Hematological disorders

By : Dr. Sanjeev

Hematological disorders

• Normal hematological levels varies with age and sex

Anemia : - Hb level :

– 6 months to 6 years old : below 11 g /dL– Older children : below 12 g /dL

Severe anemia : below 5 g /dL Moderate anemia : 5 – 10 g /dL

Classification • According to the morphology of red cells or the

etiological factors : MICROCYTIC HYPOCROMIC ANEMIA : 1. IRON DEFICIENCY ANEMIA A. During infancy 1. Nutritional 2. Post – hemorrhagic B . Older children 1. Post – hemorrhagic 2. Nutritional 2. INEFFECTIVE ERYTHROPOIESIS A. Thalassemia B. Pyridoxine responsive anemia C. Dyserythropoietic anemia D. Lead poisoning

NORMOCYTIC NORMOCHROMIC ANEMIA

1. IMPAIRED CELL PRODUCTION ( reticulocyte count low ) A . Leukocytes and platelets normal 1. Physiological anemia of infancy 2. Infections 3. Pure red cell aplasia B . Leukocytes and platelets normal or decreased 1. Chronic renal and liver disease 2. Hypothyroidism C . Leukocytes and platelets reduced 1. Aplastic anemia – hereditary, idiopathic 2. Myeloproliferative disorders – leukemia

2. HEMOLYSIS ( reticulocyte count is high )

MACROCYTIC ANEMIA

1. Megaloblastic erythropoiesis

A. Nutritional

1. Vitamin B12 deficiency

2. Folate deficiency

3. Kwashiorkor

B. Toxic

1. Therapy with antifolate compounds, methotrexate

2. Therapy with anticonvulsant , phenytoin

3. Malabsorption

2. Non – megaloblastic erythropoiesis

A. Chronic hemolytic anemia: folate deficiency

B. Liver disease

C. Hypothyroidism

Approach to a child with anemia Anemia (Hb less than normal level) - No lymph nodes - No hepatosplenomegaly - No petechiae or ecchymosis

----- Nutritional iron deficiency or megaloblastic ----- Pure red cell aplasia ----- Thalassemia trait ----- Lead poisoning ----- Renal disease

Cont..

Anemia (Hb less than normal level) - No lymph nodes - No hepatosplenomegaly - With petechiae and ecchymosis

----- Aplastic anemia ----- Bleeding disorder ----- Coagulation disorder ----- ITP ----- DIC

Cont..

Anemia (Hb less than normal level)

With hepatosplenomegaly ----- Thalassemia

----- Liver disorders

Cont..

Anemia (Hb less than normal level)

With petechiae, lymphadenopathy and hepatosplenomegaly --- Leukamia

--- Infections

--- DIC

Common causes of anemia during neonatal period :

– Hemorrhage : Obstetric accidient, slipped umbilical cord tie, internal hemorrage

– Hemolysis : G – 6 – phosphate dehydrogenate deficiency, pyruvate kinase deficiency, alpha thalassemia, malaria, DIC

– Infections: Intrauterine (viral) or acquired (bacterial)

– Impaired red cell production : Prematurity, small for date

Physiological anemia of early infancy

Hb concentration of cord --- 15 to 18 g/dL

Causes : – 1. Diminished red cell production because of low

erythropoietin levels in early infancy– 2. Increase in the blood volume in a rapidly growing

infants and– 3. A shortened survival of the red cells

Note : - It does not respond to iron or folic acid

therapy. - If Hb level falls below 6 g/dL, a small blood

transfusion is essential to correct it.

Microcytic Hypochromic Anemia Iron deficiency anemiaIron helps to get enough oxygen. Body uses iron to

make hemoglobin. Hemoglobin is a part of red blood cells. Hemoglobin carries oxygen.

less iron ---- less red cell --- less HB --- less oxygen - Most common cause of anemia and usually results from

blood loss. • RBCs tend to be microcytic and hypochromic, and iron

stores are low as shown by low serum ferritin and low serum iron levels with high serum total iron binding capacity.

