Page 133 - Essential Haematology

Chapter 8 White cells: Granulocytes and monocytes / 119

Benign e thnic n eutropenia antibody may be directed against one of the
neutrophil - specific antigens (e.g. NA, NB).

It has been known for many decades that black
people often have a low neutrophil count. It is now
clear that up to 98% of people of West African Idiopathic b enign n eutropenia
origin carry a polymorphism in the Duff y antigen
chemokine receptor (DARC) gene which leads to An increase in the marginating fraction of blood
loss of DARC expression on red cells. Th is has neutrophils and a corresponding reduction in the
apparently been selected during evolution because circulating fraction is one cause of benign neutro-
the malaria parasite Plasmodium vivax uses DARC penia. Th is may in some races be related to reduced
as a receptor to enter the red cell. DARC is a chemo- DARC expression as discussed above. Many healthy
kine receptor and the loss of red cell DARC expres- Africans and other races, especially in the Middle
sion leads directly to the clinical state of benign East, have a low peripheral blood neutrophil count
ethnic neutropenia. Th e effect is to lower the median without excess margination. Th ese subjects have no

neutrophil count by around 0.5 × 10 /L in this increased susceptibility to infection and the bone
9
population. There does not appear to be any signifi - marrow appears normal although there is dimin-

cant clinical sequelae and the reduced blood cell ished neutrophil production.
count may result from an altered pattern of neu- Finally, the term chronic idiopathic neutropenia
trophil margination. A similar effect is also seen in is used for unexplained acquired neutropenia (neu-

other populations, most notably in the Middle East. trophil count below normal for the ethnic group),

without phasic variations or underlying disease. It
is more common in females and thought to be
Congenital n eutropenia
brought about by immune cells causing inhibition
Kostmann s syndrome is an autosomal recessive of myelopoiesis in the bone marrow.
’
disease presenting in the first year of life with life -

threatening infections. Most cases are caused by

mutations of the gene coding for neutrophil elastase. Clinical f eatures
G - CSF produces a clinical response although
Severe neutropenia is particularly associated with

marrow fibrosis and acute myeloid leukaemia may
infections of the mouth and throat. Painful and
supervene.
often intractable ulceration may occur at these sites
(Fig. 8.10 ), on the skin or at the anus. Septicaemia
Drug - i nduced n eutropenia rapidly supervenes. Organisms carried as commen-

sals by healthy individuals, such as Staphylococcus
A large number of drugs have been implicated
epidermidis or Gram - negative organisms in the
(Table 8.4 ) and may induce neutropenia either by
bowel, may become pathogens. Other features of
direct toxicity or immune - mediated damage.
infections associated with severe neutropenia are
described on p. 169 .
Cyclical n eutropenia

This is a rare syndrome with 3 - to 4 - week periodic- Diagnosis
ity. Severe but temporary neutropenia occurs.
Monocytes tend to rise as the neutrophils fall. Bone marrow examination is useful in determining
Mutation of the gene for neutrophil elastase under- the level of damage in granulopoiesis (i.e. whether
lies some cases. there is reduction in early precursors or whether
there is reduction only of circulating and marrow
neutrophils with late precursors remaining in the
Autoimmune n eutropenia
marrow). Marrow aspiration and trephine biopsy
In some cases of chronic neutropenia an autoim- may also provide evidence of leukaemia, myelodys-
mune mechanism can be demonstrated. Th e plasia or other infi ltration.