapeutic iron replacement. In non-anaemic women also, who are at increased risk of iron depletion such as those with previous anaemia, multiple pregnancy, consecutive pregnancies with less than a years interval between and vegetarians, a serum ferritin should be considered. therapeutic iron replacement if ferritin is <3 g/dl. Secondary care if there are significant symptoms and/or severe anaemia (Hb<7g/dl) or advanced gestation (>8 mths) or if there is no rise in Hb at 2 weeks. Education and counseling

IRON TOXICITY

ADVERSE EFFECT OF ORAL IRON THERAPY BLACKENING OF TEETH AND FAECES DUE TOFORMATION OF IRON SULPHIDE SEVERE VOMITING ABDOMINAL PAIN HEMATEMESIS DIARRHOEA CARDIOVASCULAR COLLAPSE AND SHOCK SOME MAY DEVELOP JAUNDICE,HYPOGLYCEMIA AND CONVULSIONS SYMPTOMS BECOME EVIDENT AFTER 6HRS OF CONSUMPTION DOSES OF 1gm OR MORE OF FERROUS SULPHATE ARE CONSIDERED TOXIC IN CHILDREN

ADVERSE REACTION TO IM PREPARATION

LOCAL PAIN PERMANENT SKIN DISCOLOURATION REGIONAL LYMPHADENOPATHY MYALGIA ATHRALGIA TACHYCARDIA FLUSHING CIRCULATORY COLLAPSE HAEMOLYSIS SYSTEMIC TOXICITY MAY DEVELOP WITHIN 10MINS OF INJECTION

ADVERSE EFFECT OF I.V IRON THERAPY

SYSTEMIC REACTIONS SIMILAR TO IM iron SEVERE CHEST PAIN RESPIRATORY DISTRESS CIRCULATORY COLLAPSE EXTRAVASATION INTO SUBCUTANEOUS TISSUE CAN CAUSE ABSCESS FORMATION ANAPHYLACTOID REACTIONCAN OCCUR WITHIN FIRST FEW MINUTES OF ADMINISTRATION. THEREFORE TEST DOSE MUST BE GIVEN PRIOR TO STARTING THE TREATMENT

ADVERSE EFFECTS OF EXCESSIVE IRON SUPPLEMENTS

IRON POISONING MAY BE1]ACUTE IRON POISONING 2]CHRONIC IRON OVERLOAD Toxic dosage The amount of iron ingested may give a clue to potential toxicity. The therapeutic dose for iron deficiency anemia is 36 mg/kg/day. Toxic effects begin to occur at doses above 1020 mg/kg of elemental iron

CAUSESACCIDENTAL CONSUMPTION BY CHILDREN INTENTIONAL INGESTION BY ADULTS

SYMPTOMS BECOME EVIDENT AFTER 6HRS OF CONSUMPTION DOSES OF 1gm OR MORE OF FERROUS SULPHATE ARE CONSIDERED TOXIC IN CHILDREN

CHRONIC IRON OVERLOAD

SIGNS AND SYMPTOMS CORROSIVE TOXICITYIron is an extremely corrosive substance to the GI tract. It acts on the mucosal tissues and can manifest with nausea, vomiting, abdominal pain, hematemesis, and diarrhea; patients may become hypovolemic because of significant fluid and blood loss Cellular toxicity- Severe overdose causes impaired oxidative phosphorylation and mitochondrial dysfunction, which can result in cellular death. METABOLIC ACIDOSIS

TREATMENT OF IRON POISONING

MILK AND EGG YOLK MIXTURE-TO BIND IRON Gastric lavage with water containing desferroxamine or if not available then with calcium disodium edetate DESFERRIOXAMINE 1-2gm IM IS ADMINISTERED DOC for iron intoxication. DESFERRIOXAMINE Approximately 8 mg of iron is bound by 100 mg of deferoxamine. Readily chelates iron from ferritin and hemosiderin but not transferrin Most effective when administered continuously by infusion Iv infusion 10-15mg/kg/hr to a maximum of of 80mg/kg in 24hr

Early replacement of body fluids and electrolytes using isotonic saline,correction of metabolic acidosis and hypotension by using ringer lactate and vasopressor diazepam

VITAMIN B12

HISTORY

Addison described anaemia not responding to Fe as PERNICIOUS ANAEMIA (PERNICIOUS for INCURABLE and DEADLY) and also its relation to atrophy of gastric mucosa. Minot and Murphy-included liver in diet of such patients-received Nobel prize. Castles hypothesis-an extrinsic factor(in diet) combines with intrinsic factor(produced by stomach)gives rise to haemopoietic principle.

