approach

1. Approach to Extracorposcular Hemolytic
Anemia
Dr. Bikal Lamichhane
Internal medicine resident

2. Extracorpuscular defects
 those in which the RBCs are normal but are destroyed due to
 mechanical
 immunologic
 Infectious
 metabolic/oxidant damage.
These abnormalities are almost always acquired.
Exception is familial hemolytic-uremic syndrome (HUS; often referred
to as atypical HUS).

3. Etiology:-

4. Non-immune
Infection
•Intracellular organisms, e.g.
malaria
•Toxins, e.g. C. perfringens
Mechanical
•Prosthetic valves
•Microangiopathic, e.g. DIC,
HUS, TTP
•March haemoglobinuria
Chemical/physical
•Oxidative drugs,e.g. dapsone,
maloprim
•Copper (Wilson’s disease)
•Burns
•Drowning

5. Immune Hemolytic Anemias
 can arise through at least two distinct mechanisms.
1.when an antibody directed against a certain molecule (e.g., a drug)
reacts with that molecule, red cells may get caught in the reaction (the
so-called innocent bystander mechanism)
2.a true auto-antibody is directed against a red cell antigen, i.e., a
molecule present on the surface of red cells .

6.  Based on the Coombs test findings as well as on
the thermal characteristics and the antigenic specificities of the
autoantibodies. AIHA has been classified into subtypes.

7.  Warm Antibody AIHA
 more common type of AIHA.
 the auto-antibody reacts best at 37°C
 may be seen in isolation (and it is then called idiopathic) or as part of
a systemic auto-immune disorder such as systemic lupus
erythematosus (SLE)
 May be seen in chronic lymphocytic leukemia (CLL), after BMT; and
after solid organ transplantation entailing immuno-suppressive
treatment.
 As a side effect of the use of immune checkpoint inhibitors, such as
nivolumab, in patients with various types of cancer

8.  Once a red cell is coated by an autoantibody
 In most cases, the Fc portion of the antibody
will be recognized by the Fc receptor of macrophages, and this will
trigger erythrophagocytosis.
 Thus, destruction of red cells will take place wherever macrophages
are abundant, i.e., in the spleen, liver, and bone marrow.
 Spleen is the predominant site of red cell destruction.

9.  COLD AGGLUTININ DISEASE
 AIHA that usually affects the elderly.
 1. CAD is characteristically a chronic condition—in contrast to the abrupt
onset of warm antibody AIHA.
 Mediated by antibodies, usually IgM, which bind to the red cells at low
temperatures and cause them to agglutinate.
 May cause intravascular haemolysis if complement fixationoccurs.
 Can be chronic when the antibody is monoclonal,or acute or transient when
the antibody is polyclonal.

10.  The term cold refers to the fact that the autoantibody involved reacts with
red cells poorly or not at all at 37°C, whereas it reacts strongly at lower
temperatures.
 As a result, hemolysis is more prominent the more the body is exposed to
the cold.
 The antibody is usually IgM; usually it has
an anti-I specificity (the I antigen is present on the red cells of almost
everybody), and it may have a very high titer (1:100,000 or more has
been observed).
 The antibody is produced by an expanded B lymohocyte clone (a low-grade
mature B cell lymphoma) and sometimes the antibody concentration in the
serum is high enough to show up as a spike in plasma protein
electrophoresis, i.e., as a monoclonal gammopathy.

11. 

12.  Alloimmune haemolytic anaemia

Alloimmune haemolytic anaemia is caused by antibodies against
non-self red cells. It has two main causes, occurring after:

• unmatched blood transfusion.

• maternal sensitisation to paternal antigens on fetal cells
(haemolytic disease of the newbor).

13.  Non-immune haemolytic anaemia
• Mechanical heart valves. High flow through incompetent
valves or periprosthetic leaks through the suture ring
holding a valve in place result in shear stress damage.
• March haemoglobinuria. Vigorous exercise, such as
prolonged marching or marathon running, can cause red
cell damage in the capillaries in the feet.
• Thermal injury. Severe burns cause thermal damage to red
cells, characterised by fragmentation and the presence of
microspherocytes in the blood.

14. Microangiopathic haemolytic anaemia.
 Fibrin deposition in capillaries can cause severe red cell disruption.
 It may occur in a wide variety of conditions:
 Disseminated carcinomatosis,
 malignant or pregnancy-induced hypertension,
 haemolytic uraemic syndrome
 thrombotic thrombocytopenic purpura and
disseminated intravascular coagulation

15. Infection
 Plasmodium falciparum malaria .
 may be associated with intravascular haemolysis;
 Clostridium perfringens sepsis usually in the context of ascending
cholangitis or necrotising fasciitis, may cause severe intravascular
haemolysis with marked spherocytosis due to bacterial production
of a lecithinase that destroys the red cell membrane

16.  Chemicals or drugs
Dapsone and sulfasalazine cause haemolysis by oxidative
denaturation of haemoglobin.
 Denatured haemoglobin forms Heinz bodies in the red cells, visible
on supravital staining with brilliant cresyl blue.
 Arsenic gas, copper, chlorates, nitrites and nitrobenzene derivatives
may all cause haemolysis

17. Thank you