Dr Abdullah Ansari MBBS, MD Medicine Aligarh Muslim University Clinical case Hemolytic Anemia Intravascular vs extravascular hemolysis Classification of hemolytic anemia Approach to hemolysis Patient history Clinical features Peripheral blood smear Investigation Treatment

1. Approach to
Hemolytic Anemia
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University

2. Clinical Case
Zohra Begum
40 yr/ Female
Chief complains:
• yellowing of skin, fatigue, effort intolerance – 5
months
• ulcer at back – 3 months

3. Examination
• Pallor +nt, Icterus +nt, LAD -nt
• CNS : WNL
• CVS : WNL
• Respiratory : WNL
• P/A : splenomegaly +nt

4. Investigations
• CBC : Hb 3.1 gm/dl, TLC 7100, platelets 75000
• RFT : BUN 19, Cr 1.73
• LFT : AST 21, ALT 26, ALP 18, Bil 4.5 (Indirect
3.5, direct 1)
• Urine R/M : WNL

5. • Reti count : 3.6%
• LDH : 1062 U/L
• Direct Coomb’s : +ve
• ANA : +ve

6. Diagnosis
Autoimmune hemolytic
anemia

7. Hemolytic anemia
Hemolytic anemia : the abnormal breakdown of
red blood cells (RBCs), either in the blood
vessels (intravascular hemolysis) or elsewhere
in the human body (extravascular)

8. • Hemolysis indicates shortening of normal red
cell lifespan of 120 days
• To compensate, the bone marrow increases its
production, expanding the marrow volume,
and releasing reticulocytes prematurely
• Anemia occurs if the rate of destruction
exceeds this increased production rate

9. • Red cell destruction causes a modest rise in
unconjugated bilirubin
• Increased reabsorption of urobilinogen from the
gut results in an increase in urinary urobilinogen
• Red cell destruction releases LDH into the serum
• The bone marrow compensation results in a
reticulocytosis, and sometimes nucleated red cell
precursors appear in the blood

10. Extravascular hemolysis
• Red cell destruction occurs in the
reticuloendothelial cells (liver or spleen)
• Free hemoglobin is not released in the plasma
• To confirm, patient’s red cells is labelled with
51chromium, and compared with body surface
radioactivity counting

11. Intravascular haemolysis
• Free hemoglobin is released in plasma which binds to
Haptoglobin, an α2-globulin produced by the liver,
resulting in fall in its levels
• Once haptoglobins are saturated, free hemoglobin is
oxidised to form methemoglobin, which binds to
albumin to form methemalbumin, detected
spectrophotometrically in the Schumm’s test
• Methemoglobin is degraded and any free haem is
bound to hemopexin
• If all the protective mechanisms are saturated, free
hemoglobin may appear in the urine (hemoglobinuria)

13. Approach to Hemolytic Anemia
Plan of Action:
1. History and clinical examination
2. Peripheral blood smear
3. Confirm hemolysis
4. Whether hemolysis is intra or extravascular
5. Determine the etiology

14. Patient History
• Acute or chronic
• Medication/Drug precipitants
– G6PD
– AIHA
• Family history
• Concomitant medical illnesses
• Clinical presentation

15. Clinical features of hemolytic anemia
• Pallor or anemia
• Jaundice/ indirect hyberbilirubinemia
• Splenomegaly
• Gall stones
• Dark colored urine
• Leg ulcers

16. Peripheral Blood Smear
• Determines the etiology of hemolysis
• Intravascular hemolysis may reveal red cell
fragmentation (i.e. schistocytes, helmet cells),
whereas spherocytes indicate extravascular
hemolysis
• Polychromasia and nucleated RBCs are
indicators of increased erythropoiesis

17. Investigation indicating haemolysis
• ↓Haemoglobin
• ↑Unconjugated bilirubin
• ↑Lactate dehydrogenase
• ↑Reticulocytes
• ↑Urinary urobilinogen

18. Additional features of intravascular
hemolysis
• ↓Haptoglobin
• ↑Methaemalbumin
• Positive urinary haemosiderin
• Haemoglobinuria

20. Laboratory Evaluation of Hemolysis
Extravascular Intravascular
HEMATOLOGIC
Routine blood film
Reticulocyte count
Bone marrow
examination
Polychromatophilia
Erythroid
hyperplasia
Polychromatophilia
Erythroid
hyperplasia
PLASMA OR SERUM
Bilirubin
Haptoglobin
Plasma hemoglobin
Lactate dehydrogenase
Unconjugated
/ Absent
N/
Unconjugated
Absent
URINE
Bilirubin
Hemosiderin
Hemoglobin
+
0
0
+
+
+ severe cases

21. Autoimmune Hemolytic Anemia
• Autoimmune hemolytic anemia (AIHA) results
from autoantibodies targeted to antigens on
the patient's own RBCs, resulting in
extravascular hemolysis

22. Classification
• Warm AIHA antibodies interact best with
RBCs at 37°C
• Cold AIHA antibodies are most active at
temperatures below 37°C and almost always
fix complement

23. Warm antibody AIHA
• Usually an IgG autoantibody
• Causes:
– 50% Idiopathic
– secondary causes:
1.Lymphoid neoplasm: CLL, Lymphoma, Myeloma
2.Solid Tumors: Lung, Colon, Kidney, Thymoma
3.Connective Tissue Diseases: SLE, RA
4.Drugs: Alpha methyldopa, Penicillin, Chloroquine
5.UC, HIV

24. Cold antibody AIHA
• Usually an Ig M autoantibody
• Causes:
– Acute form : Mycoplasma, Infectios Mononucleosis
– Chronic form : Lymphoma, CLL, Waldenstrom
macroglobulinemia, Idiopathic (50% cases)
• Paroxysmal cold haemoglobinuria: very rare &
associated with viral or bacterial infection, IgG
Donath–Landsteiner antibody against the P antigen

25. Diagnostic Testing
• Laboratory data : anemia, reticulocytosis,
elevated LDH, decreased haptoglobin, and
indirect hyperbilirubinemia
• Peripheral blood smear : spherocytes, occasional
fragmented RBCs, polychromasia, and nucleated
RBCs
• The hallmark of diagnosis is by a positive DAT
(direct Coombs test)
• If secondary AIHA is suspected, a workup for the
underlying cause should be performed

26. TREATMENT
• Initial therapy aimed at correcting complications
from the hemolytic anemia
• Definitive therapy should include identification
and treatment of any underlying cause
• RBC transfusions may exacerbate hemolysis with
hemolysis of transfused cells
• In life-threatening circumstances, transfusion of
universal donor (O negative) blood is appropriate

27. • Glucocorticoid such as prednisone 1 mg/kg/d
is effective in 70- 80% of patients
• When hemolysis has abated, glucocorticoids
can be tapered over 2-3 months
• Second-line treatments include splenectomy,
and rituximab, a monoclonal antibody against
CD20 antigen expressed on B cells

28. • Additional immunosuppressants azathioprine,
cyclophosphamide, cyclosporine, and
mycophenolate mofetil
• Treatment for relapsed/refractory cases
includes IVIG, danazol, plasma exchange,
alemtuzumab, & high-dose cyclophosphamide