This Pediatric lecture notes on hematology are available for pediatric Speciality nursing students, and Medical Students.

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12. Pediatric Lecture Notes in Hematology1
Contents
12.1. Anemia.
12.1.1. Iron deficiency anemia.
12.1.2. Megaloblastic anemia.
12.1.3. Aplastic anemia.
12.1.4. Hemolytic anemia.
12.1.5. Thalassemia syndrome.
12.1.6. Thalassemia major (Cooley’s anemia).
12.1.7. Sickle cell disease.
12.1.8. G6PD Deficiency.
12.1.9. Hereditary Spherocytosis.
12.2. Bleeding Disorders.
12.2.1. Hemostasis.
12.2.2. Blood coagulation factors.
12.2.3. Approach to Bleeding disorders.
12.2.4. Idiopathic Thrombocytopenic Purpura. (ITP)
12.2.5. Hemophilia.
12.2.6. Von Willebrand Disease.
12.2.7. Disseminated intravascular coagulation (DIC)
12.2.8. Henoch-Schoenlein Purpura (Anaphylactoid purpura)
12.3. Blood and Blood components therapy.
12.4. Transfusion reactions and Management.
12.5. Hematopoietic stem cell transplant.
12.1. Anemia.

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1. Definition:
A. It is defined as Hb concentration in blood bellow the lower
limit of normal or Reduction of RBC volume for age and sex.
OR
B. Reduction in O2 transport capacity of blood as a result of
reduction below normal limit of total circulating red cells.
A. MCV:
Normal: 70 – 80fl.
B. MCH:
Normal: 29.5pgm⁺ 2.5
C. MCHC:
Normal: 32.5%
MCHC is more significant as it is independent of RBC count.
2. Normal Hematological values:
Mean Hb:
a) Cord blood 16.8%.
b) 3 months to 6yrs – 12gm%.
c) 7 – 12 years – 13gm%.
d) Adult: Male – 16gm%, Female – 14gm%.
Hematocrit:
a) Birth – 50-55%.
b) 3month to 6years – 36 – 37%.
c) 7 – 12 years – 38%.
Adult:
a) Female – 42%.
b) Male – 47%.
3. Erythropoiesis:
Pronormoblast
Early normoblast
Intermediate normoblast
Late normoblast.
Reticulocyte Mature RBC
4. Nutritional requirement:
A. Metals: Iron, cobalt, Mn.
PCV/L
RBC Count/L
Hb/L
RBC/L
Hb%
PCV/dL

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B. Vitamins: Vit B12, Folic acid, Vitamin C, Vitamin E Vit B6,
Riboflavin.
C. Amino acids:
D. Hormones: Erythropoietin, Androgens, Thyroxin.
5. Classification:
I. Morphological classification:
a) Microcytic hypochromic Anemia.
b) Normocytic normochromic Anemia.
c) Macrocytic normochromic Anemia.
Causes of Microcytic hypochromic Anemia
a) Iron deficiency Anemia.
b) Thalassemia.
c) Sideroblastic Anemia.
d) Lead poisoning.
II. Pathophysiological classification:
a) Anemia due to Blood loss – Acute blood loss, Chronic
blood loss.
b) Hemolytic Anemia.
c) Anemia due to impaired blood production:
i. Cytoplastic maturation defect.
• Deficient hem synthesis.
• Iron deficiency Anemia.
• Deficient globin synthesis, thalassemia
syndromes.
ii. Nuclear maturation defect – Megaloblastic
Anemia.
iii. Defect in stem cell proliferation
1. Aplastic Anemia.
2. Pure red cell Anemia.
III. Anemia of chronic disease.
1. Bone marrow infiltrations:
a) M. Myeloma.
b) Leukemia.
c) Lymphoma.
d) Myelosclerosis
2. Congenital Anemia:
a) Sideroblastic Anemia.
b) Congenital dyserythropoietic Anemia.
12.1.1. Iron deficiency anemia
1. Introduction:
• Anemia due to lack of sufficient iron for synthesis of hemoglobin
is most commen type of Anemia.
• Body of newborn contains 0.5gm iron while adult contains 5gm.
• Daily requirement – 1mg of elemental iron /kg/day up to
15years.
2. Absorption:

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• In proximal small intestine with the help of duodenal proteins.
• Absorption is 10% to 20%.
• Human milk iron is absorbed 3times more than cow’s milk
absorbed.
3. Etiology: Common 9months to 24 months.
Causes:
• LBW.
• Perinatal hemorrhage.
• Delayed supplementation of cereals beyond 6months.
• Blood loss: Peptic ulcer, Meckel’s diverticulum, polyp,
hemangioma, inflammatory bowel disease, chronic diarrhea, hook
worm infestations and menorrhagia.
4. Clinical features.
• Pallor is most important sign.
• Irritability, Glossitis.
• Pagophagia (Pica) desired to eat unusual such as ice, dirt.
• Koilonychia – spoon shaped nail.
• Hb less than 5gm% - Irritability, Anorexia, tachycardia,
cardiomegaly, hemic murmurs, CHF and tiredness.
• CNS features: Decreased attention span, alertness and learning.
• Increase in Breath holding spells.
5. Laboratory findings: Hb decrease:
• Serum ferritin decreased.
• Serum iron decreased (Normal 50 – 150mcg/dl)
• Serum iron binding capacity is increased.
• PBS, microcytic, hypochromic, anisocytosis, poikilocytosis and
nucleated RBC.
• Red cell distribution (RDW) width is increase.
• Thrombocytosis sometimes.
• Bone marrow hypercellular erythroid hyperplasia.
6. Differential Diagnosis:
• Beta thalassemia trait and other hemoglobinopathies RBC count
increased RDW is raised in iron deficiency anemia.
• Anemia of chronic diseases.
• Lead poisoning – basophilic stippling.
• Sideroblastic Anemia.
7. Treatment:
1. Oral iron therapy – Ferrous salts (20% is absorbed)
Dose – Elemental iron (4-6mg)/kg/day.
Duration – Give for 3months (1month for correction of Hb and 2
months for body store repletion.)
2. Parental iron therapy – Dose in mg = Hb deficit ×weight in kg
×4 (50mg of iron can be given daily I.M.).

