Page 328 - Concise Pathology for Exam Preparation ( PDFDrive )

12 Haematology 313

Bone Marrow
Mild erythroid hyperplasia.
Haemoglobin Electrophoresis
HbA 2 increased (3.6–9%; normal 1–3.5%)
Osmotic Fragility Test
Shows decreased osmotic fragility

Q. Write briefly on paroxysmal nocturnal haemoglobinuria (PNH).

Ans. PNH is the only example of an acquired defect in red cell membrane. It is character-
ized by chronic haemolytic anaemia with intermittent haemoglobinuria. It may be associ-
ated with aplastic anaemia, myelodysplastic syndrome and rarely acute leukaemia.

Pathology
• Mutation in phosphatidylinositol glycan A (PIGA) gene that codes for glycosyl-phospha-
tidylinositol (GPI) protein, which acts as an anchor of GPI-linked proteins to the cell
membrane.
• GPI-linked membrane proteins regulate complement factors and are absent in PNH.
These are
• CD55 or decay-accelerating factor
• CD59 or membrane inhibitor of reactive lysis
• C8-binding protein (homologous restriction factor)
GPI-linked proteins interact with C3b and C4b to dissociate the convertase complexes
of both classic and alternative complement pathways thus stopping amplification of activa-
tion by complement. RBCs, platelets and granulocytes are more sensitive to complement
lysis when these proteins are absent.

Laboratory Diagnosis
General Blood Parameters
• Evidence of intravascular haemolysis
• Decreased Hb, RBC, WBC and platelet counts (pancytopenia)
• Increased reticulocyte count and occasionally raised HbF
Peripheral Blood Smear
Anaemia with macrocytosis and polychromasia
Bone Marrow
• Hypercellular marrow with normoblastic erythroid hyperplasia
• Some dyserythropoiesis is seen.
• Iron stores are decreased.
• Intermittent clinical haemoglobinuria (acute haemolytic episodes which occur mostly
at night and are identified by passage of brown coloured urine in the morning).
• Haemosiderinuria and venous thrombosis are common.
Sucrose Haemolysis Test
A screening test for PNH, it is more sensitive than Hams test given below, though lacks
specificity. Sucrose enhances complement binding to RBCs and haemolysis is by classic
pathway of complement. Sucrose lysis test is done to find out degree of haemolysis
(. 10% haemolysis is diagnostic of PNH).
Hams Test (for Definitive Diagnosis of PNH)
The patient’s cells undergo haemolysis (by alternative complement pathway) in compatible
acidified serum at 37°C. The serum may be the patient’s own or from another normal
subject. Ten to fifty percent lysis indicates a positive test.

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