V 20TH ANNIVERSARY
2 February 1999
CE Refereed Peer Review
FOCAL POINT
★The diagnosis of essential
thrombocythemia (ET) must
be made by ruling out other
myeloproliferative disorders
and more common causes of
an elevated platelet count, such
as inflammatory disease or
infection.
KEY FACTS
■ Diagnostic criteria developed in
the field of human oncology are
the best guidelines with which
to establish a diagnosis of ET in
dogs and cats.
■ Reactive causes of
thrombocytosis are considerably
more common than are
myeloproliferative causes and
should therefore be aggressively
ruled out before considering a
diagnosis of ET.
■ The presence of megakaryocytic
hyperplasia on bone marrow
cytology or histopathology is
recommended as an additional
diagnostic criterion by many
oncologists treating human
patients with ET.
■ Other significant supportive
criteria for diagnosis include
splenomegaly, abnormal platelet
or megakaryocyte morphology,
and platelet dysfunction.
Vol. 21, No.
Essential
Thrombocythemia in
Dogs and Cats. Part I.
Auburn University
Alexandra Chisholm-Chait, VMD
ABSTRACT: Essential thrombocythemia is a rare type of myeloproliferative disorder that must
be differentiated from other causes of excessive circulating platelets. In cases of essential
thrombocythemia, the elevated platelet count is caused by clonal expansion of megakaryocyte
precursors; in addition, platelets and megakaryocytes are often morphologically and function-
ally abnormal. This article reviews several distinguishing features and the terminology used to
describe myeloproliferative disorders and other causes of thrombocytosis, with respect to dif-
ferentiating between these diseases.
E
ssential, or primary, thrombocythemia (ET) is an uncommon chronic
myeloproliferative disease (MPD) typically characterized by excessive gen-
eration of morphologically and functionally abnormal platelets and/or
megakaryocytes (MKs). This augmented platelet production is derived from
clonal expansion of megakaryocytic precursors in the bone marrow (Figure 1).1,2
Hematopoietic progenitors of the platelet lineage (and other lineages as well)
may undergo clonal amplification when genetic mutations render them more
sensitive to stimulatory cytokines or less sensitive to inhibitory cytokines that
regulate thrombopoiesis (see Cytokines that Play a Role in the Regulation of
Thrombopoiesis).3–6
Essential thrombocythemia must be distinguished from other causes of exces-
sive circulating platelets because overexuberant platelet release is more common-
ly a nonpathologic secondary reaction to overall bone marrow stimulation, as
might be expected during rebound hematopoiesis following chemotherapy. This
type of thrombocytosis results from cytokine-induced hematopoiesis and typi-
cally does not require specific treatment. Conversely, myeloproliferative causes of
augmented platelet production do warrant therapy and regular monitoring. If
thrombocytosis is associated with an underlying MPD, it is helpful to determine
the primary cell type involved because some classes of MPD may be more re-
sponsive to therapy than others are. Although ET is rare in dogs and cats, multi-
ple reports in the veterinary literature document MPDs with abnormal numbers
of circulating platelets,7–20 several of which are consistent with primary thrombo-
cythemia.14–18
Part I of this two-part presentation provides a brief review of the classifications
and terminology used to describe MPDs and other causes of thrombocytosis—
which may help to clarify the distinguishing features between these diseases; di-
Compendium February 1999 20TH ANNIVERSARY Small Animal/Exotics

