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Anaemia 2: Haemolytic And Haemoglobinopathies


Haemolytic Anaemia
This is anaemia due to destruction (lysis) of red blood cells before they
reach their natural life of 120 days. Intravascular lysis means that the
haemoglobin is destroyed in the circulation. Extravascular means that
cells are lysed by macrophages in the liver and spleen (where they are
normally broken down).
The presentation is that of anaemia. Hyperbilirubinaemia may develop
resulting in jaundice and gallstones. Splenomegaly and skeletal
abnormalities may develop with specific forms of this anaemia.
Investigation:
1. Anaemia: normocytic or mildly macrocytic
2. Reticulocytosis (stimulation of RBC regeneration)
3. Blood film: reticulocytosis (young red blood cells in the circulation),
spherocytes (no central pallor, sphere shaped, present in
spherocytosis and autoimmune haemolytic anaemia).
4. Bone marrow: normoblastic hyperplasia
5. Bile: Unconjugated hyperbilirubinaemia (hence it does not enter the
urine)
6. Free haemoglobin: haemogobinaemia, haemoglobinuria,
haemosiderinuria (renal tubular cells damaged and excreted),
absent haptoglobins (which normally mop up excess haemoglobin)
Haemolytic anaemia can be divided as follows:
Congenital
Membrane defect {hereditary spherocytosis}, enzyme defect {eg. G6PD
deficiency}, Hbg defect {sickle cell anaemia, thalassaemia}
Acquired
Immune {incompatible blood transfusion, autoimmune haemolytic
anaemia}. infection {eg malaria}. drugs/chemicals {eg dapsone/amyl
nitrate}, mechanical {prosthetic heart valve, microangiopathic
haemolytic anaemia}
Glucose 6 Phosphatase Deficiency
This condition is x-linked, hence only men can suffer from it. It is the
commonest RBC enzyme deficiency causing haemolysis. G6PD helps
protect against oxidative stress. It is normally asymptomatic, but crises
are provoked by:
Acidosis eg DKA
Infections
Oxidant drugs (antimalarials, sulfonamides, synthetic vitamin K
nitrofurans)
Fava beans: a classic for exams!
On investigation Heinz Bodies are seen on the blood film. These are
precipitates of oxidised, denatured Hbg cells that have had Heinz removed
by the spleen.

HEINZ BODIES
Automimmune Haemolytic Anaemia

In this disease RBCs are destroyed by an autoantibody which binds to RBC


membrane antigens. There condition is divided in to antibodies which are
most active in the cold or warm. A way of memorising the specific
antibody is to think of IgG representing "Great" heat, whilst IgM
represents "Mild" heat.
Warm (IgG)
This is the most common type, and results in severe anaemia. The
antibodies are optimally active at 37 degrees centigrade. Extravascular
haemolysis. Idiopathic or associated with lymphoma/SLE/chronic
lymphocytic leukaemia or drugs (methyldopa). On the blood film,
spherocytes, Reticulocytes are seen. Treatment is with steroids and
sometimes splenectomy.
Cold ("cold agglutin disease") (IgM)
These antibodies are optimally active at 4 degrees centigrade and they
cause RBC agglutination (RBCs sticking together mediated by
complement) and intravascular haemolysis in cold exposed parts of the
body. The condition may be idiopathic or associated with eg lymphoma.
On the blood film RBC agglutination is seen. Patients are advised to keep
warm, and chlorambucil is given, which deregulates lymphoid cells which
produce Igm.

AGGLUTINATED

RED BLOOD CELLS

The direct antiglobulin (Coombs) test can be used to diagnose


autoimmune haemolytic anaemia. Antiglobulin containing anti-IgG and
anti-complement is added to a washed suspension of patient's RBCs
suspended in normal saline. IgG or complement on the surface of the
membrane cause RBCs to agglutinate.

Haemoglobinopathies
These are problems with the synthesis of haemoglobin. The two
commonest types are:
Thalassaemia: disorders of the quantity of haemoglobin
Sickle cell anaemia: disorders of the structure of haemoglobin
Sickle Cell Anaemia
This comes up extremely frequently in written exam questions for some
reason. The disease is recessive.
Sickle cell anaemia remains common because in the carrier state it
protects against malaria. The carrier state is termed Sickle cell trait , and
denoted HbS (as opposed to the homozygous state of HbSS). Less than
50% of RBCs are sickle cells. It is of not much significance and has a
normal life expectancy although renal papillary necrosis (inability to
concentrate urine) is a complication.
The homozygous state is more severe with a life expectancy of about
40y. It has a variety of clinical manifestations. These can be remembered
using the mnemonic SICKLE :
S
Swellings {Painful transient. Hand and foot syndrome, dactylitis},
Splenic sequestration {occlusion of splenic vessels and splenomegaly.
Big spleen can take all blood supply. Treatment: splenectomy}
I
Infections {including osteomyelitis}, Infarctions {aseptic necrosis of

femoral head}
C
Chronic haemolysis {due to rigidity of RBCs}, Crises {vaso-occlusive
(acute episodes bone pain, worsening anaemia, pulmonary and
neurological compl's, precipitated by cold/dehydration/infections,
varying frequency weeks to months), Aplastic (parvovirus turns off
erythroid stem cells, cos half life anaemia}, Cholelithiasis (Gallstones)
K
Kidney
L
Lungs (Chronic chest syndrome)
E
Erection (priapism), Eye (retinopathy)
On investigation:
1.
2.
3.
4.

Anaemia: 6-10 g/dl


Blood film: reticulocytes, sickle cells, target cells
Sickle solubility test: Sickle S is insoluble in phosphate buffer.
Haemoglobin electrophoresis

SICKLE

SHAPED RED BLOOD CELL

Treatment is with penicillin and folic acid prophylaxis (folic acid is required
due to increased turnover of cells). Hydroxyurea is given, which
upregulates fetal haemoglobin. Acute episodes are managed with IV
fluids, oxygen, analgesia, antibiotics and blood transfusion. Bone marrow
transplantation can be curative.
Thalassaemia
This is decreased synthesis of either alpha or beta haemoglobin chains. It
also protects against Malaria.

TARGET

CELLS ARE SEEN IN THALASSAEMIA

Beta thalasaemia may be heterozygous (trait) or homozygous. The less


severe beta thalasseamia trait gives rise to mild anaemia although it is
usually asymptomatic. It is useful to diagnose to ensure that
innappropriate oral iron is not given, and to identify family members with
the condition.
The homozygous form - beta thalassaemia major - gives rise to severe
anaemia. Infants present in the first few months after birth (when fetal
haemoglobin does not contain beta chains). 80% of affected infants would
die without treatment. Treatment is with lifelong blood transfusions.
Desferrioxamine is given to reduce the iron excess that results from
transfusions. Folic acid supplementation is necessary. Splenectomy is
sometimes performed if the spleen becomes too large. Bone marrow
transplantation in early life may be curative.
The severity of alpha thalassaemia depends on how many of the alleles
is affected. Each of us has 4 alpha haemoglobin alleles.
1 or 2 chains affected
Asymptomatic or mild anaemia
3 chains affected: "HbH disease"

Increased beta chain synthesis gives rise to beta4 tetramers.


Presentation is with jaundice, hepatosplenomegaly, leg ulcers and
gallstones. A hypochromic microcytic anaemia is seen, with "golf ball"
dots on RBCs. Treatment is with folic acid, transfusions and splenectomy
4 chains affected: "Hb Barts Hydrops"
This causes intrauterine death
C o p y r i g h t

P a s s M E D ,

2 0 0 8 .

D i s c l a i m e r