High platelet levels do not necessarily signal any clinical problems, and are picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory disease, as the principal stimulants of platelet production (e.g. thrombopoietin) are elevated in these clinical states as part of the acute phase reaction.

A very small segment of patients report symptoms of erythromelalgia, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin use.

Vasomotor symptoms including headache, change in vision, lightheadedness, acral dysethesia, and atypical chest pain are more common in autonomous thrombocytosis but can certainly be seen in reactive thrombocytosis and are amenable to aspirin therapy. The rates of thrombosis and/or hemorrhage are higher in autonomous (24%) vs. reactive (1-3%) extreme thrombocytosis.