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
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)
12.
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
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