The document describes a case of an 18-year-old female presenting with generalized tiredness, fever, nausea and body pain for one week with a history of similar episodes over the past two years. On examination, she was found to have pallor, splenomegaly, and laboratory investigations revealed severe anemia, hyperbilirubinemia and a positive sickling test. She was diagnosed with homozygous sickle cell anemia.

1. AN APPROACH TO HEMOLYTIC
ANAEMIA-
INTERESTING CASE OF ANEMIA
DR. ASHWANT KUMAR MD(GEN MED)
JANANIE IYER CRMI
JOSHNA JOHNSON CRMI

2. 1. 15 year old male with recurrent febrile episodes has come with Right Hand
swelling,pain and fever for 3 days.
2. 18 year old female with recurrent episodes of jaundice,anemia and fever.
3. 28 year old male, married ,presented with priapism and jaundice.
4. 25 year old female with pallor, sudden onset of chest pain and breathlessness and
fever
5. 14 year old boy with sudden onset weakness of Left upper and Lower limb
6. 26 year old male with chest pain and breathlessness.ECG revealing inf wall MI.
7. A 32 year old female with jaundice and Right Hypochondrial pain associated with
vomiting and fever.

3. CHIEF COMPLAINTS
A 18 YEAR OLD FEMALE , NATIVE OF ODISHA, CAME WITH
COMPLAINTS OF
• GENERALIZED TIREDNESS FOR 2 WEEKS
• FEVER , NAUSEA AND BODY PAIN FOR PAST 1 WEEK

4. HISTORY OF PRESENTINGILLNESS
• Generalised tiredness – 2 weeks
• Fever – 1 Week,
 High grade
 Intermittent type
 Associated with chills and rigor
• H/O Myalgia – 1 week
• H/O Abdominal discomfort – 1 week
• H/O Headache - 2 days

5. • No history of burning micturition
• No history of cough
• No history of chest pain
• No history of loss of vision
• No history of joint swelling
• No history of yellowish discoloration of skin
• No history of breathlessness

6. PAST HISTORY
• H/O SIMILAR COMPLAINTS , 2 MONTHS BACK FOR WHICH SHE WAS
ADMITTED AND SEEKED TREATMENT IN A PRIVATE HOSPITAL, WHOSE
DETAILS ARE NOT AVAILABLE.
• H/O RECURRENT FEVER EPISODES FOR THE PAST 2 YEARS
• NO H/O PREVIOUS MI, CEREBROVASCULAR ACCIDENT, TIA OR SUDDEN
LOSS OF VISION.
• NOT A KNOWN CASE OF DIABETES MELLITUS, HYPERTENSION, THYROID
DISORDERS, EPILEPSY, TUBERCULOSIS, BRONCHIAL ASTHMA
• NO H/O CHRONIC DRUG INTAKE

7. MENSTRUALHISTORY
• LMP-9/3/2023
• 4/30 DAYS,REGULAR PERIODS,ASSOCIATED WITH ABDOMINAL
PAIN,NO H/O PASSAGE OF CLOTS
MARITAL HISTORY
 Unmarried

8. PERSONAL HISTORY
• MIXED DIET
• NO H/O SUBSTANCE ABUSE
• NORMAL BOWEL AND BLADDER
FAMILY HISTORY
 No history of similar complaints in family
 No history of consanguinous marriage in family

9. SUMMARY
• A 18 YEAR OLD FEMALE WITH NO KNOWN CO MORBIDITIES WITH
COMPLAINTS OF GENERALIZED TIREDNESS, FEVER FOR ONE WEEK
WITH SIMILAR FREQUENT EPISODES IN PAST 2 YEARS.

10. GENERAL EXAMINATION
• CONSCIOUS
• ORIENTED
• AFEBRILE
• THIN BUILT, POORLY NOURISHED
• PALLOR(+)
• NO ICTERUS
• NO CYANOSIS
• NO GENERALISED LYMPHADENOPATHY
• NO BILATERAL PITTING PEDAL EDEMA
Height :157cm
Weight : 30 kg

11. VITALS
• BP: 100/60
• PR: 98BPM
• SPO2 : 98% IN ROOM AIR
• RR:18/MIN
• TEMP: 98.4 F

12. SYSTEMIC EXAMINATION
CVS - S1 ,S2 (+), NO MURMURS
RS - B/L AIR ENTRY (+)
NO ADDED SOUNDS
P/A - SOFT
SPLEEN PALPABLE 4 CM FROM LEFT COSTAL MARGIN
SPLENOMEGLY(+)
CNS – NO FOCAL NEUROLOGICAL DEFICIT

13. INVESTIGATIONS
CBC :
• WBC -48.31
• RBC -2.84
• HGB -6.4
• PLT -116
RBS - 109 MG/DL
LFT :
• TOTAL BILIRUBIN : 2.4
• DIRECT BILIRUBIN : 1.6
• INDIRECT BILIRUBIN :
0.8
• SGOT : 401
• SGPT : 302
• T.P : 7.2
• ALP :66

