Thrombocytosis

Presented by Ri
Platelet
Granule :
Glycoprotein
Thrombospondin
VEGF
PDGF

Angiogenesis
Dense granule :
Ca
Serotonin
ADP
Thromboxane A2

Aggregation
Platelet aggregation
Definition of Thrombocytosis



Platelet count > 450,000/ml
Three Major Causes ..
Familial thrombocytosis
Clonal thrombocytosis
Reactive thrombocytosis
Familial Thrombocytosis
Rare case reports
Hereditary
mutation of TPO gene
mutation of c-mpl receptor
Overproduction of thrombopoitein
Clonal Thrombocytosis
Essential thrombocythemia
Polycythemia Vera
Chronic Myelocytic Leukemia
Myelofibrosis with Myeloid Metaplasia

Reactive Thrombocytosis
Infection
Malignancy
Autoimmune diseases
Postsplenectomy
Trauma
Rebound thrombocytosis
Anemia
Hemorrhage Drug(Vincristine,steroid), etc

How to differentiate ?
Clonal
myeloproliferative
dysregulation
malignant changes
thrombotic/hemo-rrhagic
complication

Reactive
secondary responses
physiological feedback
transient and subsides
exceedingly rare/
Kawasaki disease
Clonal

mpl



TPO




Sensitivity
to TPO







Reactive

TPO
IL-6

IL-3
IL-11
GM-CSF
EPO
P P
Mega
Mega
Proliferation
Proliferation
DiagnosisClonal thrombocythemia
Blood Smear
Myelocyte
Metamyelocyte
Thrombocyte


Bone Marrow aspirate/biopsy
Giant megakaryocyte
Hypercellularity
Hyperplasia


Diagnosis Clonal thrombocythemia
Cytogenetic study
CML,Ph1,bcr-abl


Platelet aggregation test
ADP,Epinephrine

ComplicationClonal thrombocytemia

Neurologic:
Headache
TIA
Thrombosis:
Coronary
Renal
Portal
DVT, Pul
Bleeding:
GI
Skin
Eye
Brain
Urinary tract


Pregnancy:
Spontaneous abortion
IUGR


Others:
Erythromelalgia
Digital gangrence
ComplicationClonal thrombocytemia
Diagnosis Reactive Thrombocytosis
Rountine blood count
History ( URI,IDA,Surgery,Hemorrhage,Malignancy )
Elevated IL,APP,GM-CSF
ANA,RA
Anemia workup
Tumor marker
Complication Reactive thrombocytosis
Underlying disease
Kawasaki disease: at risk of coronary thrombosis or rupture

Treatment
Clonal
Hydroxyurea
Anagrelide
IFN
Phosphorus-32
Low dose Aspirin


BMT
Reactive
Treat underlying
No need unless platelet
>1,000,000
Aspirin for Kawasaki


Thrombocytosis
good or not good ?
Thrombocytosis and cancer
Billroth :existence of cancer cells in association with
thrombus
Almost every step of the metastatic process linked to
platelet involvement
Association of thrombocytosis and poor prognosis in
stomach, colon, lung, kidney, and prostate cancer
Limitation :negative association is rarely published


The Lancet Oncology, Volume3 Number 7 (July 2002)

Figure 4. Schematic diagram of a circulating tumor cell (blue) adhering to the vascular endothelium (red)
with the assistance of platelets (yellow) in a small vessel. Activated platelets swell and adhere to tumor
and endothelial cells via integrins. After attachment of the tumor cell to the endothelium, retraction of
endothelial cells allows the tumor cell to move out of the vessel (extravasation).

Thrombocytosis in intensive care
A retrospective study
At least one platelet count > 450,000 (21.7% of patients)
lower ICU mortality (p=0.003)
lower hospital mortality (p=0.006)
longer duration of ICU stay (p=0.0001)
Thrombocytosis, an independent predictor of favorable
outcome
Limitation :retrospective study, time course, trauma
hospital
British Journal of Anaesthesia, 87(6):926-8 (2001)

Time course of platelet count in ICU
The prognostic value of a single platelet count is of little value and
maybe misleading
Late thrombocytopenia is more predictive of death than early
thrombocytopenia
A relative increase in platelet count after thrombocytopenia was
present only in survivors





Critical Care Medicine Volume 30 Number 4 (April 2002)




Figure 3. Daily platelet count in the 189 intensive care unit (ICU)
survivors (unfilled circles) and the 68 nonsurvivors (filled circles)
who stayed for at least 14 days in the ICU.





Does FOY (Gabaxate) induce thrombocytosis ?
Does FOY (Gabaxate) induce thrombocytosis ?
A case report
46 y/o woman, hemorrhagic tendency, ITP diagnosed
Foy (2000mg/day) for 4 days to prevent DIC
Platelet count:
Before treatment: 15,000
Day 4: 250,000
Day 7:28,000 due to discontinue
2nd FOY administration, transient increase again


Japanese Journal of Clinical Hematology


FOY and ITP
Another case report
47 y/o woman, subcutaneous hemorrhage, hematemesis,
platelet: 1,000, ITP diagonosed
FOY (1500mg/day) infusion
platelet: 85,000, hematemesis disappeared
Discontinue, platelet: 1,000
The complement inhibitory action of Gabaxate might have
contribute to platelet increase
Thank you for your attention !!
References
Thrombocytosis and thrombocythemia, Blood reviews(2001)15,159-166 A.I.Schafer
Sticky platelet syndrome and thrombocythemia, Hematology/oncology Clinics of North
America, Volume 17 Number 1 (February 2003) Eugene P.Frenkel, Eberhard F.Mammen
Platelets and cancer, The Lancet Oncology, Volume3 Number 7 (July 2002) GF Nask et al
Thrombocytosis in intensive care, British Journal of Anaesthesia, 87(6):926-8 (2001)
A.M.Gurung et al
Time course of platelet counts in critical ill patients, Critical Care Medicine Volume 30
Number 4 (April 2002) Sendar Akca et al
Gabaxate mesilate induced recovery from the thrombocytopenia in a patient with acute
ITP, Japanese Journal of Clinical Hematology, 37(7):624-9 (1996 Jul) Toyozumi H &
Ikeda Y.
Gabaxate mesilate induced remarkable transient reversal of thrombocytopenia in a ITP
patient, Japanese Journal of Clinical Hematology, 32(3):227-30 (1991 Mar) Hashimoto M.
et al