HAEMATINICS

Agents Required in the formation of blood.

ANAEMIA:
Balance between
Production &
Destruction of RBCs
Is DISTURBED
 HAEMATINICS
 a) Blood loss (Acute/Chronic)
b) Impaired RBC formation
1. ↓of essential factors iron , Vit B12 & folic acid
2. Bone marrow depression (hypoplastic
anaemia)
3. Erythropoietin deficiency
c) Increased destruction of RBCS
(haemolysis)
IRON:
Distribution of iron in body:
Total body iron in an adult is 2.5-5gm
> men- 50mg / kg
> women - 38mg / kg
i. Hb – 62%
ii. Iron stores as ferritin & haemosiderin 25%
iii. Myoglobin in muscle 7%
iv. Paranchymal (enzymes) iron 6%
 0.33%

100ml of blood loss = 50mg elemental iron

1g/dl Hb = 200mg of elemental iron
Iron is stored – FERRIC form
Ferric + Apoferritin

Aggregates
Apoferritin + Fe+ ---- Ferritin --------Haemosiderin
not reutilized
 Dietary sources of iron
Rich Liver, egg yolk, oyster, dry
beanes, dry fruit ,wheat
germ, yeast.

Medium Meat, chicken, fish , spinach

banana, apple.

Poor Milk and its product , root

vegetable.
DAILY REQUIREMENT:
Adult male : 0.5 – 1 mg
Adult female : 1-2 mg
Pregnancy : 3-5 mg
Infants : 60 µg/kg
Children : 25 µg/kg
 Diet = 10-20mg iron F
Mucosal Cell PLASMA

HCP 1 Fe

Inorganic Haeme Fe
Fe2+
Fe3+ Fe2+ 35%
Carrier
5%
DMT 1 Protein Fe3+
Feeroportin
Acid reducing agent Ferritin

Iron absorption Iron absorption Transferrin

1. Acid 1.Alkalies +
2.Phosphates TfR
2. Reducing Substances
Engulfed by
Ascorbic acid 3.Phytates
receptr
4.T.C. mediated
Amino acids – SH radical endocytosis
5.Presence of other foods in
3.Meat. the Stomach
Mucosal block
1.Iron - cell →Transported to plasma
2.Or oxidised to ferric form
 complexed with apoferritin →FERRITIN)
Life Span Ferritin 2-4 days (Ferritin curtain)

 Iron dissociates from this complex

 Utilized for Hb synthesis and other purposes
 Tf and TfR are returned to the cell surface to carry
fresh load
 Transport storage & excretion
Iron is stored in RE cells in
Liver,
Spleen
Bone marrow
Hepatocytes & Myocytes as Ferritin and haemosiderin.

Excretion
ADULT MALE:- 0.5-1mg
Exfoliated g.i mucosa, RBC and in bile
Menstruating
Women – monthly loss – 0.5-1mg/day
Pregnacy & Lactation –700mg.
 IRON DEFECEINCY ANAEMIA
IRON:
Abs, UPTAKE, &
DISTRIBUTION Diet Iron Aminoacids
vitc

Haeme Iron NH Iron

<10% absHb >90% Phytates
Phosphates
30% 5%
Tannins
Antacids
Iron abs- ferrous Feabs Trans
Ferritin
form. Max
Iron del 3.5g/d
Fe tissues
Transferrin - Iron
Anaemia
Binding capacty
Hypoxia
Hb – 65%Ferritin 29%
Fe stores Myoglobin 4% En2 2%
Requirement:
Children :25µg/kg
 Infants :60µg/kg
Adult male : 0.5-1mg
Adult female : 1-2mg
Pregnancy : 3-5mg
Causes of iron deficiency anaemia
Microcytic hypochromic anaemia
Malabsorbtion bleeding –(H- pylori)
Hook worm infestation
High risk children
premenopause
 Diagnosis
Specific test plasma ferritin (RIA)
(N: 50 – 150mg /ml)
def < 20mg/ml
 Plasma iron
 transferrin (N: 200-360mg/ml)
def:> 360mg/ml
P/S microcyptic hypochromic
 MCV
ORAL IRON PREPARATIONS:
Best route
Ferrous : Rich source of iron
 Better absorbed
Gastric irritation and constipation : Major adverse
effects
Elemental iron content
Iron Preparations Dosage

