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Hemolytic Disease

HEMOLYTIC DISEASE
Q&A COUNT: 49*


 THALASSEMIA:
Thalassemia - classification
Minor - Intermediate - Major
Major presents at 6 months with Hb less than 5g%
Intermediate type presents with Hb 6-7g%
Minor type is a carrier and only mild anemia occurs

Pathogenesis of Thalassemia
Defective synthesis of hemoglobin beta chain - less Hb - less oxygen carrying capacity
Also, abnormal Hb forms irregular clumps which results in premature hemolysis of RBC's. Results in Hemolytic Anemia*

Due to Hypoxia, 3 key events takes place:
  1. Widening/expansion of medulla in bones
  2. Growth retardation
  3. Increased Extramedullary hematopoiesis

Why age of onset is 6 months in T.major?
HbF persists till 3-4 months of age

What is Endemic Thalassemia?
Occurs at Rajasthan and West Tamilnadu (Salem) (high prevalence)

3 Key events in Pathogenesis of Thalassemia due to Hypoxia:
  1. Widening/expansion of medulla in bones
  2. Growth retardation
  3. Increased Extramedullary hematopoiesis
All these 3 can be prevented by maintaining Hb level at 10-12 g/dl

Name some Complications of Thalassemia:
  1. Anemia
  2. Iron Overload (due to blood transfusion)
  3. Gallstones

What is Diamond Blackfan anemia? What is its special feature? 
It is a congenital hypoplastic failure of bone marrow, with onset within first year of life
Special feature - Triphalangeal thumb

Methods - Intra-uterine diagnosis of Thalassemia done by:
Chronic Villus sampling
PUBS

There will be Motor milestones delay in Thalassemia, not other milestones delay. Why?
Low Hb levels results in lethargy - baby shows inability to carry out motor activities. Thus, there will be motor milestones delay*

Simple Algorithm of approach to hemolytic anemia 


EXAMINATION:
Describe Hemolytic or Chipmunk facies
1. Maxillary hyperplasia
2. Prominent parietal eminence
3. Occipital bossing
4. Prominent malar bones
5. Widely spaced eyes
6. Depressed nasal bridge

Criteria for Hypertelorism?
Using Canthal Index
Canthal Index = (Distance between inner canthus/ Distance between outer canthus) x 100
Normal Canthal index = 33-38
In Hypertelorism, canthal index will be >38
Also seen in Thalassemia*

What are the signs of Iron Overload?
  1. Koilonychia
  2. Leg ulcers
  3. Hyperpigmented skin
  4. Hepatomegaly

How to differentiate if hepatomegaly occurs due to overload of IRON or hemolytic anemia itself??
First learn the Approach to palpable liver.
Usually, liver palpable upto 2 cm below costal margin.
But, if palpable for >5 cm: it can be still either normal pushed down liver or Hepatomegalg
Now - Check for CONSISTENCY in case of hepatomegaly. It will be HARD in consistency (in case of IRON deposit)
Or FIRM in consistency in case of hemolytic anemia (due to Extramedullary hematopoiesis)

Tanner staging to be done for cases >9 years of age - Why?
As Gonads are affected by Iron overload
Tanner staging is to asses development of secondary sexual characters

Apical impulse in a case of Thalassemia
Due to anemia:
Hyperdynamic impulse
Cardiomegaly can cause apical impulse shift


SPLENECTOMY:
Age to do Splenectomy
Normally done after 6 years

Indications for Splenectomy less than 6 years:
  1. Pancytopenia
  2. Recurrent transfusion, but child is not improving
  3. Hypersplenism due to transfusion >200 ml/kg/year

Measures before and after splenectomy:
Before - Vaccines for Pneumococcus, Meningococcus and H.influenza
Do surgery 4 weeks after vaccination
After surgery - Prophylaxis (as there is increased risk of CAPSULATED organism infection)

Types of Splenectomy:
  1. Elective splenectomy (did after completing immunization)
  2. Emergency splenectomy

Name some Post operative complications of Splenectomy:
"SPLENECTOmy"

S - Subphrenic abscess, Subphrenic hematoma
P - Pancreatitis, Pancreatic fistula, Pneumonia
L - Left Lower Lobe Atelectasis (most common)
E - Effusion (Pleural effusion)
N - Nucleated RBC & Nuclear remnant (Howell Jolly bodies)
E - Enlargement of Gastrium
C - Cyst (Pseudocyst)
T - Thrombo-embolic (DVT/Portal vein Thrombosis)
O - OPSI (Overwhelming Post Splenectomy Infection) (dangerous)


IRON OVERLOAD:
Iron Overload sites in the body:
  1. Liver (hepatomegaly)
  2. Heart (failure)
  3. Eye
  4. Basal Ganglia
  5. Gonads
  6. Pancreas
  7. Parathyroid (seizures)
  8. Pituitary (causes growth retardation and diabetes)