14. • Renal Function
Tests : S. Urea - 21 mg/dl
S. Creatinine - 1.0 mg/dl
• Serum electrolytes : Na+ - 127 mmol/l
K+ - 4.0 mmol/l
• Serum Calcium :8.5 mg/dl
• ESR - 29
72
• HbSAg - Negative
• Anti – HCV - Negative
• HIV I & II - Negative
• Blood group - B+

15. Fasting Lipid Profile:
Total Cholesterol – 114 mg/dl
Triglycerides - 215 mg/dl
HDL - 31 mg/dl
LDL - 40 mg/dl
VLDL - 45 mg/dl
Urine Routine
Albumin - Nil
Sugar - Nil
USG ABDOMEN
Gall Bladder - Distended
Spleen - Enlarged,14cm with altered echotexture
Ovaries - Right ovary –normal
- Left ovary – shows simple cyst measuring
5*3cm

16. DIAGNOSIS ???

18. Serum LDH - >1000 IU/ml
Direct Coombs Test – Negative
Dengue Serology
NS 1 – Positive
PERIPHERAL SMEAR:
RBC - Show severe anisopoikilocytosis and are microcytic and
hypochromic macrocytes. Target cells (+)
- Sickle cell (+)
- Nucleated Rbc – 25/100 WBC
WBC : TC – Increased.
Impression :
- feature suggestive of hemolytic anemia

19. HEMOGLOBIN
ELECTROPHORESIS
RESULT OF CAPILLARY ELECTROPHORESIS
HBF 23.6
HBA -
HBA2 2.4
HB S 74.0
HEMOGLOBIN ELECTROPHORESIS IS
SUGGESTIVE OF HOMOZYGOUS HBS
DISEASE

20. INTERPRETATION :

21. FINAL DIAGNOSIS
HEMOLYTIC ANAEMIA –
SICKLE CELL DISEASE

22. 1. 15 year old male with recurrent episodes of fever has come with Right
Hand swelling,pain and fever for 3 days.
- Dactylitis
2. 18 year old female with recurrent jaundice,anemia and fever.
- Hemolytic Crisis
3. 28 year old male,married with priapism and jaundice.
- Vaso – Occlusive Crisis
4. 25 year old female with pallor, sudden onset of chest pain and
breathlessness and fever
- Acute Chest Syndrome
5. 14 year old boy with weakness of Left and Right Lower limb
- Acute Cerebrovascular Accident
6. 26 year old male with chest pain and breathlessness.ECG revealing
inferior wall MI
- Acute Myocardial Infarction
7. A 32 year old female with jaundice and Right Hypochondrial pain
associated with vomiting and fever.
- Cholelithiasis

23. ? Prescription of sickle cell anaemia patient
? Use of hydroxyurea.
? Indications of Splenectomy in SCA.
? Conditions that aggravate sickling.
? Investigation of choice.
? Treatment of choice.
? When to suspect Sickle Cell Disease?
COMMON QUESTIONS

24. ? Sickle cell anaemia and Marriage.
? Endemic areas in India for sickle cell anaemia.
? Why do Sickle cell anaemia patients have mild
hypoxemia
? Why Splenomegaly seen in SCD?
? Autosplenectomy?
? Why Jaundice seen in SCD?

25. DEFINITION OF ANAEMIA
• ANAEMIA IS DEFINED AS AN INSUFFICIENT RED BLOOD CELLS MASS TO
ADEQUATELY DELIVER OXYGEN TO PERIPHERAL TISSUES.
• IT MAY BE DUE TO REDUCED PRODUCTION OR INCREASED
DESTRUCTION OR BOTH
• ACCORDING TO WHO: HEMOGLOBIN OF
• <13 IN ADULT MALE
• <12 IN ADULT NON PREGNANT FEMALE
• <11 IN PREGNANT FEMALE
IS DEFINED AS ANAEMIA.

26. Approach to Anaemia:
Clinical symptoms of Anaemia/ Hemoglobin below the
above stated values
Do a peripheral smear and Reticulocyte
count
Reticulocyte Count:
It provides information about kinetics of red cell production in
response to anaemia. It is done manually by using supra vital stains
like Brilliant cresyl bule/ New methylene blue.
Calculate Reticulocyte Production Index (RPI): It is the corrected
reticulocyte count that accounts fpr reticulocytes in all
developmental stages.
Based on RPI, Anaemia can be classified into two broad types
Hypoproliferative Anaemia, If RPI <2
Hyperproloferative Anaemia , If RPI >2.5
2

27. Hypo proliferative Anaemia
Based on MCV values it can be divided
into 3 types
Microcytic
If MCV <80 fl
Normocytic
If MCV from 80-
99fl
Macrocytic
If MCV > 100
fl
• Iron Deficiency Anaemia
• RDW - > 15%
• Mentzer Index >13
• Microcytic,
Hypochromic RBC
• Anisopoikilocytosis
• Thalassemia Trait
• RDW – Normal limits
• Mentzer Index <13
• Sideroblastic Anaemia
• Elevated S. Ferritin
and S.Fe
• TIBC – low
• Pappanheimer
bodies
• Lead poisoning
• Anaemia of
chronic disease
• Renal failure
Megaloblastic
MCV may reach >120
Megaloblasts (+)
Non
Megaloblastic
MCV >100 fl
• B12 deficiency
• Folic acid deficiency
• Thiamine deficiency
• Orotic Aciduria
• Hypothyroidi
sm
• Alcoholics