TABLE I
Classification of Myeloproliferative
Disorders in Dogs and Catsa
Disorder Predominant Cell Clone
Granulocytic leukemia Neutrophils
Monocytic leukemia Monocytes
Myelomonocytic leukemia Neutrophils
and monocytes
Eosinophilic leukemia Eosinophils
Basophilic leukemia Basophils
Polycythemia vera Erythrocytes
(primary erythrocytosis)
Figure 1—Committed megakaryocyte (MK ) progenitors and Erythroleukemia complex Erythroid and
progeny. Essential thrombocythemia results when one of granulocytic series
these cell types undergoes neoplastic transformation and Thrombocythemia Platelets
clonal proliferation (BFU-MK = burst-forming unit–mega-
karyocyte; CFU-MK = colony-forming unit–megakaryocyte; Megakaryocytic or Megakaryocytes and
IL = interleukin; LD-CFU-MK = light density–colony-form- megakaryoblastic leukemia megakaryoblasts
ing unit–megakaryocyte; Pro-MK-blast = promegakaryoblast). Myelofibrosis or Marrow stromal cellsb
myelosclerosis (e.g., fibroblasts)
Smoldering (aleukemic) Any aberrant clone
Cytokines that Play a Role in leukemia that is not found in
the Regulation of Thrombopoiesis circulation and does
Stimulatory Cytokines Inhibitory Cytokines not suppress normal
Granulocyte/monocyte– Transforming growth hematopoiesis
colony-stimulating factor–β a
Adapted from Evans RJ, Gorman NT: Myeloproliferative
factor Platelet-released disease in the dog and cat: Definition, aetiology, and
classification. Vet Rec 121:437–443, 1987.
Interleukin-3 glycoprotein b
Although fibroblasts may be derived from one clone, most
Interleukin-6 Platelet factor 4 studies suggest that fibroblasts involved in myelofibrosis are
Interleukin-11 Interferon-α polyclonal and produce collagen in response to stimulation
by hematopoietic clones.23
Thrombopoietin Interferon-γ
Erythropoietin
leukemias (Figure 2B) are associated with a preponder-
ance of blast forms.21 These cells may be confined to
agnosis of ET is also discussed. Part II discusses the his- the bone marrow, detectable in circulation, and/or dis-
tory, clinicopathologic findings, and treatment of ET seminated throughout the body.15
and reviews recent advances in diagnostic methods in- Although most chronic MPDs are characterized by
vestigated in human patients. the dominance of a particular cell line, such as chronic
granulocytic leukemia, peripheral blood counts often
MYELOPROLIFERATIVE DISEASES confound diagnosis because two or more cell types may
An MPD is any neoplastic disorder characterized by be excessively represented. Categories of MPDs report-
autonomous clonal expansion of nonlymphoid he- ed in small animals include PV (clonal production of
matopoietic stem cells (Table I). MPDs are classified as erythrocytes, distinct from primary erythrocytosis de-
acute or chronic myeloid leukemias (the terms acute scribed in humans), myelomonocytic leukemia (clonal
and chronic do not refer to the duration of disease but production of neutrophils and monocytes), eryth-
rather to the maturity of the autonomous clone). Chron- roleukemia complex (expansion of erythroid and gran-
ic MPDs (Figure 2A) encompass several distinct and ulocytic clones), leukemia (basophilic, granulocytic, or
overlapping clinical conditions characterized by the ex- monocytic), ET, myelofibrosis, and aplastic ane-
uberant production of more differentiated hematopoiet- mia.12,21,22 MPDs may include intermediate or mixed
ic clones, as in polycythemia vera (PV) or ET. Acute forms or may undergo transformation from one form

CYTOKINES ■ CHRONIC MPDs ■ ACUTE MPDs

Small Animal/Exotics 20TH ANNIVERSARY Compendium February 1999

Figure 2A Figure 2B
Figure 2—(A) Chronic myeloproliferative disorders: expansion of well-differentiated neoplastic clones (yellow and
green hatched cells). (B) Acute myeloproliferative disorders: clonal proliferation of blast or poorly differentiated neo-
plastic cells (solid yellow cells).

