Thrombocytosis
GENERAL PRINCIPLES
Definition
Thrombocytosis is defined as a platelet count of gt;450 ? 109#8725;L by the World Health Organization (WHO).
Etiology
Thrombocytosis has reactive and clonal etiologies that may coexist.
• Reactive thrombocytosis may occur during recovery from thrombocytopenia; after splenectomy; or in response to iron deficiency, acute infectious or chronic inflammatory states, trauma, and malignancies.
î Low risks of thrombosis or bleeding.
î Platelets normalize after improvement of the underlying disorder.
î If accompanied by thrombotic complications, evaluate for an underlying myeloproliferative disorder.
DIAGNOSIS
Clinical Presentation
HISTORY
ET may present as an incidental discovery or present with thrombotic or hemorrhagic symptoms. The risk of thrombosis increases with age, prior thrombosis, duration of disease, and other comorbidities. Erythromelalgia, due to microvascular occlusive platelet thrombi, presents as intense burning or throbbing of the extremities, typically involving the feet. Cold exposure usually relieves symptoms. Hemorrhage can occur with platelet counts gt;1000 ? 109#8725;L due to acquired deficiencies of large vWF multimers.29
PHYSICAL EXAMINATION
Approximately 50% of ET patients develop mild splenomegaly. Typical signs of erythromelalgia include erythema and warmth of affected digits.
Diagnostic Criteria
The 2016 WHO revised criteria (requires all four) include30:
• Platelet count #8805; 450 ? 109#8725;L.
• Bone marrow biopsy showing increased mature megakaryocytes and no increase in erythropoiesis or granulopoiesis or reticulin fiber deposition greater than grade I.
• Exclusion of BCR-ABL1 positive chronic myelogenous leukemia (CML), polycythemia vera, primary myelofibrosis, myelodysplastic syndrome, or other myeloid neoplasm.
• Presence of JAK2 V617F, CALR, or MPL mutation or, if clonal marker not present, no evidence for reactive thrombocytosis.
TREATMENT
• Patients with high or intermediate risk of thrombosis based on the International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET)31 (high: age gt; 60 years with a JAK2 V617F mutation and#8725;or a history of thrombosis at any age, intermediate: age gt; 60, no JAK2 mutation, no history of thrombosis) require cytoreduction therapy.
î Platelet-lowering drugs include hydroxyurea and anagrelide or interferon-#945; in pregnant patients or females in their childbearing years. The majority of thrombotic complications occur at modest platelet count elevations.
î Hydroxyurea is superior that anagrelide to prevent thrombotic and hemorrhagic complications in the randomized controlled trial, so hydroxyurea and aspirin (ASA) is the standard first line therapy for patients with ET at high risk for vascular events.32
î Treatment typically aims for a platelet count of #8804;400 ? 109#8725;L.
• Patients age 60 or younger and no history of thrombosis can be managed without cytoreductive therapy;
they are treated with aspirin or observation alone.
• Plateletpheresis rapidly lowers platelet counts, although it is reserved for patients who have acute arterial thromboses.