• Common in rural area and in children from poor socioeconomic status

Iron absorption– Site : - Iron is absorbed in the duodenum and upper

jejunum. – It depends on : Extraluminal and intraluminal factors.– Extraluminal factors : iron absorption is controlled by

the body stores of iron, rate of erythropoiesis and the iron needs of the body.

– Intraluminal factors : iron absorption is regulated by the level of iron in the diet. Ferrous salts are better absorbed than the ferric salts.

– Factors that inhibit : phosphates, calcium, milk and eggs, tannic acid (tea and coffee)

– Factors that enhance : lactose, ascorbic acid, fruit juices and amino acids (cystine, lysineand histidine)

– Hcl of the gastric juice facilitates ---- releasing iron from the ferric complexes (ferrous form)

Mechanism of absorption Absorption occurs in two steps : 1. mucosal uptake and

2. mucosal cells to the plasma

1. mucosal uptake– Apoferritin (mucosal cells protein)– Ferritin (storage form of iron)

Iron + apoferritin = ferritin Ferritin :

– 1. iron delivered to plasma according to its needs. – 2. rest is deposited as ferritin in the mucosal cells

• At the end of the life span of mucosal cells ferritin is sloughed out.

When the iron absorption is :• Enhanced : iron entering directly to the plasma.• Depressed : trapped in the form of ferritin.• Small amount of iron may also be absorbed by the

process of diffusion.

2. Mucosal cells to the plasma– Body iron needs are determined by plasma iron level

or transferrin saturation.– Transferrin (glycoprotein)– Each molecule of tranferrin binds with 2 atoms of iron.

This is called total iron binding capacity (TIBC).

Iron + transferrin– Transferrin in the bone marrow provides iron for the

developing red cells.– If saturation of transferrin is less than 20 % of the total

capacity, iron is made rapidly available for the developing red cells in the bone marrow.

Cellular uptake of iron and transferrin receptors

• Present in : erythroid cells, placental and liver cells, etc.

Iron + transferrin --------- release iron to the cell

• Greatest numbers of transferrin receptors are present in the younger erythroid cells (reticulocytes).

Stores of iron: • Reticuloendothelial cells (as ferritin) and bone

marrow.• Red cells----- breakdown ----- iron liberated ------

taken up by R.E cells and iron is transferred to ferritin for reutilization

• R.E system (principal source)

Sequence of changes in iron deficiency

– Iron stores (liver bone marrow) – diminished– Serum ferritin level – falls – Total iron – binding capacity ( below 15 %) –

decrease– Free erythrocyte porphyrin (FEP) level –

increases– Hemoglobin – decreased – MCV and MCH – decreased– Microcytic hypochromic picture

Causes of iron deficiency

Low iron stores :• If the birth weight of the infant is less (preterm,

small for date)• In twins• If the cord was clamped early (as much as 80 –

100 mL of blood may remain in placenta)• Hemorrhage from cord, placenta• Malnutrition • Parasitic infestation and rapid growth.

Cont.. Reduced iron intake :• Breast milk is better source of

iron.• Cow`s milk ------- poor source• Excessive losses of iron may

occur from the body through apparent or occult bleeding. Common causes :

• Hookworm infestation, Meckel`s diverticulum, Hiatus hernia, Prolapse rectum, Ulcerative colitis, Dysentery and Cephal hematoma

Decreased iron absorptionDecreased iron absorption : • Celiac disease• Calcium salts and rich fibers in the

vegeterian diet

Increased iron demand : • Premature and low birth weight

infants• Rapid growth during infancy and

puberty

Defective iron metabolism :• Sideroblastic anemia• Congenital transferrin deficiency,

Iron is not utilized for erythropoiesis but stored in tissues

Clinical features Symptoms : Fatigue and diminished capability to perform hard labor

------- lack of circulating HB --------- due to depletion of proteins that require iron as a part of their structure.