to another over time (e.g., may start out as basophilic

leukemia but transform to a less-differentiated, acute
myeloid leukemia).12 Dysplasias of stromal cells may re-
sult in myelofibrosis, although overexuberant collagen
production more often occurs secondary to stimulation
by cytokines produced by transformed hematopoietic
clones.23 Terminology often overlaps and reflects the
subtle differences in the morphology and differentia-
tion of the clonal cell. More detailed classifications in
veterinary medicine may be found elsewhere.21,24 A re-
view of the basic hierarchy of hematopoiesis is helpful
in understanding why multiple cell lines may be aber-
rant simultaneously (Figure 3).
Figure 3— Normal hematopoiesis (Ba = basophil; BFU =
The progenitor known as colony-forming unit– blast-forming unit; CFU = colony-forming unit; CSF =
GEMM (CFU–GEMM; GEMM being loosely descrip- colony-stimulating factor; E = erythrocyte; Eo = eosinophil;
tive of the cell types into which progeny cells may dif- EPO = erythropoietin; G = granulocyte; Gemm = granulo-
ferentiate [i.e., granulocyte, erythrocyte, monocyte, and cyte, erythrocyte, monocyte, megakaryocyte; GM = granulo-
megakaryocyte]) is a myeloid stem cell capable of limit- cyte monocyte; IL = interleukin; M = monocyte; Meg =
ed self-replication and differentiation into daughter megakaryocyte; TPO = thrombopoietin).
cells. These progeny and, in turn, their subsequent
progeny have progressively narrower spectrums of dif-
ferentiation potential until they are finally “unipoten- and, in fact, are not morphologically recognizable with
tial.” Unipotential cells can only differentiate into one light microscopy. For the most part, these pluripoten-
specific cell type, which we recognize on a blood smear. tial cells exist in a quiescent state and enter the cell cy-
Examples of unipotential progenitors include colony- cle only when the demand for hematopoiesis exceeds
forming unit–eosinophil (CFU-Eo), burst-forming the ability of more differentiated CFUs to supply
unit–erythrocyte (BFU-E), CFU-G, CFU-M, and CFU- cells,12 such as would be expected following total body
Meg, which respectively differentiate into eosinophils, irradiation or chemotherapy toxicosis. Which commit-
erythrocytes, neutrophils, monocytes, and MKs (then ted progeny predominates depends on the local envi-
platelets). ronment of stimulatory and inhibitory cytokines.
As expected, pluripotential stem cells represent a Why animals develop MPD remains poorly under-
much smaller proportion (less than 0.01%) of stood. There is a clear association between infection with
hematopoietic progenitors. They are much less distin- the leukemia virus and development of subsequent neo-
guishable than are their more differentiated progeny plastic and dysplastic marrow disease in cats; however, no