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3. Diet – Milk consumption should be reduced to 500ml/day or
less. Iron rich food should be advised like cereals, green leafy
vegetables, jaggery, banana, apple’s, liver, meat, and fish.
4. Blood transfusion in severe Anemia – if Hb is < 4gm packed
cell 2-3 ml/kg.
5. Treat the cause.
6. Deworming.
Response to iron therapy.
• 12 – 24hrs – replacement of intracellular enzyme.
Clinical response – increased appetite, decreased irritability.
• 36-48hours bone marrow change, erythroid – hyperplasia.
• 48 – 72 hours – reticulocytosis peak – 5-7 days.
• 4 – 30 Days increased Hb level.
• 1 – 3 months iron repletion stores.
12.1.2. Megaloblastic anemia.
1. Definition: Megaloblastic Anemia is characterized by:
a) Abnormally large precursor. i.e. Megaloblast.
b) Infective erythropoiesis associated with compensatory
megaloblastic hyperplasia.
c) Prominent Anisocytosis – Macro ovalocytosis, MCV >100mm3
.
d) Abnormal granulopoiesis – leading to Giant metamyelocytes and
hyper segmented neutrophils.
2. Causes:
a) Deficiency of B12.
b) Folate deficiency.
Cow’s and human milk are poor sources of folic acid.
3. Pathogenesis:
a) B12 and folic acid are necessary for DNA formation so
inadequate synthesis of DNA leading to nuclear unmaturation.
b) Synthesis of RNA and proteins is unaffected so cytoplasm
maturation is normal.
c) Both vitamins are necessary for rapidly dividing cells including
myeloid cells and mucosal epithelial cells of GIT.
4. Clinical features:
1) Folate deficiency: Peak age 4-7months.
a) Anemia – irritability, failure to gain weight.
b) May accompany kwashiorkor, marasmus, sprue.
2) B12 deficiency:
a) Peripheral neuropathy – weakness, paresthesias, sensory
deficit, hypotonia, seizures, developmental delay.
b) Subacute combined degeneration of spinal cord in
adults.
c) Angular stomatitis, Glossitis, purpura, anorexia, weight
loss, malabsorption, irritability, tremors and pigmentation
on back of limbs, finger and nose.
5. Laboratory Diagnosis:

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1) Blood test:
a) Hb decreased.
b) PBF – macrocytosis, macroovalocytosis, anisocytosis,
poikilocytosis.
c) Reticulocytes count – normal or decrease.
d) RBC indices – MCV increase, MCH increase, MCHC –
normal or decrease.
e) WBC decrease – Hyper segmented neutrophils.
f) Platelet count normal or decrease.
2) Bone marrow:
a) Cellularity – Hypercellular with decrease M: E ratio.
b) Erythroid hyperplasia with megaloblastic marrow.
3) Biochemical test:
a) Serum B12 Assay.
N200 – 700pg.ml.
<100 significant.
b) Radio Assay.
c) Schilling test.
6. Treatment:
1) Supplementation of folic acid and B12.
Folic acid: Dose: 1-2.5 mg/day for 3-4 weeks.
B12 Dose 5mgm/day.
If neurological involvement then dose is 1mg IM daily for 14days.
2) Blood transfusion if severe Anemia.
3) Role of corticosteroid is controversial.
12.1.3. Aplastic anemia.
1. Definition: It is characterized by failure or suppression of multipotent
myeloid stem cells and resultant pancytopenia i.e. Neutropenia,
Anemia and thrombocytopenia.
2. Etiology:
a) Idiopathic (65%0.
b) Secondary to:
1. Myelotoxic drugs and chemicals like Benzene, alkylating
agents, Antimetabolites (Vincristine, Busulfan)
2. Idiosyncratic reaction caused by chloramphenicol,
chlorpromazine, streptomycin.
3. Irradiation.
4. Infections:
a) Hepatitis virus.
b) AIDS.
c) EB virus.
c) Inherited diseases:
1) Fanconi Anemia.
2) Diamond Blackfan Anemia, pure red cell anemia
(Congenital hypoplastic anemia)
3. Clinical features:

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1) Onset is gradual.
2) Anemia.
3) Infections due to granulocytopenia.
4) Bleeding due to thrombocytopenia.
5) Spleen not enlarged.
4. Lab Diagnosis:
1) Hb decreased.
2) TRBC decrease, WBC decrease, PLT decrease.
3) Bone marrow dry tap or hypocellular marrow or aplastic marrow.
4) Severe Aplastic Anemia:
• Granulocyte count <500/mm3
• Platelet count <20,000/mm3
• Reticulocyte count <1%
• Bone marrow – 25% of hematopoietic cells.
5. Differential Diagnosis:
1) ITP.
2) Leukemia.
3) Myeloid metaplasia.
6. Treatment:
1) Supportive:
d) Blood transfusion.
e) Control of infections with broad spectrum antibiotics. Fungal
infections treated with amphotericin B.
2) Immunotherapy:
a) ALG: Antilymphocyte globin.
b) ATG: Antithymocyte globin.
Dose: 10-15mg/kg/day for 4days.
c) Cyclosporin: 8-10 mg/kg/day orally × 6months.
d) Methyl prednisolone: 10-20 mg/kg/day × 15days.
e) Androgens: 2mg/kg/day for 3-6months.
f) Corticosteroids: 2mg/kg/day × 3-6 weeks.
Taper dose after improvement.
3) Hematopoietic growth factors:
a) G-CSF – Granulocyte colony stimulating factors.
b) Human interleukin 3.
c) Human Erythropoietin.
4) Bone marrow transplantation: Treatment of choice.
12.1.4. Hemolytic anemia.
1. Definition: Hemolytic Anemias are characterized by:
1) Premature destruction of RBC i.e. shortened red cell life span <
120 days (Intravascular hemolysis).
2) Accumulation of products of hemoglobin catabolism.
3) Marked by increased erythropoiesis within the bone marrow.
2. Classification – Two types.
1) Acquired extrinsic hemolytic anemia (Extracorpuscular):
A. Antibody immune hemolytic anemia:

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I. Autoimmune hemolytic anemia:
a) Warm antibody AIHA.
b) Cold antibody AIHA.
II. Drug induced immune hemolytic anemia.
III. Isoimmune hemolytic anemia.
B. Mechanical trauma: Microangiopathic hemolytic anemia.
C. Infections (Direct toxic effect) Malaria, Bacterial
infections.
D. Splenomegaly.
E. Acquired red cell membrane abnormalities, Paroxysmal
Nocturnal Hemoglobinuria (PNH)
2) Hereditary intrinsic hemolytic anemia (Intracorpuscular)
I. RBC cell membrane abnormalities:
1) Hereditary Spherocytosis.
2) Hereditary Elliptocytosis.
II. RBC enzyme defects:
1) G6PD Deficiency.
2) Pyruvate kinase deficiency.
III. Hemoglobin disorders.
1) Hemoglobinopathies.
2) Sickle cell syndrome.
3) Thalassemia.
3. Clinical features:
1) Pallor – Anemia.
2) Positive family history with lifelong anemia.
3) Mild fluctuating Jaundice.
4) Urine turn dark on standing.
5) Splenomegaly.
6) Pigment Gallstones.
4. Laboratory Evaluation:
1) Test suggestive of increased hemolysis:
a) Serum bilirubin – Raised (Indirect).
b) Urine Urobilinogen – raised.
c) Fecal stercobilinogens – raised.
d) Serum haptoglobins – decreased.
e) Serum hemopexins – decreased.
f) Plasma lactic dehydrogenase – increased.
g) Hemoglobinemia.
h) Hemoglobinuria.
i) Methemoglobinemia.
j) Hemosiderinuria.
2) Test suggesting increased Erythropoiesis.
a) Reticulocyte count – increases.
b) PBS – macrocytosis, polychromasia, normoblast, micro
spherocytosis.
3) Bone marrow – Erythroid hyperplasia, raised iron stores.