Vitamin B12

Water soluble,thermostable,red crystals. Synthesized in nature only by microorganisms; plants and animals get from them. DIETARY SOURCES-Liver,egg yolk,kidney,cheese. *ONLY vegetable source-LEGUMES(pulses). *Vit. B12- synthesized by colonic microflora but not available for absorption in man. COMMERCIAL SOURCE- Strep. Griseus. Daily req.-1 -3 micro gm. In pregnancy and lactation-35 micro gm.

METABOLIC FUNCTIONS

1. 2. 3. 4. 5.

Active coenzyme forms-deoxyadenosyl cobalamin(DAB12) and Methyl cobalamin(methyl B12). Conversion of homocysteine to methionine. Purine and pyrimidine synthesis. Propionic acid metabolism. Synthesis of phospholipid and myelin. Essential for cell growth and multiplication.

Methionine Malonic acid

DAB12

S-adenosyl methionate Succinic acid

DAB12

UTILISATION 0F VIT.B12

TRANSPORTED-In combination with transcobalamin II. Congenital absence or abnormal proteins(like TCI and TCIII)-interfere with delivery of vit.B12 to tissues. Not degraded in body. Excreted in bile.Significant Enterohepatic circulation takes place.

CAUSES OF DEFICIENCY
1.

2. 3. 4. 5. 6.

Addisonian pernicious anaemia- Auto Immune disorder Gastric mucosal damage Malabsorption Blind loop syndrome Nutritional deficiency Increase in demand in pregnancy and infancy

MANIFESTATIONS OF DEFICIENCY
1.

2.

3.

MEGALOBLASTIC ANAEMIA- First manifestation-with hypersegmented neutrophil,giant platelets. Glossitis and G.I. disturbances: damage to epithelial structures. Neurological: a) Subacute Combined Degeneration of Spinal Cord b) Peripheral neuritis c) Mental changes

PREPARATIONS DOSE AND ADMINISTRATION

1.

2.
3. 4.

5.
6.

7.
8.

CYANACOBALAMIN. HYDROXOCOBALAMIN. METHYLCOBALAMIN. METHYL B12- Required for integrity of myelin.Dose 1.5mg/day. When deficiency due to decrease in Intrinsic factor-i.m. or s.c. but not i.v. Initially- 30-100 micro gm/ day for 10 days,then 100 micro gm weekly then monthly. Neuro complications 500-1000micro gm/ day. Prophylactic-3-10 micro gm/day.

USES OF VIT. B12

1.

2.
3. 4.

TREATMENT of VIT. B12 DEFICIENCY. PROPHYLAXIS of VIT. B12 DEFICIENCY. Neuropathies and psychiatric disorders. Tobacco amblyopia ADVERSE EFFECTSa) Large doses are also safe. b) Allergic reactions due to injection.

FOLIC ACID DEFICIENCY ANAEMIA

FOLIC ACID : PTERIDINE + PABA + GLUTAMATE

DIETARY SOURCES : yeast, liver, kidney, green leafy vegetables ( spinach ), egg, meat, milk

DAILY REQUIREMENT : 150-200 microgram in children 400 microgram in adults 600 microgram or greater in pregnancy 500 microgram in lactation Hepatic stores of folate contain 15-20 mg of folate, which is very less and can be easily exhausted within 3-4 months of stopping oral folate administration

NORMAL SERUM FOLATE LEVELS : 2.7-17 ng/ml UTILISATION : Present in foods as polyglutamates of n5 methyl THFA Absorbed in upper part of jejunum after converting polyglutamate residues to monoglutamate residues

Absorbed in this form by active and passive transport processes and demethylated in the cells to THFA by vit b12

 1. 2. 3. 4.