28. Hyperproliferative Anaemia
Inherited Acquired
• Hemoglobinopathies
• Thalassemia
• Sickle Cell Anaemia
• RBC Membrane Defects
• Hereditary
Spherocytosis
• Hereditary
Elliptocytosis
• Metabolic Pathway defects
• G6PD defects
• Pyruvate Kinase
deficiency
• 5’ Nucleotidase
deficiency
Immune Non - Immune
• Auto Immune
• Warm Ab AIHA
• Cold Ab AIHA
• Paroxysmal Cold
hemoglobinuria
• Alloimmune
• Hemolytic
transfusion
reactions
• Drug Induced
• High dose IV
penicillins
• Quinidine
• Rifampicin
• Isoniazid
• Methyl dopa
• Procainamide
• Microangiopathic
Hemolysis
• Macroangiopathic
Hemolysis
• PNH
• TTP
• HUS

29. Hyperproliferative Anaemia
Intravascular Hemolysis
• Reticulocytosis
• High coloured urine
• Elevated LDH
• Low Haptoglobin
• Sensitive marker
• Last marker to be
corrected
Extravascular Hemolysis
• Occurs in Reticuloendothelial
cells
• Triad of Anaemia, Jaundice,
Splenomegaly
• Peripheral smear reveals
Reticulocytosis, Fragmented
cells,
Schistocytes.

31. SICKLE CELL ANAEMIA
• It is a Autosomal Recessive hereditary disorder of hemoglobin characterised by defective
hemoglobin synthesis called sickle hemoglobin
• Point mutations at 6th position of Beta globin chain.
• Glutamic acid is replaced by Valine  HbS  this alters the solubility of hemoglobin
• Dehydrated HbS molecules are insoluble and polymerise to form pseudocrystalline
tactoids  RBC become rigid and deformed
SICKLE CELL SYNDROMES
1. Heterozygous state for hbS
• Sickle cell trait
• Asymptomatic carrier state
• Only 40% of Hb is HbS
2. Homozygous state for HbS
• >80% of Hb is HbS
3. Compound Heterozygous
• Both B globin chains having different abnormalities – Hb SC, HbS Thalassemia

33. SCA – PATHOGENESIS
Deoxygenated HbS molecules undergo
aggregation and polymerisation
REVERSIBLE SICKLING:
Initially sickling is a reversible
phenomenon
With oxygenation, HbS depolymerises
and cell shape normalises
IRREVERSIBLE SICKLING
Repeated episodes of Sickling causes
membrane damage.
This makes cells permanently sickled.

34. SICKLE CELL ANAEMIA MORPHOLOGY
CHRONIC HEMOLYSIS, HYPERBILIRUBINEMIA, MICROVASCULAR
OCCLUSIONS, INFARCTS
BONE MARROW EXPANSION  BONE RESORPTION AND SECONDARY
NEW BONE FORMATION  PROMINENT CHEEKBONES AND CHANGES
IN SKULL BONES (CREW – CUT APPEARANCE ON X-RAY)
SPLEEN
EARLY PHASE – SPLENOMEGALY
LATE PHASE – PROGRESSIVE SHRINKAGE OF SPLEEN DUE TO AUTOSPLENECTOMY

35. • Peripheral Smear
• Sickle cells and target cells
• Features of splenic atrophy – Howell Jolly Bodies
• Sickling Test – Mixing the blood with sodium
metabisulfite
• Reticulocytosis
• Hyperbilirubinemia

36. CLINICAL FEATURES
• CHRONIC HEMOLYTIC ANAEMIA
• EPISODES OF APLASTIC CRISIS
• VASO-OCCLUSIVE CRISIS – EPISODES OF HYPOXIC INJURY AND
INFARCTION
• INCREASED SUSCEPTIBILITY TO INFECTIONS DUE TO
• IMPAIRED SPLENIC FUNCTION
• SEQUESTRATION CRISIS

38. MANAGEMENT
• TIMELY IMMUNISATION AGAINST STREPTOCOCCUS PNEUMONIAE, NEISSERIA
AND HEMOPHILUS.
• BLOOD TRANSFUSIONS
• REPEATED TRANSFUSIONS
• EXCHANGE TRANSFUSIONS
• HYDROXYUREA (10-15 MG/KG/DAY) – INCREASES HBF
• SENICAPOC – GARDOS CHANNEL INHIBITOR
• VOXELOTOR – HEMOGLOBIN S POLYMERISATION INHIBITORS BY STABILISING
HBS.
• ACUTE PAINFUL CRISIS:
• IV FLUIDS, OXYGEN, ANTI MICROBIAL AGENTS, ANALGESIA