March/April - West Virginia State Medical Association

Scientific Article |
Unique Association of Myeloid Neoplasm with
Eosinophilia and Abnormalities of PDGFRA with TTP
Lubna N. Chaudhary, MD
PGY-II Internal Medicine Resident, WVU, Morgantown
Nathanael G. Bailey, MD
Department of Pathology, WVU, Morgantown
Jeffrey A. Vos, MD
Department of Pathology, WVU, Morgantown
Christy J. Stotler, DO
Division of Hematology & Oncology, Mary Babb
Randolph Cancer Center, WVU, Morgantown
Corresponding Author: Lubna N. Chaudhary, MD, Dept.
of Internal Medicine, West Virginia University, Morgantown,
WV 26506. lchaudhary@hsc.wvu.edu
Abstract
Myeloid neoplasm with eosinophilia
and abnormalities of Alpha type platelet
derived growth factor receptor (PDGFRA)
is a type of hypereosinophilic syndrome
characterized by multiorgan damage due
to eosinophilia. Its association with
thrombotic thrombocytopenic purpura
(TTP) has rarely been reported. We
describe here a case report of a female in
whom TTP presented as one of the earlier
manifestations of myeloproliferative HES
with rearrangement of PDGFRA. Our
patient was found to have a normal
ADAMTS-13 level which is not commonly
seen with TTP. This case illustrates the
importance of recognizing the atypical
presentations of HES which may be
difficult to recognize.
Introduction
The hypereosinophilic syndromes
(HES) are a group of disorders
characterized by sustained
overproduction of eosinophils,
in which eosinophilic infiltration
and mediator release cause
damage to multiple organs, most
commonly heart, lung, central
nervous system, gastrointestinal
tract and skin. The evaluation
of HES is extensive and requires
investigation of all underlying
reactive and neoplastic etiologies
of eosinophilia. The diagnosis
of idiopathic hypereosinophilic
syndrome, therefore, is one
of exclusion. The idiopathic
hypereosinophilic syndrome was
first defined by Chusid et al in 1975
as (1) persistent eosinophilia of
1.5x10 9/L or more for longer than
6 months associated with signs and
symptoms of hypereosinophilic
disease; (2) a lack of evidence for
parasites, allergies or other known
causes of eosinophilia; and (3)
presumptive signs and symptoms
of organ involvement. 1 The most
common mutation associated with
the myeloproliferative variant of
HES is the fusion tyrosine kinase
FIP1L1/PDGFRA. Patients with this
mutation respond dramatically to the
tyrosine kinase inhibitor, imatinib
mesylate, with clinical, hematological
and molecular remission.
Thrombotic thrombocytopenic
purpura (TTP) is a life threatening
disorder characterized by
thrombocytopenia, microangiopathic
hemolytic anemia (MAHA) and
less consistently with fever, renal
involvement and neurological
symptoms. Recent studies have
indicated that the deficiency of A
Disintegrin-like and Metalloprotease
with Thrombospondin Type
1 Motif, 13 (ADAMTS13) is a
cause of TTP. 2,3 ADAMTS13 is a
von Willebrand factor-cleaving
protease and its deficiency causes
accumulation of ultra-large
multimers of VWF responsible
for the thrombotic and MAHA
complications of this disease. HES
and thrombotic thrombocytopenic
Abbreviations Used Explanation
FIP1L1-PDGFRA FIP1-like 1-Platelet derived growth factor receptor type A
TTP
Thrombotic Thrombocytopenic purpura
HES
Hypereosinophilic syndrome
ADAMTS-13 A Disintegrin-like and Metalloprotease with Thrombospondin Type 1 Motif, 13
MAHA
Microangiopathic hemolytic anemia
VWF
Von Williebrand factor
LDH
Lactate dehydrogenase
PEX
Plasma exchange
FISH
Florescent in-situ hybridization
CHIC2 Cysteine-rich hydrophobic domain 2
RT-PCR
Reverse transcriptase-polymerase chain reaction
ADCC
Antibody dependent cell-mediated cytotoxicity
6 West Virginia Medical Journal