Oral Other forms

Ferrous sulfate 20% Ferrous succinate
iron 200mg tab Iron choline citrate
Ferrous gluconate 12% Iron calcium complex 5%
300mg 400mg tab iron
Ferrous Fumarate 33% Ferric ammonium citrate
200mg tab Ferrous aminoate 10%
Colloidal
iron
ferrichydroxide 200mg Ferric glycerophosphate
tab Iron hydroxy polymaltose
Carbonyl iron:
Metallic iron- in powdered form
Decomposition of pentacarbonyl- toxic
compound
Absorbed better and long time in intestine
PK:
200 dmg of elemental iron daily in 3 divided
dose
Taken in empty stomach
 Adverse effects
Epigastric pain,
Heart burn,
Nausea,
Vomiting,
Staining of teeth,
Metallic taste,
Constipation.
Parenteral:

Oral iron is not tolerated

Failure to absorb oral iron
Non compliance of oral iron
Chronic bleeding
Along with erythropoietin in CKD
Iron store can be replenished in a short time
Total Iron = 4.4 body wt kg Hb deficit
g/dl

Iron dextran : iv/im

Ferrous sucrose : iv
Ferric carboxymaltose : iv
Iron isomaltoside-1000 : iv
Iron dextran
High molecular weight colloidal solution
50mg of elemental iron /ml
IM/IV
IM- Absorbed through Lymphatics
Circulate without binding with transferrin
Engulfed by RE cells
IM – 10-30% -locally bound and become unavailable
for utilization for several weeks
25% extra is needs to be added to calculated dose
Not excreted in urine or bile
Antigenic
 IM : Z track technique. Avoid staining
IV after test dose
Total dose – diluted in 500ml of saline – iv
(6-8hrs) –more 8yrs
Adverse effects
Local pain - staining, headache, fever,
arthralgia, fever utricaria, bronchospasm,
chest pain – rarely anaphylaxis. (iv)
IRON CONTENT DOSE ADVERSE USES
PREPARATION EFFECTS

FERROUS Iron 100mg IV Mild reaction Anaemia in

SUCROSE hydroxide + kidney disease
sucrose = RE

FERRIC Ferric 100mg IV in Pain Anaemia

CARBOXYMALT hydroxide + 100ml saline Mild
OSE carbohydrate hypotension
shell Abdominal
pain nausea

IRON Iron + 1-2 g IV over 15 Nausea, CKD,

ISOMALTOSIDE isomaltose min epigastric pain Erythropoietin
abdominal anaemia
cramps,
constipation
Uses :
Iron deficiency anaemia

Megaloblastic anaemia
 Acute iron poisoning
Young children –
 Accidental 10- 20 tab
Gastroenterites,
Bloody diarrhoea
Dehydration
Vomiting ,
Lethargy,
Cyanosis,
Shock,
Metabolic acidosis,
CVS collapse and death.(<6hrs)
℞
TO PREVENT FURTHER
ABSORPTION OF IRON FROM
GUT
Gastric lavage with NaHCo3 to
render iron insoluble.
Egg yolk and milk to complex
iron.
 TO BIND AND REMOVE IRON ALREADY ABSORBED:
 Desferrioxamine 0.5-1gm IM repeated 4-12hrs
 Iv 10-15 mg / kg / hrs max 75mg / kg
 Calcium edetate or DTPA.
 Supportive measures
Fluid and electrolyte balance
Respiration and BP maintained
Diazepam to control convulsion
 ERYTHROPOIETIN
Erythropoietin (EPO) is a sialoglycoprotein
hormone (MW34000)
Produced by peritubular cells of kidney
 Essential for normal erythropoiesis.
 Anaemia and hypoxia sensed by kidney cells

 Rapid screation of EPO

 Erythroid marrow
Stimulates proliferation of colony forming
cells of the erythroid series.

Induces haemoglobin formation and

erythroblast maturation.

Releases reticulocytes in circulation.

