Download - Thrombocytosis uniba 16-1-13

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Thrombocytosis

dr Putra Hendra SpPD

UNIBA

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PlateletαGranule :Glycoprotein

Thrombospondin VEGF

PDGF

Angiogenesis

Dense granule : Ca Serotonin ADP Thromboxane A2

Aggregation

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Platelet aggregation

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Definition of Thrombocytosis

Platelet count > 450,000/ml

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Three Major Causes ..…

… Familial thrombocytosis… Clonal thrombocytosis… Reactive thrombocytosis

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Familial Thrombocytosis…

Rare case reports…Hereditary……mutation of TPO gene…mutation of c-mpl receptor Overproduction of thrombopoitein

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Clonal Thrombocytosis

… Essential thrombocythemia… Polycythemia Vera… Chronic Myelocytic Leukemia… Myelofibrosis with Myeloid Metaplasia

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

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How to differentiate ?

Clonal …myeloproliferative…dysregulation…malignant changes

…thrombotic/hemo-rrhagic complication

Reactive …secondary

responses…physiological

feedback…transient and

subsides…exceedingly rare/ Kawasaki disease

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Clonal

mpl

TPO

Sensitivity to TPO

Reactive

TPO

IL-6

IL-3

IL-11

GM-CSF

EPO

P P

MegaMega

Proliferation Proliferation

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Diagnosis…Clonal thrombocythemia … Blood Smear …Myelocyte …Metamyelocyte …Thrombocyte

… Bone Marrow aspirate/biopsy …Giant megakaryocyte … Hypercellularity … Hyperplasia

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Diagnosis …Clonal thrombocythemia

… Cytogenetic study

CML,Ph1,bcr-abl

… Platelet aggregation test

ADP,Epinephrine

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ET - Symptoms

• Many patients are asymptomatic at time of diagnosis

• Digital ischemia from microvascular thrombi

• Erythromelalgia• Pruritis• Hemorrhage - seen in 40% of pts

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Complication…Clonal thrombocytemia…Neurologic: …Headache …TIA

…Thrombosis: …Coronary …Renal …Portal …DVT, Pul

…Bleeding: …GI …Skin …Eye …Brain …Urinary tract

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…Pregnancy: …Spontaneous abortion

…IUGR

…Others: …Erythromelalgia

… Digital gangrence

Complication…Clonal thrombocytemia

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Diagnosis …Reactive Thrombocytosis

…Rountine blood count…History

( URI,IDA,Surgery,Hemorrhage,Malignancy )…Elevated IL,APP,GM-CSF …ANA,RA…Anemia workup…Tumor marker

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Complication …Reactive thrombocytosis …Underlying disease …Kawasaki disease: at risk of coronary

thrombosis or rupture

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TreatmentClonal…Hydroxyurea…Anagrelide…IFNα…Phosphorus-32…Low dose Aspirin…

…BMT

Reactive…Treat underlying…No need unless

platelet >1,000,000…Aspirin for Kawasaki

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Cortelazzo S et al. N Engl J Med 1995;332:1132-1137

Mean ({+/-}SD) Platelet Counts of 114 Patients with Essential Thrombocythemia Treated with Hydroxyurea or Left Untreated

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Cortelazzo S et al. N Engl J Med 1995;332:1132-1137

Probability of Thrombosis-free Survival in 114 Patients with Essential Thrombocythemia Treated with Hydroxyurea or Left Untreated

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ET - natural history

• Rarely progresses to AML (progression in <1% of pts)

• May progress to myelofibrosis• Major complication is thrombosis

– Occurs in 20-30% of patients– Clots may be arterial or venous