METABOLIC FUNCTIONS : active form : THFA Conversion of homocysteine to methionine Conversion of d ump to d TMP Conversion of serine to glycine Purine synthesis which requires formyl and methenyl THFA histidine metabolism for mediating formimino group transfer

FOLIC ACID DEFICIENCY IS SEEN IN : Chronic alcoholic patients Liver disease Pregnant women Hemolytic anaemia Malabsorbtion syndrome Renal dialysis patients Drugs like methotrexate, trimethoprim, pyrimethamine, phenytoin

PREPARATIONS AND DOSE : preparations of 2 compounds available:

FOLIC ACID : FOLVITE , FOLITAB 5mg TABS

FOLINIC ACID : CALCIUM LEUCOVORIN, FASTOVORIN, RECOVORIN

PARENTERAL ADM IS RARELY NECESSARY AS ORAL FOLIC ACID ID=S WELL ABSORBED EVEN IN PATIENTS WITH MALABSORBTION SYNDROMES

DOSE OF 1mg ORAL FOLIC ACID DAILY IS SUFFICIENT TO REVERSE MEGALOBLASTIC ANAEMIA, RESTORE NORMAL SERUM FOLATE LEVELS AND REPLENISH THE FOLATE STORES
THERAPY SHOULD BE CONTINUED TILL UNDERLYING CAUSE OF DEFICIENCY IS REMOVED OR CORRECTED SHOTGUN ANTI ANAEMIA PREPARATIONS

USES :
MEGALOBLASTIC ANAEMIAS DUE TO NUTRITIONAL FOLATE DEFICIENCY, PERNICIOUS ANAEMIA, PREGNANCY, LACTATION, HEMOLYTIC ANAEMIA, MALABSORBTION SYNDROME, PROLONGED ANTIEPILEPTIC THERAPY WITH PHENYTOIN FOLATE ADM WILL REVERSE HEMATOLOGICAL CHANGES OF FOLATE AND VIT B12 DEFICIENCY ANAEMIA, BUT NUEROLOGICAL DEFICIT OF VIT B12 DEF ANAEMIA CANNOT BE REVERSED WITH FOLATE ADM THE USA FDA HAD INTRODUCED GRAINS RICH IN FOLIC RICH SUPPLEMENTATION TO ALL ITS CITIZENS TO REDUCE FOLATE DEFICIENCY. INCIDENCES OF NTDS REDUCED BY 30% BUT THIS WAS FINALLY STOPPED AS IT WAS THOUGHT IT WOULD MASK VIT B12 DEFICIENCY

PROPHYLAXIS : 1mg/day IN PREGNANCY TO REDUCE NTDs

METHOTREXATE TOXICITY : FOLINIC ACID IS USED AS TREATMENT AS IT DOES NOT REQUIRE DHFRase TO CONVERT TO ACTIVE FORM CITROVORUM FACTOR RESCUE

ADVERSE EFFECTS : ORAL FOLIC ACID IS ENTIRELY NON TOXIC, SENSITIVITY REACTIONS MAY OCCUR ON PARENTERAL ADM

ERYTHROPOIETIN

Sialoglycoprotein hormome (MW 34000) produced by peritubular cells of the Kidney.

Anaemia and hypoxia sensed by Kidney cells

Kidney cells

Rapid secretion of EPO

Acts on erythroid marrow

ACTIONS
1. Stimulates proliferation of colony forming cells of the erythroid series. 2. Induces haemoglobin formation and erythroid blast maturation.

3. Releases reticulocytes in circulation

EPO binds to specific receptors that alters phosphorylation of intracellular proteins and activates transcription factors to regulate Gene expression. Erythropoiesis is directly proportion to dose and has no effect on Lifespan of RBC

USES
1. Anaemia of chronic renal failure due to low EPO 25-100 U/Kg s.c. or i.v. 3 times a week (600 U/kg max) Raises Haematocrit and HB Reduces need for transfusion Improves quality of life Start with low dose and titre upwards; Haematocrit between 30-36%, Hb 10-12g/dl 2. Anaemia in AIDs patients treated with zidovudine 3. Cancer chemotherapy induced anaemia 4. Preoperative increased blood production for autologous transfusion during surgery

ADVERSE EFFECTS
EPO is nonimmunogenic

Sudden increase in Haematocrit, blood viscosity and peripheral vascular resistance

Increased clot formation in the A-V shunts Hypertensive episodes Seizures Flu like symptoms lasting 2-4 hrs in some patients

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