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4) Special tests:
A. General tests:
i. Osmotic fragility – increased.
ii. Coombs tests positive in acquired hemolytic
anemia.
iii. Hb Electrophoresis.
iv. Test for shortened RBC life span (Chromium
tagged RBC)
B. Specific tests:
i. Fetal Hb estimation.
ii. Sickling tests.
iii. Screening tests for G6PD.
12.1.5. Thalassemia syndrome.
1. Definition: These are heterogenous group of Mendelian disorders
characterized by lack of or decreased synthesis of polypeptide chain
[αglobin chain or ꞵglobin chain or hemoglobin A (α2ꞵ2)]
2. Genetics: ꞵ chains are encoded by two pairs of genes on chromosome 11
and α chains by 2pairs of genes on chromosome 16.
3. Classification: Two types:
A. αThalassemia: There are four αglobin genes. αThalassemia are
classified according no. of genes deleted:
a) Silent carrier state
• Deletion of single αglobin gene.
• Asymptomatic.
b) αThalassemic trait
• Deletion of 2 αglobin gene
c) Hemoglobin H disease.
• Deletion of 3 αglobin gene
d) Hydrops fetalis.
• Deletion of all αglobin genes.
• Not compatible with life.
B. ꞵThalassemia:
Classified according to severity of anemia which is based on type of
genetic defect as well as gene dosage:
1. ꞵ⁰ absence of ꞵchain synthesis of ꞵgene.
2. ꞵ⁺ decrease synthesis of ꞵgene.
C. Homozygous or Heterozygous
a) Thalassemia major Homozygous for ꞵthalassemia gene.
b) Thalassemia minor (trait)
Presence of normal gene (heterozygous)
c) Thalassemia intermedia
i. Genetically heterozygous.
ii. Features between major and minor.
12.1.6. Thalassemia major (Cooley’s anemia).
1. Etiology:

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1) There is complete absence of ꞵchain synthesis ie ꞵ⁰Thalassemia
or only small amount of ꞵchain is formed ie. ꞵ⁺thalassemia
major.
2) Excessive formation of alternate hemoglobin ie. Fetal Hb or
HBA2 (α2 δ2 α2 γ2)
2. Clinical features: Infant born normally.
1) Anemia appears within 4-6 months of life.
2) Hepatosplenomegaly.
3) Thalassemia facies due to expansion of fascial bones because of
erythroid hyperplasia (frontal bossing, prominent maxilla,
malocclusion of teeth, depressed nasal bridge).
4) Features of iron overload
i. Growth retardation.
ii. Delayed puberty.
iii. Diabetes mellitus.
iv. Cardiac failure due to cardiomyopathy, which is due to iron
overload.
3. Laboratory Diagnosis:
1) Hb estimation <5gm%.
2) TRBC decreased, Leukocytosis, Platelet normal.
3) Hematocrit MCV decreased, MCH decrease.
4) Reticulocyte counts increased.
5) PBF – Microcytic, hypochromic anemia, anisocytosis,
poikilocytosis, fragmented RBC, nucleated RBC,
Polychromasia, Basophilic stippling, target cells.
6) Serum Bilirubin increased.
7) Hb electrophoresis – either fetal Hb increased 50to98% or Hb
A2 increase, Hb A1 decrease (0-5%)
8) Osmotic fragility decreased.
9) Serum ferritin raised because of repeated blood transfusions.
10) X-Ray changes.
Hand rectangular appearance of metacarpals.
Skull hair on end appearance.
11) Bone marrow normoblastic erythroid hyperplasia.
4. Thalassemia intermedia:
a) Heterozygous b0
+ꞵ⁺
b) Hb between 5to10gm%
c) Usually anemia detected around 4-5 yrs.
d) Mild Hepatospleenomegaly.
5. Thalassemia minor (Hb 10 – 12 gm)
a) αGene is normal, moderate suppression of ꞵchain (heterozygous).
b) Usually asymptomatic, mild anemia, spleen may be palpable.
c) Free erythrocyte porphyrin is normal.
d) Lab Diagnosis, HbA2 increase slight increase FHb.
6. Management:

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1) Blood transfusions: Repeated blood transfusion to keep the level
of Hb around 9.5 to 10gm%. Every 3-4 weeks, 10-15ml/kg.
Neocyte transfusion younger RBC with longer life span is
preferred.
2) Chelation therapy:
a) Parental therapy with Deferoxamine.
Route: Subcutaneous with pump.
Dose: 25-50mg/kg/day over 8-10hours during night
Days 5-6 nights /week.
Desired ferritin level 1,000 to 2,000mg/ml.
b) Oral chelating agent
Deferiprone
Dose: 75mg/kg/day in 2-3 div. doses.
Side effects: Arthropathy, Agranulocytosis.
c) Newer chelating agents under trial.
3) Bone marrow transplantation: It offers cure.
Indications:
Children younger than 5yrs. Of age without iron overload and
hepatomegaly (should have HLA matched siblings)
4) Splenectomy:
• Indication when rising blood transfusion requirement.
Packed cell requirement above 240ml/kg/ye.
• Preferably age of child should be above 6yrs. To prevent
post splenectomy sepsis.
5) Recent trails: Gene therapy.
6) Vitamin C: 100mg daily.
12.1.7. Sickle cell disease.
1. Definition: It is a type of hemoglobinopathy due to presence of sickle
hemoglobin (Hbs) in RBC. RBC develops sickling when they are
expose to low O2 tension.
2. Cause:
a) Point mutation of globin gene.
b) Substitution of valine for glutamic acid at sixth position of ꞵchain.
3. Type: Three types.
1) Sickle cell trait: Heterozygous state.
2) Sickle cell anemia: Homozygous.
3) Combination:
• Sickle B thalassemia.
• Sickle C disease.
• Sickle D disease.
4. Pathogenesis:
A. Sickling – During deoxygenation RBC containing sickle Hb changes
from biconcave disc to elongated crescent shaped RBC. It is due to
aggregation and polymerization of HbS.
B. Factors causing sickling:
i. Interaction between HbS and other Hb:

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1) Sickle cell trait – In this 40% Hb is HbA. HbA interacts
with HbS weakly so little tendency to sickling.
2) In sickle cell anemia – In this all Hb is HbS so more
sickling.
3) Fetal Hb – doesn’t interact with HbS so newborn do
not manifest vasoocclusive phenomenon.
4) HbC – has greater tendency to aggregate so more severe
disease.
ii. Dehydration: - Higher MCHC during dehydration causes more
sickling.
iii. Anorexia, Acidosis causes sickling.
5. Clinical features:
1) Chronic hemolytic anemia.
2) Chronic hyperbilirubinemia – skin light lemon-yellow color.
3) Gallstones.
4) Splenomegaly, lever enlarged.
5) Non healing leg ulcer due to anemia.
6) Physical growth retardation.
7) Delayed puberty.
8) Clubbing of fingers due to due to chronic anoxia.
9) Cardiomegaly.
10) Vasoocclusive crisis: Results into:
a) Micro infarct in abdomen, chest back, joints, painful
crisis.
b) Micro infarcts in valves, spleen, bones, lungs, kidneys,
liver, skin result in anatomic and functional damage.
c) Auto splenectomy.
d) Acute chest syndrome due to pulmonary infarction with
pneumonitis and fat embolism.
e) Stroke between 6 to 9 yrs of age.
11) Aplastic crisis: Temporary marrow suppression Precipited by
parvo virus and folate deficiency.
12) Infections: increased susceptibility to infection, particularly
salmonella, osteomyelitis, streptococcus pneumoniae, H influenza
infections, due to splenic fibrosis.
13) Acute sickle dactylitis present as ‘hand foot syndrome’
presents during infancy.
14) Acute painful episodes: Most frequent and prominent feature.
15) Priapism.
6. Laboratory Diagnosis:
a) Anemia – Hb decreases moderate to severe.
b) PBF – shows sickle cell and target cells.
c) Sickling tests – positive with reducing substances like sodium
metabisulfate.
d) Hb electrophoresis – HbS positive, HbS 2-20%.
e) Prenatal diagnosis by fetal DNA analysis.