NORMAL HEMATOPOIESIS ■ CFU-GEMM ■ UNIPOTENTIAL PROGENITORS

 Compendium February 1999 20TH ANNIVERSARY Small Animal/Exotics

such associations have been confirmed in dogs. As MPDs

are diagnosed and characterized more fully in the pet pop- Causes of Reactive Thrombocytosis
ulation, definitive patterns of genetic or viral influence are According to Duration of
likely to emerge. At this Elevated Platelet Counta
Causes of time, diagnostic criteria de- Acute/Transient Chronic
Thrombocytosis veloped in the field of hu-
man oncology, modified to Lasting minutes to ■ Iron deficiency
Reactive thrombocytosis accommodate the different hours (chronic blood loss)
■ Infection laboratory parameters ap- ■ Epinephrine
propriate to veterinary pa- — Gastrointestinal/
■ Inflammation ■ Vincristine cutaneous
tients, are the best guidelines
■ Iron deficiency with which to categorize ■ Exercise parasitism
■ Hemorrhage MPDs in dogs and cats. — Chronic
■ Surgery Furthermore, use of these Lasting hours to days
inflammatory
■ Hyperadrenocorticism standardized guidelines ■ Acute hemorrhage
bowel disease
or exogenous should help to establish a ■ Recovery from acute
nomenclature that can be ■ Chronic inflammatory
glucocorticoids infection
used to search the current disease
■ Release from storage ■ Postthrombocytopenia
and future veterinary litera- ■ Hyperadrenocorticism
sites (splenectomy, (rebound)
ture effectively and compre- ■ Chronic infectious
lung lobectomy, hensively using narrow and — Post–immune
disease
splenic contraction) specific terms. mediated
— Toxoplasmosis
■ Nonspecific bone As MPDs become better — Postchemo-
described within the veteri- — Hepatozoonosis
marrow stimulation therapeutic
nary curriculum, we may ■ Neoplasia (may
or stimulation of other find that more astute recog- elaborate hemato-
marrow lineages nition of these conditions poietic cytokines)
(secondary results in prevalence rates ■ Hemolytic anemia
polycythemia) higher than we now appreci-
■ Splenectomy (mild
■ Metastatic carcinoma ate. More importantly, the
increasing availability of in- thrombocytosis may
house hematology equip- persist indefinitely)
Myeloproliferative
thrombocytosis ment may improve the aAdapted from Frenkel EP: The clinical spectrum of
recognition of earlier stages thrombocytosis and thrombocythemia. Am J Med Sci
■ Myelodysplasia 301(1):69–80, 1991.
of MPDs (i.e., before ani-
■ Myeloid metaplasia mals become symptomatic),
■ Polycythemia vera particularly as more veteri- describe conditions in which excessive numbers of
■ Essential narians perform bloodwork platelets are produced by dysplastic clonal MK precur-
thrombocythemia as part of routine geriatric sors. The term thrombocytosis (see Causes of Thrombo-
screens and preoperative as- cytosis) is more appropriately used to describe excessive
sessments. Preleukemic con- thrombopoiesis secondary to infection, acute or chron-
ditions may be detected by unexplained macrocytosis, nu- ic inflammation, iron deficiency, hemorrhage, surgery,
cleated erythrocytes, and large or excessively granulated and nonspecific bone marrow stimulation (i.e., reactive
platelets present in circulation.12 Once excessive or abnor- thrombocytosis [RT]).25,26
mal platelets are discovered, understanding the difference Thrombocytosis also describes the elevation in the
between thrombocytosis and ET becomes paramount. number of circulating platelets caused by sudden re-
lease from major sites of storage. Organs with extensive
MYELOPROLIFERATIVE THROMBOCYTOSIS sinusoidal blood flow (e.g., the spleen) may sequester
VERSUS REACTIVE THROMBOCYTOSIS one third or more of the body’s platelets; splenic con-
Much of the current human and veterinary literature traction induced by exercise, stress, or acute hemor-
is unfortunately peppered with inconsistent terminolo- rhage may cause a significant increase in the platelet
gy. For example, the term primary thrombocytosis is count without altering the total body platelet comple-
sometimes used instead of essential thrombocythemia to ment. RT may also occur as part of “rebound” hema-

PRELEUKEMIC CONDITIONS ■ THROMBOCYTOSIS ■ BONE MARROW STIMULATION

Small Animal/Exotics 20TH ANNIVERSARY Compendium February 1999

Figure 4—Bone marrow cytology showing a normal mega- Figure 5A

karyocyte.