Binds to specific receptors (JAK –
STAT)
 alters phosphorylation of
intracellular proteins.
Activates transcription factors
↑ erythropoiesis
 No effect on RBC life span.
EPOETIN:
Alpha and beta
Recombinant human erythropoietin
IV/SC injection
Plasma t ½ 6-10 hrs i.v. or s.c
DARBEPOETIN ALPHA:
 Hyperglycosylated modified preparation
Long acting
Once wkly
USES
Chronic renal failure.Hb <8 g/dl
Anaemia in AIDS – treated with
zidovudine.
Cancer chemotherapy
Preoperative ↑ blood production for
autologous transfusion during surgery.
Adverse effects:
↑ Haematocrit.
Blood viscosity.
Peripheral vascular resistance (PVR)
Flu like symptoms.
 Vitamin B 12
Cyanocobalamin and Hydroxocobalamin –
Complex cobalt compounds in diet.
Vit B12 H2O soluble, thermostable red
crystals.
Dietary sources :
Liver, kidney, sea fish, egg yolk, meat, cheese.
vegetable source – legumes
Commercial source :
streptomytces griseus byproduct of streptomycin
industry.
Daily requirement :
1-3µg, pregnancy and lactation 3-5µg
 Metabolic functions
Folate
Coenzyme of B12
DA B12 (deoxyadenosyl –cobalamin )
Methyl cobalamin.
Essential for the conversion of homocysteine to
methionine

Methyl THFA B12 methionine

THFA methyl B12 homocysteine

Methionine – Methyl donor group- protein synthesis
 THFA – Reutilization
Vit B 12 def : THFA get trapped
One carbon transfer reaction suffer
Purine and pyrimidine synthesis is affected

DAB 12
Malonic acid Succinic acid
DAB12
Methionine S-adenosyl methionine
Methyl-malonic acid- accumulates-
demyelination
For cell growth and multiplication
Utilization of Vit B12
Vitamin B12 + Intrinsic factor

Complex+ receptors on intestinal mucosa

Vit B12 in blood+ beta globulin
transcobalamineII(TCII)
Viit B12 not degraded in the body
Excreted in bile
Enterohepatic circulation
B12 Deficiency
Addisonian pernicious anaemia (an
autoimmune disorder)
Chronic gastritis, gastric carcinoma,
gastrectomy
Malabsorption bowel resection
Consumption of B12 by abnormal flora –
fish tape worm
Nutritional deficiency
↑ demand , pregnancy, infancy.
Manifestations of deficiency
Megaloblastic anaemia
Glossitis
Subacute combined degeneration of spinal
cord . Peripheral neuritis
PREPARATIONS
Cyanocobalamin
Hydroxocobalamin
Methylcobalamin
 USES
Treatment % of B12 deficiency
Prophylaxis
Neuropathies,
psychiatric disorders,
Tobacco amblyopia
Folic acid
Yellow crystals insoluble in water
Chemically pteroyl glutamic acid
pteridine + paraaminobenzoic acid
+ glutamic acid.
Dietary sources :
liver, green leafy vegetables, egg, meat,
(spinach) milk.
Daily requirement :
Adult < 0.1mg.
 Pregnancy, lactation 0.8mg.
Utilzation :
folic acid – polyglutamates
Split off in upper intestine
Reduction to DHFA and methionine
Transported in blood mostly as methyl THFA
Extracted by tissues stored as polyglutamates
Total body store 5-10mg
Metabolic functions
Folic acid is inactive:
FA → DHFA → THFA by coenzyme
Dihydrofolate reductase and folate reductase
1. Conversion of homocysteine to methionine
2. Generation of thymidylate, an essential
constituent of DNA
Deoxyuridylate methylene- THFA glycine

Thymidylate DHFA THFA serine

DHF Rase
3. Conversion of serine to glycine.
4. Purine synthesis.
5. Generation and utilization of ‘formate
pool.’
6. Histidine metabolism → for mediating
form imino group transfer.
7. Ascorbic acid protects folates in the
reduced form.
Deficiency :
Inadequate dietary intake
Malabsorption
Biliary fistula
Chronic alcoholism
↑ demand pregnancy, lactation.
Drug induced → phenytoin prolonged
therapy
 Manifestations
Megaloblastic anaemia
Epithelial damage – glossitis, enteritis,
diarrhoda, steatorrhoea.
General debelity: wt loss, sterility

Preparations of does
Folic acid – oral therapy – 2-5mg / day
Folinic acid
 Uses
Megaloblastic anaemia
1. Nutritional deficiency
2. Increased demand
3. Pernicious anaemia
4. Malabsorption syndrome
Prophylaxis- pregnancy
Methotrexate toxicity
Citrovorum factor rescue
To enhance anticancer efficacy of 5FU
Adverse effects

Non toxic – Oral

Rarely sensitivity reactions – iv