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7. Treatment:
1) Immunization: All infants should be immunized with conjugate
pneumococcal vaccine and other routine vaccines of childhood.
2) Penicillin prophylaxis:
At the age of 2 months
Dose: 2months to 3 years – 125 mg BD and oral > 3years – 125mg
BD oral >3years of age dose – 250mg BD.
3) Folate supplementation:
4) Treatment of pain: Acetaminophen with codeine.
5) Blood transfusion:
Indications:
a) Acute chest syndrome.
b) Stroke, stroke prevention.
c) Severe anemia.
d) Splenic sequestration.
e) Before surgery.
f) Chronic pain syndromes.
6) Treatment of infection: broad spectrum antibiotics.
7) Drug therapy:
Hydroxyurea: MOA 1: Elevates fetal Hb
Dose: 15mg/kg/day gradually increase to 30mg/kg/day.
8) Bone marrow transplantation: only cure in < 16 yrs. of age.
9) Experimental treatments: Aims at increasing intracellular
hydration, decreasing RBC adhesion, lowering blood viscosity,
Elevating N2O level, decreasing thrombosis.
12.1.8. G6PD Deficiency.
1. Introduction:
a) It is X linked trait affecting males while females are carrier
and asymptomatic.
b) In this there is hemolytic crisis Precipitated by:
1) Infections – bacterial, viral.
2) Drugs – Antimalarial, Sulphonamides, nitrofurantoin,
aspirin, Vit k, nalidixic acid.
3) Acidosis
4) Ingestion of fevabeans.
2. Pathogenesis:
Due to deficiency G6PD reduced glutathione is not formed:
a) Hemoglobin is oxidized and denatured by oxidant stress in
G6PD deficient RBC’s.
b) Altered Hb precipitates and forms Heinz Bodies which attach to
RBC membrane and reduces its flexibility.
c) These cells are destroyed by spleen.
3. Clinical features:
a) Hemolytic anemia within hours when exposed to oxidant
stress.
b) It is self-limiting as hemolysis affect old RBC.

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c) Clinical manifestations depend up variant of G6PD deficiency.
i. Type I:
Mild enzyme decreases 8-15% Patients sensitive to strong
oxidants like primaquine and sulfonamide, vitamin k in
large doses.
Hemolysis only initially.
ii. Type II:
a) Hemolysis continues on continuous administration
of drugs.
b) Hemolysis with viral hepatitis.
c) Neonatal hyperbilirubinemia is common.
iii. Type III:
a. Hemolytic anemia without exposure to drugs.
b. Jaundice in newborn.
c. Severe hemolysis on drugs.
d. Febrile illness may precipitate hemolysis.
4. Diagnosis:
a) RBC shows Heinz bodies.
b) Assay of G6PD.
5. Treatment:
a) Avoid oxidant stress.
b) Sodium bicarbonate to alkalinize urine.
c) Blood transfusion if severe anemia.
12.1.9. Hereditary Spherocytosis.
1. Definition: It is hereditary hemolytic anemia in which red cell
membrane is abnormal.
2. Pathogenesis: Deficiency in structural protein of RBC membrane
spectrin.
3. Inheritance: Autosomal dominant.
4. Clinical features:
a) Anemia.
b) Splenomegaly.
c) Jaundice.
d) Pigment Gallstone.
5. Lab Diagnosis:
a) Hb decrease mild to moderate.
b) Reticulocyte count increase – 5-20%.
c) PBS – microspherocytes.
d) Osmotic fragility is increased.
6. Treatment:
1) Splenectomy after 5 yrs. of age.
2) Partial splenectomy in younger than 5 years of age.
3) Folic acid supplementation (1mg daily)
4) Post splenectomy prophylaxis.
a) Vaccines for pneumococcus, H. influenza, meningococcus.
b) Oral Penicillin V (125 – 250mg. BD)

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12.2. Bleeding Disorders.
12.2.1. Hemostasis.
1. Definition: Spontaneous arrest of bleeding by various physiological
process after the injury is known as hemostasis.
2. Mechanism: It includes three stages:
• Stage I:
Vascular response: Vasoconstriction of blood vessels by vWF,
Endothelin and thrombo axane A2.
• Stage II:
Formation of temporary Hemostatic plug by platelets as
follows:
1) Platelet adhesion and activation.
2) Platelet aggregation.
3) Platelet plug formation.
• Stage III: Clot formation by coagulation factors.
12.2.2. Blood coagulation factors.
1. Factors:
I. Fibrinogen.
II. Prothrombin.
III. Tissue thromboplastin.
IV. Calcium.
V. Labile factor or pro-accelerin.
VI. Activated labile factor.
VII. Stable factor/Proconvertin F.
VIII. Antihemophilic factor.
IX. Christmas factor (PTC)
X. Stuart power factor.
XI. Plasma thromboplastin Antecedent (PTA)
XII. Hagman factor.
XIII. Fibrin stabilizing factor.
2. Coagulation Disorders:
• Hereditary Disorders:
1) Hemophilia A – Factor VIII deficiency.
2) Hemophilia B – Factor IX deficiency.
3) Hemophilia C – Factor XI deficiency.
4) Para Hemophilia – Factor V deficiency.
5) Other factor deficiencies VII, X, XII, XIII.
6) Von Willebrand’s disease – vWF deficiency.
• Acquired disorders:
1) Vitamin K deficiency – decrease level of factor II, VII, IX,
X.
2) Hemorrhagic disease of newborn (HDN) vitamin K
dependent factor deficiency.
3) Liver diseases.

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4) DIC.
12.2.3. Coagulation Cascade:
Intrinsic pathway factor XII Xlla Extrinsic pathway injury
XI XIa Tissue factor
IX IXa Activates FVII
Factor VIII Calcium phospholipid
Complex Activates FX
Factor X Xa
Factor Xa + FactorV + Calcium Phospholipid
Thromboplastin
PHASE II:
Prothrombin factor II Thrombin
Fibrinogen Fibrin
Factor XIII
Stable Clot
1. Phase I: Disorders assessed by APTT. Diseases – Hemophilia.
2. Phase II: Assessed by prothrombin time caused by liver diseases.
3. Phase III: Assessed by thrombin time, Diseases – Afibrinogenemia,
Dysfibrinogenemia.
12.2.4. Approach to Bleeding disorders.
1. History: Helps in provisional diagnosis.
a) Age:
i. Coagulation factor deficit early in life.