topoiesis following nutritional, immune, or toxic causes

of bone marrow suppression or peripheral platelet con-
sumption.27 The duration of thrombocytosis may help
to develop a differential diagnosis list of that should be
investigated before considering the possibility of ET
(see Causes of Reactive Thrombocytosis According to
Duration of Elevated Platelet Count).
The term thrombocytosis is also used to describe condi-
tions in which the augmented platelet count occurs sec-
ondary to other MPDs or myeloid dysplasias. These con-
ditions are characterized by dysplastic hematopoietic
clones that are not of the megakaryocytic lineage but in
some way stimulate appurtenant platelet production
(i.e., myeloproliferative thrombocytosis).19 Some authors
use thrombocythemia to refer to platelet elevations associ-
ated with any MPD 27; however, the term essential throm-
bocythemia is more appropriately reserved for those
MPDs characterized by clonal expansion of a trans-
formed cell of the megakaryocytic lineage only.
The clinical syndromes of RT and ET are consider-
ably different despite the similar finding of high plate-
let counts. RT is characterized by production of func-
tionally and morphologically normal platelets and MKs
(Figure 4) and is not typically associated with an in-
creased risk of hemostatic complications.25,27 Recent
studies suggest the excessive thrombopoiesis character-
istic of RT results from the elaboration of interleukins
(IL)-1β, -4, and -6, cytokines that influence MK and
pre-MK stages of platelet production.28,29 IL-6, an acute
phase reactant released during stress or inflammation
(see Causes of Reactive Thrombocytosis According to
Duration of Elevated Platelet Count), is especially in-
fluential in the production of normal platelets in RT.29
Conversely, the hallmark of ET is abnormal platelet
and/or MK morphology30 (Figures 5A and 5B) and/or
platelet dysfunction.31–33
Figure 5B
Figure 5—(A and B) Bone marrow cytology showing
megakaryocytic dysplasia. Compared with a normal
megakaryocyte (see Figure 4), these are morphologically
abnormal with a reduced nuclear:cytoplasmic ratio and
abnormal nuclear ploidy.
Thrombopoiesis in ET occurs independent of the in-
fluences of acute phase reactants and other regulatory cy-
tokines. The role of thrombopoietin and its receptor,
however, has yet to be fully elucidated and is currently
under investigation. Buccal mucosal bleeding time and/or
assays of platelet aggregation in response to agonists such
as thrombin or platelet-activating factor are useful tests
(when available) of platelet function in cases in which an
MPD is suspected. Interestingly, the elevated platelet
count associated with ET does not always predicate a ten-
dency toward thrombosis, although thrombotic events are
common in humans, particularly within the splenic,
mesenteric, and portal vasculature.32,33 Quite the contrary,
veterinary patients with ET appear to have a greater
propensity toward excessive hemorrhage, as evidenced by
ecchymosis, petechiation, hematochezia, melena, or
hematuria.31 It should be noted that any thrombocytosis

