Anagrelide potentially provokes acute coronary syndrome even in an adolescent affected with essential thrombocythemia concomitant with underlying persistent coronary endothelial dysfunction

Abstract

Thrombohemorrhagic disorders are the main cause of morbidities and mortalities of essential thrombocythemia (ET), which are typically observed at age 50-60 years and rarely encountered in adolescence or childhood. Recently, anagrelide, a quinazinolone derivative, has been used as a therapeutic agent for ET. Although it is used to reduce platelet count, its cardiotoxicity has been reported. Here, we present an 18-year-old boy with ET who was treated with anagrelide and developed acute myocardial infarction. This was presumed to be an effect of anagrelide administration and, specifically, damage to the coronary arterial endothelial cell exacerbated by ET.

A case of acute myocardial infarction in a patient with essential thrombocythaemia treated with anagrelide

“…It is believed to work by suppressing transcription factors involved in thrombopoiesis [ 17 ] . Anagrelide also inhibits cyclic adenosine monophosphate phosphodiesterase III pharmacologically and has inotropic and vasodilator properties; thus, the most common cardiovascular adverse events associated with anagrelide include tachycardia/palpitations [ 16 ] . Anagrelide’s impact on coronary arteries is debated, with reports of both vasospasm and vasodilation [ 16 ] .…”

“…Anagrelide also inhibits cyclic adenosine monophosphate phosphodiesterase III pharmacologically and has inotropic and vasodilator properties; thus, the most common cardiovascular adverse events associated with anagrelide include tachycardia/palpitations [ 16 ] . Anagrelide’s impact on coronary arteries is debated, with reports of both vasospasm and vasodilation [ 16 ] . Its inhibition of phosphodiesterase III is thought to cause vasodilation, but it might also increase the release of sympathetic neurotransmitters, leading to varied vascular responses [ 16 ] .…”

“…Anagrelide’s impact on coronary arteries is debated, with reports of both vasospasm and vasodilation [ 16 ] . Its inhibition of phosphodiesterase III is thought to cause vasodilation, but it might also increase the release of sympathetic neurotransmitters, leading to varied vascular responses [ 16 ] . A report by Ahluwalia et al suspected that vasoconstriction and vasodilation can occur depending on the expression patterns of alpha- and beta-adrenergic receptors in particular vessels [ 17 ] .…”

“…A report by Ahluwalia et al suspected that vasoconstriction and vasodilation can occur depending on the expression patterns of alpha- and beta-adrenergic receptors in particular vessels [ 17 ] . In addition to the long-lasting endothelial cell damage caused by ET itself, the complex distribution of adrenergic receptors may induce the deterioration of coronary vessel function, eventually resulting in STEMI [ 16 ] .…”

“…In the event of life-threatening adverse effects, anagrelide should be discontinued [4] . Anagrelide effectively lowers platelet count by inhibiting thrombopoiesis, but its exact mechanism is not fully understood [16] . It is believed to work by suppressing transcription factors involved in thrombopoiesis [17] .…”