• Due to deficiency or dysfunction of non – Hb proteins : -• Weakness , pica (eating no edible substance like mud, ice

etc.) , dysphagia , altered resistance to infection, altered behavior.

SIGNS On physical examination :• Pallor Abnormalities of epithelial tissues : • Koilonychia (spoon shaped nails)• Glossitis, angular stomatitis, tongue papillae atrophied• Splenomegaly and cardiac enlargement (systolic and even

diastolic murmur): occurs with severe, persistent, untreated iron deficiency anemia.

Note: There may be no symptoms if anemia is mild.

Laboratory investigations• Hb levels ------ decreased• Hematocrit (packed cell volume or % of RBCs in whole

blood) – decreased• Peripheral blood smear shows : poikilocytosis (variation

in shape) and anisocytosis (variation in size) , microcytic and hypocromic red cells.

• MCV, MCH and MCHC ------ low• Reticulocytes --- decreased• Serum iron level --- less than 30 microgram/dL• Total iron binding capacity (TIBC)--- more than 350

microgram / dL and saturation of transferrin is less than 15 %.

• Serum ferritin level --- decreased• Prussian blue staining of the marrow shows absence of

hemosiderin.

Cont..

Indicator of iron deficiency state : • Serum ferritin ------- less than 10ng /mL

• If iron is less ------- protoporphyrin is not converted into heme --------- free erythrocyte porphyrin level in the blood is increased.

• If ratio between free erythrocyte porphyrin and Hb is above 2.8 microgram / g indicates iron deficiency.

Cont…• hematocrit (Ht or HCT) or packed cell volume (PCV) : - is

the proportion of blood volume that is occupied by red blood

cells

• mean corpuscular volume, or "mean cell volume" (MCV) : - calculated by dividing the hematocrit by the red blood cell count (number of red blood cells per litre)

• mean corpuscular hemoglobin, or "mean cell hemoglobin"

(MCH) : - calculated by dividing the total mass of hemoglobin

by the number of red blood cells in a volume of blood • mean corpuscular hemoglobin concentration, or MCHC : -

calculated by dividing the hemoglobin by the hematocrit

Treatment • Deworming of patients• Change in dietary habits• Wearing of shoes• Causes of persistent blood loss if any (polyps,

ulcerative colitis etc.) need to be treated. Oral iron therapy :• Ferrous sulphate, ferrous fumarate, ferrous

succinate, ferrous carbonate, ferrous lactate, ferrous gluconate.

Dose : 3 – 6 mg /kg of body weight given orally in three divided doses for 6 – 8 weeks. Iron should be continued for another 6 - 12 months to replenish the body's iron stores in the bone marrow.

Cont…

• Vitamin C (improves iron absorption)• Milk (diminished iron absorption) .Iron should not

be given just after the milk – feeds or after food. Causes of failure to oral iron therapy :• Inadequate dosage• Occult bleeding and continuous blood loss• Intolerance to iron• Malabsorption of iron• Wrong diagnosis

Cont….• Patients who cannot tolerate iron by mouth can take it

through a vein (intravenous) or by an injection into the muscle.

Indications :• Intolerance to oral iron• Chronic diarrhea• Bleeding from g.i.t which is aggravated by oral iron

therapy and• Severe bleeding when Hb levels cannot be maintained

with oral iron. Dosage of parenteral iron (iron dextran) : iron (mg) = wt (kg) x Hb deficit (g/dL) x 4 Site : - Deep intramuscular in the upper and outer

quadrant of the buttocks I . V : 250 – 500 mL of saline infused slowly over 6 – 8

hours.

Cont.. Blood transfusion : Indication : • Hb below 4 g / dL• Congestive heart failure• If associated infection prevents proper iron

utilization.

• Packed red cells should be used at a slow rate ( to prevent cardiac overload)

• 1 or 2 doses of frusemide 1 – 2 mg/kg I.V (prevent circulatory overload)