TESTS FOR IRON OVERLOAD
  1. Serum Ferritin - overload dose >1000 mg/dl (ideally checked 1 year after transfusion and once every year afterwards)
  2. Echo - once a year
  3. TFT - once a year
  4. PTH, Vitamin D, Calcium profile
  5. Blood sugar
  6. Gonadogens - for gonadal dysfunction

Treatment for Iron Overload:
DESFERROXIME - Painful injection
Injection Dosage: 40-60 mg/kg/day over 8-12 hours for 5-6 days per week
(Or)
DEFARASIROX
Oral dose maximum: 30 mg/kg/day
Orally taken under EMPTY stomach in early morning (dissolved in water)

INVESTIGATIONS IN THALASSEMIA:
What is NESTOFT?
Naked Eye Single Tube Osmotic Fragility Test

Frequency to test for Iron overload
Serum Ferritin -Ideally checked 1 year after transfusion and tested once per year
ECHO and TFT - yearly screening

DD for Microcytic hypochromic anemia
1. Iron deficiency anemia
2. Thalassemia
3. Lead poisoning

List of Investigations in  a case of Thalassemia
  1. CBC - Anemia, Leukocytosis (due to extramedullary hematopoiesis)
  2. PB smear - microcytic hypochromic anemia, basophilic stippling, nucleated RBC
  3. LFT - bilirubin slightly high, enzymes normal
  4. Reticulocyte count - increased
  5. X ray Skull - Hair on end or Crewcut Appearance, maxillary prominence, crowding of teeth and thinning of cortex (due to bone marrow expansion)
  6. CXR - to rule out cardiomegaly
  7. Hb electrophoresis
  8. NESTOFT - Naked Eye Single Tube Osmotic Fragility Test

For other DD:
  1. Coombs test - for autoimmune hemolytic anemia
  2. Sickling test
  3. G6PD enzyme - for deficiency
  4. Pyruvate kinase enzyme - for deficiency

For IRON overload:
  1. Serum Ferritin - overload dose >1000 mg/dl (ideally checked 1 year after transfusion and once every year afterwards)
  2. Echo - once a year
  3. TFT - once a year
  4. PTH, Vitamin D, Calcium profile
  5. Blood sugar 
  6. Gonadogens - for gonadal dysfunction

THALASSEMIA - TREATMENT:
What are the anemias which require BLOOD TRANSFUSIONS?
1. Sickle cell anemia
2. Aplastic anemia
3. G6PD deficiency
4. PK deficiency (Pyruvate kinase)
5. Leukemia
6. Osteopetrosis

Normal amount of blood transfusion
180-200 ml/kg/year (More than this can cause HYPERSPLENISM, which is an indication for splenectomy)

Goal of Thalassemia Management
To maintain Hb level (10-12 mg/dl)

Why Hb level should be maintained at 10-12 mg/dl?
At this level:
There is no extramedullary hematopoiesis
There is normal growth

What is Hypertransfusion?
Hb maintained at level of 10-12 g%

What is Super transfusion?
Hb maintained at level of 12-14 g%

What is Hypotransfusion or Low transfusion?
Hb maintained at level of 6-10 g%

Intervention for different Hb level:
Transfuse 1 Unit of blood for Hb 9 g%
Transfuse 2-3 Units of blood for Hb 6 g%
Final Hb after transfusion in both cases is 12 g%

 Volume of Packed and Whole blood transfusion
Packed cell transfusion - 10 ml/kg
Whole blood transfusion - 20 ml/kg

What is NEO CELL TRANSFUSION?
Only young RBC with more lifespan are transfused
This is to reduce frequency of blood transfusion
Not done in India

Frequency of normal RBC blood tranfusion - once in 21 days

Advantage of Leukocyte depleted stored RBC?
To avoid adverse reaction due to transfusion (due to WBC derived antibodies)

Drug to increase HbF
HYDROXY UREA (minor role in treatment of Thalassemia)

Definitive treatment for Thalassemia
Stem Cell Transplantation

Genetic counselling in Thalassemia
Next baby can be affected

Nutritional counselling in Thalassemia:
TAKE IRON FREE DIET TO PREVENT IRON OVERLOAD
Avoid Jaggery, Dates, Ragi
Supplements - Vitamin C, Vitamin B9, Vitamin E
Drinking Tea along with food is shown to avoid absorption of iron from diet (to prevent Iron overload)

Diet advice in Thalassemia
TAKE IRON FREE DIET TO PREVENT IRON OVERLOAD
Avoid Jaggery, Dates, Ragi
Supplements - Vitamin C, Vitamin B9, Vitamin E
Drinking Tea along with food is shown to avoid absorption of iron from diet (to prevent Iron overload)

SICKLE CELL ANEMIA:
Pathophysiology of Sickle cell anemia & Name some sickle cell crisis
Management of Sickle cell crisis
  1. Correct Dehydration first (IV fluids)
  2. Correct acidosis
  3. Manage Pain
  4. Hydroxyurea - to increase HbF

Advice for a sickle cell anemia patient
AVOID ACIDOSIS producing condition acts like Exercise
This precipitates SICKLE CELL CRISIS