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Example:
1) Umbilical cord bleeding point towards hemophilias
or coagulation factor deficiencies.
2) Intramuscular injection causes hematoma formation
points towards coagulation disorders.
3) Circumcision causing excessive bleeding point
toward coagulation disorders.
ii. Purpura: manifest later in life
b) Sex: Hemophilia A & B are seen in males while von Willebrand
disease seen in females.
c) Family history: of bleeding disorder usually points towards
plasma coagulation disorders.
d) Menstrual history: Menorrhagia usually points towards von-
Willebrand’s disease.
e) Severity of Bleeding:
1) Development of petechiae or small multiple ecchymosis
spontaneously points towards plasma coagulation disorders
like purpuras.
2) Deep bleeding in joints (Hemarthrosis) and muscle or
diffuse spreading ecchymosis and hematoma suggest
Hemophilias.
2. Clinical Examination:
• Petechiae:
1to2 mm hemorrhages into skin, mucous membrane and serosal
surface is called petechiae. It is seen in platelet disorders and
vasculitis.
• Purpura:
Small hemorrhages in skin or mucous membrane more than 2mm
are called purpura. They are seen thrombocytopenia’s and
vasculitis.
• Ecchymosis:
Subcutaneous hematomas of more than 1cm are called
ecchymosis.
Small and multiple ecchymosis can be seen in purpura but big
spreading ecchymosis are seen in coagulation disorders.
• Hematomas:
Collection of blood under skin or in muscle of more than 1cm
are called hematomas. They are usually seen in coagulation
disorders.
• Hemarthrosis:
Collection of blood in joint is seen in hemothrosis philias.
3. Always rule out the possibility of systemic diseases causing bleeding
diathesis like leukemia, DIC, pancytopenia, meningococcal meningitis,
hemorrhagic fever.
4. Laboratory tests:
A. First line test:

18. Dipti’s Page 18 of 31
i. BT (4-8 min)
ii. CT (3-6 min)
iii. Platelet count (N=1.5lacs to 4.0lacs)
iv. CBS to rule out pancytopenias.
v. PBS to rule out leukemias.
Prolonged BT:
1) Increase BT with low platelet count suggest-
2) Increase BT with normal platelet count suggest:
Henoch – Schoenlein purpura.
Prolonged CT suggest:
i. Coagulation factor deficiency.
ii. Von Willebrand disease.
iii. Vitamin K deficiency.
iv. Liver disease.
v. DIC.
B. Second line test:
i. APTT (Activated partial thromboplastin, normal 60 –
85sec)
ii. TT (Thrombin time, normal 11 – 15sec)
iii. PT (Prothrombin time normal 10 – 13sec)
Only PT prolonged
Factor VII deficiency.
Only APTT prolonged (Coagulation disorders)
i. Hemophilia A, B, C.
ii. von Willebrand disease.
iii. F XII deficiency.
Both PT and APTT prolonged
i. Vitamin K deficiency.
ii. Liver diseases.
iii. DIC.
iv. Congenital deficiency of V, X, XII.
C. Third line test:
i. Mixing studies: Add normal plasma to plasm of patient. If
it corrects APTT it suggests deficiency of F VIII, IX, XI
i.e. Hemophilias.
ii. Specific factor assays: VIII, IX, XI.
a) It helps in diagnosis of hemophilia A, B, C.
b) vonWillebrand factor assay.
D. Fourth line Assay:
i. Reptilase time: It uses snake venom to clot fibrinogen. It is
increased in hypofibrinogenemia but not with heparin.
ii. Platelet aggregation test: It is indicated when qualitative
platelet function defect is suspected.
iii. E.L.T. (Euglobin clot lysis time): Test to evaluate
fibrinolytic system.
12.2.5. Idiopathic Thrombocytopenic Purpura. (ITP)

19. Dipti’s Page 19 of 31
1. Definition: It is an immune thrombocytopenic purpura.
2. Types: Two types.
1) Acute – Commonly seen in children.
2) Chronic – Commonly seen in adults.
3. Etiology: Acute ITP
It follows, 1to4 weeks after viral infection. It is caused by autoantibody
that binds to platelet membrane. These antibody – coated platelets
are destroyed in spleen by macrophages.
Combines with Fc portion of macrophages in spleen, ingested
and destroyed in and ultimately leading to thrombocytopenia.
4. Clinical features:
1) Age 1-4 years, history of preceding viral infections 1to4weeks
before the onset of purpura.
2) Sudden appearance of generalized petechiae and purpura.
3) Bleeding from gums and mucous membranes.
4) Splenomegaly is rare.
5) Hepatosplenomegaly and lymphadenopathy suggest other
diagnosis.
6) <1% cases develop increased hemorrhage.
7) Spontaneous resolution occurs within 6months in majority of
cases (70-80%)
5. Laboratory Diagnosis:
1) Platelet count decreased severe thrombocytopenia is common.
2) Bone marrow to rule out other causes like aplastic anemia and
leukemia.
3) Antinuclear antibodies (ANA) positive in adolescent.
6. Treatment:
1) IVIG (intravenous immunoglobulin)
Dose – 0.8 to 1gm /day for 1to2 days.
2) Prednisolone: Induces rapid rise in platelets.
Dose: 1to4mg/kg/day.
Duration – 2to3 weeks till platelet count is above 20,000/mm3
3) I.V. anti D therapy: Given to Rh positive individuals.
Dose 50mg/kg/2days.
MOA – combines with macrophage Fc receptors so interferes
with platelet destruction.
4) Splenectomy.
Indications:
a) Severe ITP more than 1year (chronic ITP in a child of >
4yrs age.)
b) Symptoms are not easily controlled with above therapies.
7. Chronic ITP: (10-20% cases)
1) Definition: Persistent thrombocytopenia for more than
6months
2) More common in females and adults in 20-40years of age.
3) A preceding viral infection is not seen.

20. Dipti’s Page 20 of 31
4) Splenectomy is successful in 64-88% of children.
12.2.6. Hemophilia.
1. Definition: Congenital coagulation factor deficiency bleeding
disorders.
2. Three types:
1) Hemophilia A – Factor VIII deficiency.
Inheritance – X linked recessive.
2) Hemophilia B – Factor IX deficiency.
(Christmas disease)
Inheritance – X linked recessive.
3) Hemophilia C – Factor XI deficiency
Autosomal recessive.
3. Hemophilia A and B.
Most common severe inherited bleeding disorder seen in males.
4. Pathophysiology:
1) Factor VIII and Factor IX activates Factor X which generates
thrombin further it is activated fibrinogen to fibrin.
2) Deficiency causes delayed formation of clot and is not strong so
hemophilia patient does not bleed more rapidly.
5. Clinical features:
1) Affects male only.
2) Factors do not cross placenta so; bleeding symptoms may be
from birth.
3) Neonates may have intracranial hemorrhage.
4) Infant can bleed with circumcision.
5) There may be easy bruising when infant begins to crawl and walk.
6) Intramuscular hematomas are seen.
7) Hemarthrosis is hallmark of hemophilia.
Appears mostly commonly in ankles, knee and elbow.
8) Recurrent bleeding in joints may become spontaneous.
9) Life threatening bleeding can occur in vital structures like CNS,
upper airways, GIT, iliopsoas muscles.
10) Prolonged bleeding after minor surgery like dental extraction or
tonsillectomy can be there.
6. Grading of Severity:
1) Severe Hemophilia <1% of clotting factor.
2) Moderate Hemophilia 1-5% clotting factor.
3) Mild hemophilia >5% to 30%.
7. Genetics:
1) Hemophilia A & B are X linked traits.
2) Males are suffering, females are carrier.
3) Factor VIII is carried in plasma by vWF factor so Ratio of factor
VIII to vWF helps to diagnose carriers of hemophilia.
8. Laboratory Diagnosis:
1) APTT is increased.

