Aspirin cures erythromelalgia and cerebrovascular disturbances in JAK2-thrombocythemia through platelet-cycloxygenase inhibition

Figure 14 Vaso-active substances, prostaglandins endoperoxides and other factors released during JAK2 mutated platelet aggregation account for the inflammatory symptoms in JAK2-thrombocythemia of ET and PV patients. Upper part: Simultaneous study of clinical signs and symptoms of erythromelalgia, platelet activation markers and increased urinary thromboxane B2 (TxB2) excretion (right) in three ET patients during attacks of erythromelalgia after discontinuation of aspirin. This was associated with large amounts of urinary thromboxane B2 (TxB2) excretion (right) and high levels of beta-thromboglobulin (middle) at time of aspirin responsive erythromelalgic symptoms in JAK2 thrombocythemia. Erythromelalgia was successfully treated with a platelet-specific aspirin regimen of 50 mg per day, which was associated with correction of beta-TG to normal (right) and correction of TxB2 urinary excretion to normal (right). Treatment with 100 mg aspirin per day did even further decrease platelet activation markers beta-TG and TxB2 urinary excretion reaching completely normal levels[80]. Lower part: The effects of intervention with aspirin on platelet factor 4 (PF4) and bete-thromboglobulin (beta-TG) in 20 controls, 16 cases of thrombocythemia without erythromelalgia (E-), in 5 cases of thrombocythemia complicated by erythromelalgia (E+) and no aspirin, and in 5 cases after curative treatment of erythromelalgia in thrombocythemia patients (E+ → E-left and middle)[66,67]. Decreased platelet 5-HT and increased beta-TG and PF-4 during a documented migraine attack (grey zone) demonstrating that in such patients migraine is a platelet disorder with documented in vivo platelet activation during the attack[53,62,64,67]. ^aP < 0.05 vs control.