MYELOID DYSPLASIAS ■ INTERLEUKINS ■ ACUTE PHASE REACTANTS ■ CYTOLOGY

Small Animal/Exotics 20TH ANNIVERSARY Compendium February 1999

associated with a concurrent necessary for diagnosis (see

or underlying prothrombo- Diagnostic Criteria for Essential Diagnostic Criteria for Es-
embolic condition (e.g., pan- Thrombocythemia in Humansa sential Thrombocythemia in
creatitis or hypertension) may Humans). For instance, the
augment the underlying risk ■ Platelet count in excess of 600 x 109/Lb (>700 x upper limit of a normal
of thromboembolism. 10 9/L in veterinary patients) platelet count is more vari-
Unfortunately, platelet ■ Normal erythrocyte mass/hematocrit able in veterinary patients
count and function testing ■ Stainable iron in bone marrow or failure of iron than it is in humans; platelet
alone often fail to distinguish trial (iron supplementation for 1 month does not counts in excess of 600,000/
between ET and thrombocy- µl are well documented in
result in a significant rise in hemoglobin)
tosis occurring secondary to domestic animals that are
another underlying pathology, ■ No Philadelphia chromosome or bcr/abl gene otherwise healthy. As such, a
such as infection, inflamma- rearrangementb conservative approach to in-
tion, or hemorrhage. Conse- ■ Collagen fibrosis of bone marrow absent or vestigating thrombocytosis
quently, most practitioners in <1/3 of bone marrow biopsy area is fibrosed may more appropriately be-
human oncology and some and there is no evidence of splenomegaly and gin when the platelet count
veterinary practitioners have exceeds 700,000/µl, especially
leukoerythroblastic reaction
adopted a standardized ap- when there are no other ob-
proach to the diagnosis of ET ■ No cytogenetic or morphologic evidence for a vious physical examination or
using guidelines developed by myelodysplastic syndrome clinicopathologic abnormali-
the Polycythemia Vera Study ■ No known cause for reactive thrombocytosis (no ties. Regardless of the precise
Group.34,35 These guidelines evidence of inflammation, etc.) platelet number above which
list specific clinicopathologic aRecommendations from the Polycythemia Vera Study
to consider ET, thorough ex-
features that must be present 34
Group, 1986, updated in 1997. 35 clusion of other MPDs and
or absent before attributing an b These criteria are inappropriate for veterinary patients. RT remains paramount to
elevated platelet count to ET 34,35 diagnosis.
(see Diagnostic Criteria for First, hemoglobin and
Essential Thrombocythemia erythrocyte concentrations
in Humans). must not exceed certain
Over the last two decades, thresholds because clonal ex-
those diagnostic criteria have pansion of the erythroid lin-
been modified from empha- eage is often accompanied
sizing characteristics that by secondary thrombocyto-
rule out other causes of exu- sis. PV, as discussed here,
berant platelet production represents that MPD charac-
to emphasizing the impor- terized by increased erythro-
tance of several positive cytes, platelets, and usually
markers for the disease. De- leukocytes; hepatospleno-
spite the recent prolific de- megaly; and normal to low
velopment of in vivo and erythropoietin levels. Veteri-
in vitro tests that positively Figure 6—Bone marrow histopathology showing significant nary patients with expansion
identify patients with ET, replacement of normal marrow elements with fibrosis. of only the erythroid lin-
the guidelines for diagnosis eage, no increase in platelet
have come full circle to being mostly exclusionary in or leukocyte count, and no hepatosplenomegaly may be
nature while incorporating some of these newly identi- better classified as having primary erythrocytosis (if neo-
fied positive markers as supportive criteria. plastic in origin) or secondary erythrocytosis (if it repre-
sents normal compensatory response to hypoxemia).
DIAGNOSTIC GUIDELINES Another criterion, the presence of normal iron stores in
The diagnostic guidelines developed by the Poly- bone marrow, is also necessary to rule out PV. Patients
cythemia Vera Study Group warrant further examination with PV have unregulated, overexuberant production of
because some of the criteria are not currently relevant to erythrocytes that may eventually deplete iron stores. At
the veterinary population, whereas other criteria may be some point, this reduction in available iron may serve as
better interpreted as supportive rather than absolutely “brakes” on erythropoiesis, resulting in a “falsely” normal-