21. Dipti’s Page 21 of 31
2) Normal – Platelet count, Bleeding time, Prothrombin time and
thrombin time.
3) Mixing studies – mixing of normal plasma with patient’s plasma
results in correction of APTT.
4) Assay of factor VII & IX.
5) Quantitative Bethesda Assay – This test helps in detection of
inhibitors (antibodies) against active clotting site.
9. Treatment:
I. Replacement therapy:
When bleeding occurs levels of factor VIII or IX must be raised
and hemostatic level i.e. 35 – 40 units/dL.
For life threatening or major hemorrhage to 100U/dL.
Factors are replaced to stop bleeding in following three ways:
A. Fresh frozen plasma:
a) One unit contain 200 units of factor VIII/IX.
b) Risk of blood transmitted infections like Hepatitis B, C,
HIV, CMV.
c) One unit of factor VIII raises factor VIII by 2% while
one unit of factor IX raises factor raises factor IX by
1%.
d) Half life of factor VIII 18 – 12 hours.
B. Cryoprecipitate (CPT):
1) Prepared from single unit of plasma and contains
factor VIII, von Willebrand factor and fibrinogen.
2) Single bag contains 100units of factor VIII
activity and 0.25 – 0.3gm of fibrinogen in 10ml.
3) Advantages – can be given in small volume.
4) Disadvantages:
a) Requires shortage in deep freeze.
b) Difficult to reconstitute and administer.
c) Factor VIII content is variable.
d) Cannot be subjected to viral attention.
C. Factor VIII concentrate: It is of two types:
1) Plasma derived F VIII concentrate:
• Viral safety is not 100%.
• Risk of human parvovirus B19 virus.
• Advantage:
 Easy to store, reconstitute and infuse.
 Can be carried by patient while travelling.
• Disadvantages – Expensive.
2) Recombinant F VIII contrate: Is safest.
Dose in units VIII – units/dL – Desired rise in plasma ×
Body weight in kg × 0.5.
Dose of factor IX – Desired rise in plasma × Body weight
in kg × 1.4
D. Factor IX concentrate:

22. Dipti’s Page 22 of 31
a) Prothrombin complex concentrate:
i. Contains all vitamin k dependent factors (II,
VII, IX, X, protein C and S).
ii. Advantage – Cheap.
iii. Disadvantages
 Risk of viral transmission.
 Thromboembolic complications.
iv. Indications
 Hemophilia B.
 Hemophilia A & B with inhibitors.
b) Purified factor IX concentrates safest
1) Hemarthrosis Treatment:
Hemophilia A: 20 – 40 units/kg of factor VIII concentrate
repeat the dose daily till joint function is normal.
Hemophilia B: 40 units/kg of factor IX. Repeat the dose
daily till joint function is normal.
2) Muscle Hematoma or subcutaneous hematoma:
Hemophilia A 20units/kg.
Hemophilia B 40units/kg.
Repeat on alternate days till normal.
3) Epistaxis:
1. Apply pressure for 20minutes.
2. Pack with petroleum gauze.
3. Antifibrinolytic therapy – if no improvement then gives
factor VIII 20units/kg for hemophilia A. In case of
hemophilia B give 30units/kg. if
4) Major surgery:
Hemophilia A: 50 – 75 units/kg of factor VIII then
continuous infusion of 2 – 4unit /kg/hr for 24 hrs then 2 – 3
units/kg/hr × 7days.
Hemophilia B: 120units/kg. every 12 – 24 hours.
5) Hematuria:
• Hemophilia A:
1. Bed rest.
2. Maintenance fluids - 1½ times wait for 1-2days if not
controlled then give.
3. Factor VIII 20units/kg. if not controlled give –
Prednisolone.
• Hemophilia B: Factor IX given 40units/kg.
Prophylaxis: It is lifelong.
1. Prevention of trauma.
2. Avoid Aspirin and NSAIDs.
3. Immunize against Hepatitis B.
4. Hemophilic A: 20units/kg of factor VIII/EOD.
Hemophilic B: 30 units/kg of factor IX every 2-3days.
Chronic complications:

23. Dipti’s Page 23 of 31
1) Joint destruction.
2) Transfusion acquired infectious diseases.
3) Development of inhibitors against factors.
II. Drug therapy:
A. EACA: (Epsilon Aminocaproic Acid)
B. Tranexamic acid:
MOA: They prevent lysis of clot.
Indications: Oral bleeds.
Dose: EACA - 75mg/kg/Dose × 6hourly orally for 7-
10days.
C. Estrogen preparation:
It raises factor VII, VIII, IX, X and vWF in normal persons
and in mild deficiency disorders.
D. Desmopressin or DDAVP:
Treatment of mild to moderate hemophilia A only.
MOA: It increases factor by releasing from stores.
Dose: 0.3mg/kg.
Routes: I.V./SC/intranasally diluted in 50ml / saline I.V..
Intranasal Dose: 150mgm (1puff) for children weighing
<50kg and 300mgm (2puff) for weight >50kg.
E. DANAZOL: It increases factor VIII & IX.
F. Fibrin Glue: It seals bleeding sites.
Home infusions: Patient and parents should be trained for
home therapy.
III. Gene therapy: Prophylaxis.
Hemophilia C:
a) Caused by factor XI deficiency.
b) Inheritance – Incomplete autosomal recessive disease.
c) It affects Both male and females.
d) Spontaneous bleeding is rare.
e) Homozygous can have spontaneous bleeding
4. Antenatal Diagnosis:
1) Factor VIII c Assay by radioimmunoassay in fetal blood at 18-
20 weeks of gestation in male fetuses.
2) DNA probe by utilizing Amniotic fluid fibroblasts.
3) Chorionic villus sampling for molecular biologic technique.
4) PCR.
5) Oligonucleotide primers.
12.2.7. Von Willebrand Disease.
1. Definition: Inherited bleeding disorder caused by deficiency of vW
factor.
• More common than hemophilia A.
• Transmitted as autosomal dominant. Chromosome 12 contains the
gene for vWF.

