HAEMOLYTIC ANEMIAS
Dr.Gireesh kumar.K.P
Hemolytic anemia
• Normal RBC life span – 120 days
• Hemolytic anemia (or haemolytic anaemia) is a form
of anemia due to hemolysis, the abnormal/premature
breakdown of red blood cells (RBCs), either in the blood
vessels (intravascular hemolysis) or elsewhere in the
human body (extravascular).
• Hemolytic anemias (HAs), may be inherited or acquired.
Causes
Intra Erythrocytic Hemolysis Extra Erythrocytic Hemolysis
Hereditary Autoimmune - Autoimmune hemolytic
RBC membrane defects – anemia (AIHA),Collagen vascular disease
Spherocytosis, Non immune
Elliptocytosis Hypersplenism
Enzyme defects -G6PD Deficiency, Infection – Malaria, toxoplasmosis,
Pyruvate Kinase deficiency mononucleosis(IMN), hepatitis
Hemoglobinopathies- Hepatic and renal disease,
Sickle cell disease Physical agents: Burns, cold exposure
Thalassemia Traumatic: Prosthetic cardiac valves,
march hemoglobinemia, DIC, graft
Acquired rejection
B12,Folate deficiency, Chemicals: Drugs and venoms(snake
bite)
Paroxysmal Nocturnal Hemoglobinuria
Malignancies: Particularly hematologic
neoplasia
Transfusion of incompatible blood
Hemolytic disease of the newborn
Thrombotic Thrombocytopenic Purpura
(TTP) and Hemolytic Uremic Syndrome
(HUS)
Coombs test
Direct coombs test can diagnose RBC binding IgG antibody or complement C3
present on RBC membrane. Patients RBC is incubated with antibodies to human
IgG and C3.If IgG or C3 is present agglutination occurs- It is a positive test.
Indirect coombs
Indirect coombs test can diagnose antibodies against RBCs in patient’s serum.
Patient’s serum is incubated with reagent RBCs. Then coombs serum with
antibodies to human IgG is added. If agglutination occurs IgG antibodies against
RBCs are present.
AUTO IMMUNE HEMOLYTIC ANEMIA (AIHA)
• Autoimmune hemolytic anemia is caused by
autoantibodies that react with RBCs at
temperatures ≥ 37° C (warm antibody hemolytic
anemia) or < 37° C (cold agglutinin disease).
“WARM Antibody” AIHA (80%)
• Warm antibodies act against RBCs best at > 370 C
• Warm antibodies are usually IgG (rarely IgM or IgA)
• More commonly seen in middle aged females
• In warm antibody hemolytic anemia, hemolysis occurs primarily in
the spleen and is not due to direct lysis of RBCs.
Types
Idiopathic (50%)
Secondary
Lymphoma, CLL, Myeloma
Solid tumors of lung, kidney, ovary, colon, thymus
SLE, Rheumatoid Arthritis, HIV, Ulcerative colitis
Drugs – Methyldopa, Mephenamic acid, penicillin
Clinical Features
Haemolytic anaemia, Jaundice, Shock due to severe haemolysis
Haemoglobinuria
Labs
Anemia: with a hemoglobin usually in the range of 7 to 10 g/dL
Peripheral smear – Spherocytosis, Reticulocytosis
Reticulocytosis in response to the hemolytic anemia
An elevated mean corpuscular hemoglobin concentration (MCHC), indicating
presence of spherocytes and/or an increase in the mean corpuscular volume (MCV)
indicative of reticulocytosis.
Direct Coombs Test – Positive in 98% (Coombs re-agent which contains antibodies
against human IgG, IgM and compliment)
Coombs-negative AIHA — In less than 3% of patients with warm agglutinin AIHA, the
direct Coombs test is negative
Coombs can be negative in
Rapid haemolysis
Lower levels of antibodies (Requires 200 antibody molecules to attach to each
RBC)
. IgA or IgE antibodies
Immune mediated thrombocytopenia (EVAN’s Syndrome - ES) also seen some
Reticulocytosis is a condition where there is an increase in reticulocytes, immature red blood cell.
times. Although usually described in children, adults may also have ES. In
Labs Coombs test positive
EVAN’s Syndrome - ES
• Immune mediated thrombocytopenia (EVAN’s
Syndrome - ES) also seen some times. Although usually
described in children, adults may also have ES. In
approximately half of the patients, no other immune
disorder is recognized, but in half it is associated with
SLE, common variable immune deficiency, autoimmune
lymphoproliferative disorder, or other immune disorders
Management
Prednisolone 1 mg /Kg starting dose
Response is seen in 70 – 80% in 3 weeks
Once haemoglobin becomes normal and bilirubin and LDH falls to normal values it
can be slowly reduced to 10 mg /day
Blood transfusions in severe shock
Splenectomy in “not responding” patients
Other immune suppressive agents
Azathioprine 1 – 2 mg/Kg
Cyclophosphamide 2 mg / Kg
Rituximab - The monoclonal anti-CD20 antibody rituximab is a chimeric
monoclonal antibody directed against the B cell surface protein CD20. Dose:
IV: 375 mg/m2 once weekly for 4 doses (may continue systemic corticosteroids
along with rituximab); a second course may be administered for relapse
“COLD Antibody” AIHA (20%)
Cold antibodies acts against RBCs best at < 370C. The higher the temperature (ie, the
closer to normal body temperature) at which these antibodies react with the RBC, the greater
the hemolysis.
Cold antibodies are usually IgM types
The hemolysis occurs largely in the extravascular mononuclear phagocyte system of the liver
and spleen.
Types
Chronic - It may be idiopathic or seen with lymphocytic neoplasia or paraneoplastic
syndrome
Transient- In infections like Mycoplasma Pneumoniae or Infectious Mononucleosis
Cold AIHA
Clinical Features
On exposure to cold / or swallowing of cold food, they may develop haemolysis and
intravascular agglutination (ACROCYANOSIS)
ACROCYANOSIS:- Purpling of extremities, ears, nose, due to agglutination of blood
in veins, and it may clear on warming
Treatment
Treat primary disease
Keep extremities warm
Corticosteroids in primary
Blood transfusion in severe cases – use only warm blood (370C)
Differentiating Warm or Cold antibodies in AIHA
• Once AIHA has been diagnosed by the Coombs test, testing should
differentiate between warm antibody hemolytic anemia and cold agglutinin
disease as well as the mechanism responsible for warm antibody hemolytic
anemia. This can be made by observing the pattern of the direct Coombs
reaction. Three patterns are described:
– The reaction is positive with anti-IgG and negative with anti-C3. This pattern is common
in idiopathic AIHA and in the drug-associated or alpha-methyldopa-type of AIHA, usually
warm antibody hemolytic anemia.
– The reaction is positive with anti-IgG and anti-C3. This pattern is common in patients
with SLE and idiopathic AIHA, usually warm antibody hemolytic anemia, and is rare in
drug-associated cases.
– The reaction is positive with anti-C3 but negative with anti-IgG. This pattern occurs in
cold agglutinin disease(where the antibody is most commonly an IgM). It can also occur
in warm antibody hemolytic anemia when the IgG antibody is of low affinity, in some drug-
associated cases, and in PCH.
