Essential thrombocytosis

Today we discussed essential thrombocytosis (AKA essential thrombocythemia). Some points about this condition:

Thrombocytosis
Majority of cases are reactive. Common causes: Post-op, infection, post-splenectomy, Fe deficiency, malignancy (non-hematologic)

Non-reactive causes include ET, polycythemia vera, myelofibrosis, CML, MDS

ET:
Concerns are
1)Thrombosis risk
2)Bleeding risk (platelets are numerous, but often dysfunctional, and patients can have acquired von willebrand's disease)
3)Potential for transformation to AML

Epidemiology:
median age at dx is 60. F:M is 2:1.
Clinical: ~1/3 asymptomatic. ~1/3 have "vasomotor" sx: Syncope/presyncope, H/A, paresthesias, visual dist, non-exertional c/p. ~1/3 have sx consistent with thrombotic/bleeding events- major or minor

Diagnosis:
PLT consistently above 600, no explanation for reactive cause. May see megakaryocyte hyperplasia on BMBx if done, -ve BCR-ABL, iron replete, no evidence of MDS. JAK2 is a mutation found in over 95% of patients with polycythemia rubra vera, and 50-60% of patients with ET. It can be detected in peripheral blood

Bleeding risk
This paper by Tefferi et al from the Mayo Clinic found a 4% 10-year risk of major hemorrhage. Bleeding risk was directly proportional to PLT level, with over 1500 (i.e. 1.5 million) highest.

Thrombosis Risk
Arterial and venous thrombosis may occur. Typical events are similar to those in PRV: stroke, TIA, ACS, retinal art occ, digital ischemia, pregnancy loss. Less commonly, DVT/PE, PV thromb/Budd-Chiari.
Incidence of major events (MI, stroke, PE) is ~4% at 10 years. There is conflicting data on whether PLT level correlates with thrombosis risk

Antiplatelet therapy
The ECLAP study (RCT) looked at low dose ASA in patients with no other indication for ASA and PRV (which carries similar thrombosis risk)
RR of composite outcome of MI, stroke, PE, CV death was 0.4 on ASA 100mg. No significant mortality benefit. No significant difference in bleeding. It also has demonstrated effect on vasomotor sx of ET.

Cytoreductive therapy in high risk pts
In those meeting high risk criteria (i.e. over 60 or history of thrombosis). this RCT by Cortelazzo et al, evaluated the use of hydroxyurea to bring PLT count to below 600 vs. placebo in patients on antiplatelet therapy. 2 year risk of significant thrombosis was 3.6% on HU, 24% on placebo (NNT 5) Therefore, hydroxyurea to reduce the platelet count to below 600 should be considered in high risk patients. Specific platelet reducing agent (Anagrelide) was evaluated in RCT vs. HU, and showed much higher thrombosis risk



The risk of conversion to AML is reported at 2-5% at 15 years from dx. This is the lowest risk of any of the myeloproliferative disorders