24. Dipti’s Page 24 of 31
• Transmitted as autosomal dominant disorder in in most cases but
autosomal recessive disorders have been identified.
2. Etiology: Three types.
i. Type I – vWF Quantity reduced.
ii. Type – II Quantitatively abnormal.
iii. Type – III vWF absent.
A. Reduced quantity or absent circulating vWF:
Type I and Type III
Type I Autosomal dominant mild 70% cases.
Type III:
i. Autosomal recessive – severe type.
ii. Extremely low level of vWF less common.
iii. Associated with gene deletion and frame shift mutation.
B. Qualitative defects of vWF:
1. Type II – 25% cases.
2. Subtypes several – Type II A is most common.
3. Inherited as autosomal dominant disorder.
4. Associated with missense mutation.
5. Functions of vWF:
1) It helps in addition of platelets to subendothelial collagen via
glycoprotein GP – I Ib IX platelet receptor.
2) Carrier for factor VIII
Source: vWF is produced by:
a) Endothelial cells – major source.
b) Megakaryocytes.
c) Platelet α granules.
6. Clinical features:
a) Spontaneous bleeding – From mucous membrane. – Epistaxis,
gingival bleeding.
b) Excessive bleeding from wounds.
c) Menorrhea.
d) Bleeding into joints – uncommon.
e) Bleeding with procedures.
f) Bleeding may diminish during pregnancy because factors level
increase during pregnancy.
7. Lab diagnosis:
a) BT prolonged.
b) Platelet count – normal.
c) Prolonged bleeding time in presence of normal platelet count.
d) PTT is prolonged. – Secondary decrease in factor VIII level
causes prolongation of PTT.
e) Plasma level of vWF is reduced. It is measured by restocetin co-
factor activity.
f) Von Willebrand antigen assay immunologically.
g) Plasma factor activity.
h) vWF structure.

25. Dipti’s Page 25 of 31
8. Treatment:
a) DDAVP is treatment of choice for mild to moderate deficiency.
Good response only in type I.
b) For severe deficiency.
• vWF concentrate (Humate P) – 1 unit /kg will increase
plasma level by 1.5 unit%.
• Concurrent therapy uses plasma derived vWF containing
both vWF and factor VIII.
c) Avoid aspirin.
d) Hepatitis B vaccine.
e) Antifibrinolytic agent – Epsilon Amino caproic acid (EACA)
f) Platelet transfusion in type – PT vWD (Pseudo vWD) and BSS
(Bernard Saular syndrome)
12.2.8. Disseminated intravascular coagulation (DIC)
1. Definition: It is a syndrome characterized by:
a) Activation of coagulation sequence in vessels that leads to
formation of microthrombi in microcirculation.
b) Increased consumption of platelets and plasma clotting factors.
c) Resulting in prolonged bleeding at multiple sites by activation of
fibrinolytic mechanism.
2. Etiopathogenesis:
a) It is not a primary disease – Coagulopathy occurs with variety of
diseases.
b) Two major mechanisms trigger DIC:
1) Release of tissue factor or thromboplastic substances into
the circulation.
2) Widespread injury to endothelial cells. It causes release
of tissue factor promoting platelet aggregations and
activating intrinsic coagulation.
c) Thromboplastin substances may be derived from variety of
sources like placenta, granules of leukemia, massive tissue
destruction, sepsis.
d) DIC ultimately results in:
1) Thromboembolic phenomenon causing tissue ischemia
and necrosis.
2) Consumption of clotting factors and platelets leading to
bleeding.
3) RBC fragmentation – microangiopathic hemolytic
anemia.
4) Finally shock and death.
3. Causes of DIC:
1) Bacterial septic shock.
2) Viral – Varicella, measles, Hepatitis.
3) Fungal – Candida.
4) Others – Malaria.

26. Dipti’s Page 26 of 31
5) Tissue injury – crush injury, fractures, Burn, Hypo and
Hyperthermia.
6) Malignancies – Acute leukemia, Neuroblastoma.
7) Venoms or toxins – snake bite, insect bite.
8) Hematological – Incompatible blood transfusion, sickle cell
anemia, iron toxicity.
9) Neonatal – Septicemia, Birth asphyxia, RDS, Rh incompatibility,
Necrotizing enterocolitis.
10) Miscellaneous – Vasculitis, purpura, fulminans, heat stroke,
diabetic acidosis, Giant hemangioma, acute pancreatitis.
4. Clinical features:
1) Bleeding – Purpura, echymotic patches, bleeding from mucous
membrane and easy bruising gums.
2) Features of shock.
3) Thromboembolic phenomenon hematuria, oliguria, acute renal
failure.
4) GIT – Abdominal pain, ileus, vomiting.
5) Respiratory – Respiratory distress, cyanosis.
6) CNS – convulsions, coma.
5. Laboratory Diagnosis:
1) Low platelet count.
2) Prolonged PT, APTT, TT time.
3) Fibrin spilt products increase.
4) PBS – RBC fragmentation.
6. Treatment:
1) Treatment of underlying cause.
2) Treatment of Aggravating factors like:
a) Acidosis – Sodium bicarbonate.
b) Hypoxia – O2.
c) Shock – I.V. fluids, dopamine.
d) Electrolyte Imbalance.
3) Anemia – Packed cells.
4) Vitamin K.
5) Hydrocortisone – for purpura fulminans and meningococcemia,
dose: 50 to 100mh/kg 6-8 hrly × 3days.
6) Blood transfusion – fresh.
7) Platelet infusion thrombocytopenia.
8) Cryoprecipitate for hypofibrinogenemia.
9) Fresh frozen plasma for coagulation factors.
10) Exchange transfusion.
11) Anticoagulant therapy.
Indications – when replacement therapy with factors is ineffective.
Drug of choice – Heparin.
Dose – 100units/kg as bolus followed by 20 units/kg/hr.
Maintain – APTT at 1.5 times normal.
12.2.9. Henoch-Schoenlein Purpura (Anaphylactoid purpura)

27. Dipti’s Page 27 of 31
1. Definition: It is non thrombocytopenic purpura due to vasculitis of
small blood vessels.
2. Etiology:
a) Unknown.
b) Follow URI.
c) Age: 2 – 8 yrs.
d) Sex: M: F – 2:1
e) Season – Winter.
3. Pathogenesis:
A. IgA mediated vasculitis of small blood vessel.
B. Deposition of IgA and C3 in small blood vessels of skin and
renal Glomeruli and GIT.
4. Clinical features: Onset – Acute or insidious.
1) Fever, Fatigue.
2) Typical Rash – Hallmark.
Start as pinkish maculopapular rash progress to petechiae or
purpura.
Purpura are palpable and evolve from red to purple or rusty
brown before they fade.
Lesions occur in crops and lasts 3-10days. May appear at intervals
which vary from few days to 1year. Bellow waist over buttock,
back, eyelids, lips, scrotum, dorsum of hands and feet’s.
Angioedema may precede purpura occurs on dependent parts.
3) Arthritis – 60-70% cases, site knee, ankle with edema. Resolve
without deformity.
4) GIT:
a) Intermittent abdominal pain – colicky.
b) Occult heme positive stool.
c) Diarrhea with or without blood.
d) Hematemesis.
e) Intussusception may occur.
5) Renal involvement: 25-50% cases.
Glomerulonephritis, asymptomatic hematuria, renal failure.
6) Hepatosplenomegaly.
7) Lymphadenopathy.
8) CNS involvement – Rarely seizures, paresis and coma.
9) Rare complications:
a) Rheumatic like nodules.
b) Cardiac involvement.
c) Mononeuropathy.
d) Pancreatitis.
e) Pulmonary and intramuscular hemorrhages.
5. Diagnosis:
1) Clinical Features: Palpable purpuric lesions on lower trunk and
thigh.
2) Laboratory Findings:

