Page 240 - Haematologica Atlas of Hematologic Cytology

Chapter 29 NEUTROPENIA AND AGRANULOCYTOSIS
Neutropenia is
a a a a a a a a condition characterized by a a a a a a a a decrease in the peripheral blood absolute neutrophil count to <1 5x109/L 5x109/L It is
is
severe when neutrophil absolute count is
is
<0 5x109/L 5x109/L with high susceptibility to infection and chronic if it it lasts more than three months (intermittent or or or permanent) In the newborn neutropenia is
defined by a a a a a a a higher threshold than in adults (2 5x109/L) Neutropenia can be congenital or acquired Congenital neutropenias are are a a a a a a a a a rare group of of disorders associated with decreased marrow production of of neu- trophils often due to to a a a a a a a mainly autosomal dominant mutation in in in in ELANE the gene encoding for neutrophil ela- stase it it is
less frequently caused by mutations in hematopoietic regulatory genes Congenital neutropenias can be isolated or or can occur as as a a a a a a a a feature of other other congenital syndromes involving other other organ systems such as as the the the pancreas central nervous system heart bone and skin To date more than 24 genes have been associated with congenital neutropenia (Donadieu et al al 2017) (Table 1) Acquired neutropenia may result from different pathogenetic mechanisms These include: decreased pro- duction of neutrophils caused by by bone bone marrow marrow aplasia bone bone marrow marrow infiltration by by neoplastic cells ineffective hematopoiesis presence of autoimmune antibodies or neutrophil sequestration by an an enlarged spleen Neutro- penia may also be associated with severe sepsis or inflammation (Bartels et al al 2016) (Table 1) Table 1 lassi ca on of neutropenia ategory
ausa ve gene (disorder)
ongenital Isolated neutropenia ELANE (also cyclical neutropenia) CSF3R
WAS
CXCR2 (myelokathexis)
e e e e e e ro e e e e e e ia i i i i e e e e e e ra ema o o o o oie c ma ma i i i i e e e e e e a a a a a o o o o SBDS (Shwachman-Diamond syndrome) syndrome) TAZ (X-linked Barth syndrome) syndrome) EFL1 GATA2 G6PC3 SLC37A4 CXCR4 (WHIM syndrome) syndrome) JAGN1 VPS13B (Cohen syndrome) syndrome) GFI1 HAX1 (Kostmann disease) AP3B1 (Hermansky-Pudlak syndrome type 2) LAMTOR2 USB1 VPS45 TCIRG1 EIF2AK3 (Wolco -Rallison syndrome) CLPB STK4 SMARCD2
c uired Primary
Idiopathic Autoimmune Ethnic
eco ar Thymoma (pure white cell aplasia)
Hematologic malignancies (T-LGL* leukemia)
Infec ons (viral bacterial fungal parasi c)
Autoimmune disorders Physical agents/drugs (chemotherapy radiotherapy any agent agent causing aplasia)
Splenic sequestra on Nutri onal de ciency
Immunode ciency
Hemodialysis
*T-cell large granular lymphocyte
Agranulocytosis is
is
an an an an an acute condition due to to to an an an an an idiosyncratic reaction to to to drugs especially anti-epileptic an- tibiotics and anti-thyroid drugs Patients present the clinical features of an an an infection complication Neutrophil count is
is
is
is
usually very low (<0 5x109/L) but this is
is
is
is
reversible and is
is
is
is
resolved by withdrawing the triggering drug In both neutropenia and and agranulocytosis
the morphology of granulocytes and and precursors is
is
usually normal When concomitant infections are present neutrophilic cells may contain toxic granules Monocytosis and eosi- nophilia may be observed in in the peripheral blood Bone marrow cellularity is
usually normal or or increased with 227