POLYCYTHEMIA VERA STUDY GROUP ■ PLATELET COUNT ■ HEPATOSPLENOMEGALY

 Compendium February 1999
ENDIU
MP
20th

CO
9 - 1
9 9 9
1 9 7
ANNIVERSARY
A LookBack
The gene for thrombopoietin,
a hematopoietic cytokine
influencing the development
and maturation of cells of the
megakaryocyte lineage, was
isolated and cloned by several
independent laboratories 5 years
ago. Considerable research has
since been done to elucidate its
role in bone marrow
reconstitution following
myeloablative therapy as well as
that of it and its receptor
(c-Mpl) in the pathogenesis of
essential thrombocythemia and
other myeloproliferative
disorders. Bioassays and, more
recently, enzyme-linked
immunosorbent assays have
been developed to measure
thrombopoietin levels in
humans with platelet disorders.
As more is discovered about the
biologic characteristics of the
leukemic cell and the role of
thrombopoietin and other
cytokines in the pathogenesis of
myeloproliferative disease, gene
therapy and other more-focused
treatments may be used to
target cancer at the molecular
or genetic level. Vaccines
carrying gene vectors or tumor
antigens may soon become a
routine part of cancer therapy
for the veterinary patient.
20TH ANNIVERSARY
ized packed cell volume.
Therefore, the presence of
M’
S
normal marrow iron, or the
unveiling of overexuberant
erythrocyte production when
depleted iron stores are re-
plenished, is essential to fur-
ther exclude PV as a cause of
thrombocytosis. Further-
more, chronic hemorrhage
(as occurs with heavy parasite
burdens) and concomitant
iron deficiency may result
in RT; short of identifying
the source of blood loss, de-
pleted iron stores may be the
only evidence of chronic hem-
orrhage. Under these circum-
stances, normalization of the
platelet count following a pe-
riod of trial iron supplemen-
tation is evidence of a reac-
tive cause of thrombocytosis.
The absence of the Phil-
adelphia chromosome is a cri-
terion in humans because
those patients in whom this
chromosomal aberration is
found are predisposed to the
development of chronic mye-
logenous leukemia.35 This de-
fect results from the translo-
cation of the c-myc oncogene
to a position adjacent to an
immunoglobulin promoter
gene. The c-myc oncogene is
consequently “turned on” con-
siderably more often than it
should be, resulting in the ex-
cessive production of tran-
scriptional factors. The aug-
mented platelet count in this
disorder is thought to rep-
resent a myeloproliferative
thrombocytosis rather than a
true thrombocythemia. Al-
though chronic myelogenous
leukemia has been reported in
small animals, the technical
difficulty in karyotyping ca-
nine and feline chromosomes
precludes identification of the
Philadelphia chromosome—
CHRONIC MYELOGENOUS LEUKEMIA ■ C-MYC ONCOGENE ■ MYELOFIBROSIS
Small Animal/Exotics
and other chromosomal abnormalities—as risk factors for
particular myeloproliferative syndromes in animals. Other
gene aberrations in humans (e.g., bcr/abl rearrangement)
also increase the risk of transformation from a more differ-
entiated MPD like ET to other, prognostically more dele-
terious classes of leukemia.35,36 Again, no such genetic de-
fects have been identified in dogs or cats.
The absence of collagen in the bone marrow must be
confirmed because the process of myelofibrosis may ac-
company or result in intermittent surges in platelet produc-
tion and may also be suggestive of another underlying
MPD. If evidence of early fibrotic changes exists in the
marrow, it is important to rule out compensatory extra-
medullary hematopoiesis (which would most likely result
in splenomegaly) as a cause of thrombocytosis. It is equally
important to realize that progressive myelofibrosis (Figure
6) may occur as a late-stage sequela of many myeloprolifer-
ative diseases, including ET. Degranulation of MKs and
the subsequent elaboration of growth factors may stimulate
collagen production by adjacent marrow fibroblasts.a Conse-
quently, the presence of even a small degree of myelofibro-
sis mandates a particularly critical examination of other
marrow constituents to differentiate among possible
MPDs. Finally, any other cause of thrombocytosis (see
Causes of Thrombocytosis) must be excluded before a diag-
nosis of ET can be rendered.
Later guidelines added both positive and more specif-
ic exclusionary criteria. For example, the Rotterdam
guideline for diagnosis of ET37 includes megakaryocytic
hyperplasia and splenomegaly as additional positive cri-
teria. Furthermore, the presence of marrow osteosclero-
sis or any myelodysplastic features are considered addi-
tional exclusionary criteria for diagnosis. Undefined
clinical parameters, such as splenic enlargement, have
been refined to include more objective methods of
ascertaining spleen size using ultrasound, computed
tomography,37–39 and, more recently, nuclear scintigra-
phy.40,41 Unfortunately, the vastly heterogeneous spec-
trum of breed conformations, sizes, and weights within
our pet population precludes the development of nar-
row standardized ranges of spleen size. Nevertheless,
splenomegaly, however determined, should be consid-
ered a supportive (as opposed to an absolute) positive
criteria for diagnosis of ET.
ACKNOWLEDGMENTS
Special thanks to Clint D. Lothrop, William G.
Brewer, Jr., and Mary K. Boudreaux for providing in-
sightful comments and suggestions for this manuscript,
Joseph S. Spano for cytology slides, and Jaime Modiano
for last minute consultation.
a
Personal communication: Boudreaux M. Clinical pathology
department, Auburn University, AL, 1998.
Small Animal/Exotics 20TH ANNIVERSARY
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