28. Dipti’s Page 28 of 31
i. Moderate thrombocytosis.
ii. Moderate leukocytosis.
iii. ESR increase.
iv. Anemia.
v. IgA increase, IgM increase.
vi. Urine exam – RBC, WBC casts, Albumin.
vii. Biopsy of cutaneous lesions: Leuko-clastic angitis.
viii. Renal biopsy: Show IgA mesangial and occasionally IgM,
C3, Fibrin deposition.
6. Treatment:
1) Adequate hydration.
2) Bland diet.
3) Pain control with acetaminophen.
4) Rest during acute phase.
5) Complications managed by giving corticosteroids I.V.
Dose: 1-2mg/kg in 24hrs. shows dramatic improvement
6) Rheumatoid nodules: Colchicine 0.6mg/24hrs, alternate day.
7) Hypercoagulable state – Baby aspirin (75mg).
7. Complications:
1) Renal involvement.
2) Bowl perforation.
3) Testicular torsion.
8. Progress:
Self – limited disease with excellent prognosis. < 1% develops renal
failure.
12.3. Blood and Blood components therapy.
Indications of Blood Transfusions:
i. Blood loss.
ii. Shock (loss of >25% of blood volume)
iii. Decrease Hemoglobin.
• Newborn Hb <12gm%.
• 1-4month Hb <10gm%.
a) Perioperative period.
b) Marrow failure.
c) Symptomatic chronic anemia.
iv. Thalassemia.
v. Neonatal sepsis.
vi. Exchange transfusion (See in following table)
S. No. Blood component therapy
1 RBC a) Decrease O2 carrying capacity.
b) Anemia.
2 Platelet transfusions a) Severe thrombocytopenia platelets
<50,000/L.
b) Platelet functions defects.
c) Bone marrow failure.

29. Dipti’s Page 29 of 31
3 Granulocyte transfusions. a) When absolute neutrophil count is
<500cells/mm3
along with fulminant
infections.
b) Septicemia.
4 Fresh frozen plasma a) Multiple clotting factor deficiency.
b) DIC.
c) Thrombotic thrombocytopenic purpura.
d) Anticoagulant protein III, protein C,
protein S deficiency.
5 Cryoprecipitate a) Hypofibrinogenemia.
b) Factor XIII deficiency.
6 Recombinant factor concentrates Hemophilic bleeding
7 Albumin Nephrotic syndrome
8 Immunoglobulins
12.4. Transfusion reactions and Management.
1. Major hemolytic reactions (Incompatibility)
Features: Acute shock, Back pain, flushing, early fever, intravascular hemolysis,
hemoglobinemia.
Management:
a) Stop transfusion.
b) Hydrate by I.V. fluid.
c) Support B.P.
d) Maintain high urine flow.
e) Alkalinize urine.
f) Check for hemoglobinuria, hyperkalemia, jaundice and anemia.
2. Febrile reaction:
Features:
a) Fever at end of transfusion.
b) Urticaria.
c) Chills.
Treatment:
a) Pretreatment with hydrocortisone, antipyretic, diphenhydramine.
b) Use leukocyte poor RBC, washed RBC, filtered frozen RBC’s.
c) Filtration of blood to remove WBC.
3. Allergic reactions:
Features:
a) Fever.
b) Urticaria.
c) Anaphylactoid reactions.
Treatment:
a) Diphenhydramine, hydrocortisone.
b) Use washed RBC.
4. Graft VS host diseases.
5. Blood borne diseases.
a) HIV.
b) Malaria.

30. Dipti’s Page 30 of 31
c) Syphilis.
d) Brucellosis.
e) Hepatitis B, C.
f) Cytomegalovirus.
g) G.B. virus.
h) Parvovirus.
i) Chagas disease.
6. Fluid overload.
7. Iron overload.
8. Electrolyte and acid imbalance.
12.5. Hematopoietic stem cell transplant.
1. Stem cells:
They are unspecialized cells, which are capable of dividing and renewing
themselves for long period and can give rise to specialized cells type regardless of
their source.
2. Types of stem cells:
1) Adult stem cell – found in tissues or organ.
2) Embryonic stem cell.
3. Types of transplant:
1) Autologous transplant: Patient receive their own stem cells.
2) Synergic transplant: Patient receive stem cells from their identical twins.
3) Allogenic transplant: Patient receive stem cell from someone other than
patient or identified twin.
4. Sources of Hematopoietic stem cells.
1) Bone marrow stem cells (BMT).
2) Peripheral blood stem cells (PBSC).
3) Umbilical cord stem cells.
5. Procedure:
1) Harvesting: Procedure for obtaining bone marrow (Pelvis or sternum).
2) Processing: Removal of blood and bone fragments from bone marrow.
3) Cryopreservation till needed. They are freezed and mixed with
preservatives.
4) Transplantation:
a) First marrow of patient is destroyed by chemoradiation.
b) Immunosuppression by methotrexate, cyclosporin, tacrolimus,
corticosteroids.
c) Patient receives stem cells intravenously.
d) Engraftment – After entering blood stream stem cells reach bone
marrow and produces new cells within 2to4 weeks.
5) Recovery of immune functions takes from months to 1to2 years.
6. Clinical indications
1) Acquired diseases:
a) Aplastic anemia.
b) Acute myelogenous leukemia (AML)
c) Acute lymphoblastic leukemia (ALL).

31. Dipti’s Page 31 of 31
d) Myeloproliferative disorders:
 Refractory anemia.
 Chronic myelomonocytic leukemia.
e) Lymphomas – Relapsing.
f) Neuroblastoma.
g) Brain tumors – Resistant to conventional therapy.
h) Solid tumors:
 Alveolar rhabdomyosarcoma.
 Anaplastic Wil’s tumor.
 Skeletal osteogenic sarcoma.
2) Genetic diseases:
a) Immunodeficiency disorder.
b) Fanconi anemia.
c) Storage diseases.
 Adreno leukodystrophy.
 Metachromatic leukodystrophy.
 Hurler syndrome
d) Thalassemia.
e) Sickle cell disease.
f) Other congenital anemias – Diamond Blackfan syndrome
(Congenital pure red cell anemia).
7. Post-transplant side effects:
a) Short term side effects: Nausea, vomiting, fatigue, loss of appetite, hair
loss, skin reactions.
b) Long term side effects: Infertility, cataracts, Secondary cancers, damage
to liver, lung, kidney, heart.
c) Graft versus host disease (GVHD).
d) Neurologic complications:
 Infections.
 Metabolic encephalopathy.
 Leukoencephalopathy.
e) Growth depravation.
f) Hypothyroidism.
g) Immune reconstitutions.
References:
1. Parthasarathy, K Nedunchalian, Gowri Shankar HC, Textbook of Balram chowdhary’s Pediatrics
Lecture notes, PEE PEE Publication, 2nd edition, Pg no. 290 – 313