Page 330 - Textbook of Pathology, 6th Edition

314 ii) Pancytopenia (mild granulocytopenia and thrombo-
cytopenia frequent).
iii) Intermittent clinical haemoglobinuria; acute haemo-
lytic episodes occur at night identified by passage of
brown urine in the morning.
iv) Haemosiderinuria very common.
v) Venous thrombosis as a common complication.
The presence of inordinate sensitivity of red blood cells,
leucocytes and platelets to complement in PNH can be
demonstrated in vitro by Ham’s test using red cell lysis at
acidic pH or by sucrose haemolysis test.
About 20% cases of PNH may develop myeloproli-
ferative or myelodysplastic disorder and some even
develop acute myeloid leukaemia.

E. HAEMOLYTIC ANAEMIA IN SPLENOMEGALY
Haemolytic anaemia is common in splenic enlargement from
SECTION II
Figure 12.22 Malarial parasite, Plasmodium falciparum, in the any cause (Chapter 14). Normally, the spleen acts as a filter
peripheral blood showing numerous ring stages and a crescent of and traps the damaged red blood cells, destroys them and
gametocyte. The background shows a normoblast. the splenic macrophages phagocytose the damaged red cells.
A normal spleen poses no risk to normal red blood cells. But
4. Other microorganisms such as pneumococci, staphylococci splenomegaly exaggerates the damaging effect to which the
and Escherichia coli. red cells are exposed. Besides haemolytic anaemia,
5. Copper by direct haemolytic effect on red cells in Wilson’s splenomegaly is usually associated with pancytopenia.
disease and patients on haemodialysis. Splenectomy or reduction in size of spleen by appropriate
6. Lead poisoning shows basophilic stippling of red blood therapy relieves the anaemia as well as improves the
cells. leucocyte and platelet counts.
7. Snake and spider bites cause haemolysis by their venoms.
8. Extensive burns. II. HEREDITARY (INTRACORPUSCULAR)
HAEMOLYTIC ANAEMIA
D. PAROXYSMAL NOCTURNAL
HAEMOGLOBINURIA (PNH) Hereditary haemolytic anaemias are usually the result of
intracorpuscular defects. Accordingly, they are broadly
PNH is a rare acquired disorder of red cell membrane in classified into 2 groups (see Table 12.9):
which there is chronic intravascular haemolysis due to undue Hereditary abnormalities of red cell membrane.
sensitivity of red blood cells to complement due to defective Hereditary disorders of the interior of the red cells.
synthesis of a red cell membrane protein. The defect affects
all the cells of myeloid progenitor lineage (RBCs, WBCs, A. HEREDITARY ABNORMALITIES OF
platelets) suggesting a deficient haematopoiesis. The disorder RED CELL MEMBRANE
generally presents in adult life.
The abnormalities of red cell membrane are readily identified
Haematology and Lymphoreticular Tissues
PATHOGENESIS. PNH is considered as an acquired clonal on blood film examination. There are 3 important types of
disease of the cell membrane while normal clone also inherited red cell membrane defects: hereditary
continues to proliferate. The defect is a mutation in the stem spherocytosis, hereditary elliptocytosis (hereditary
cells affecting myeloid progenitor cells that is normally ovalocytosis) and hereditary stomatocytosis.
required for the biosynthesis of glycosyl phosphatidyl
inositol (GPI) essential for anchoring of the cell; the mutant Hereditary Spherocytosis
form of the gene is an X-linked gene called PIG-A
(phosphatidyl inositol glycan). Thus, as a result of mutation, Hereditary spherocytosis is a common type of hereditary
there is partial or complete deficiency of anchor protein. Out haemolytic anaemia of autosomal dominant inheritance in
of about 20 such proteins described so far, the lack of two of which the red cell membrane is abnormal.
the proteins—decay accelerating factor (DAF, CD55) and a PATHOGENESIS. The molecular abnormality in hereditary
membrane inhibitor of reactive lysis (MIRL, CD59), makes the spherocytosis is a defect in proteins which anchor the lipid
RBCs unduly sensitive to the lytic effect of complement. bilayer to the underlying cytoskeleton. These protein
abnormalities are as under and are schematically illustrated
CLINICAL AND LABORATORY FINDINGS. Clinical in Fig.12.23:
and laboratory findings are as under: 1. Spectrin deficiency. Almost all cases have deficiency in
i) Haemolytic anaemia. the structural protein of the red cell membrane, spectrin.