Case description:
An 11-year-old boy was referred to the pediatric hematology/oncology department of our institution for investigation of increased platelet count (1273×109/L). ET was diagnosed based on the hematological criteria including abnormal bone marrow findings (Fig. 1A), identification of the JAK2 V617F mutation, and absence of the BCR-ABL1 fusion gene.1, 2 His mother reported that he had intractable headache since age 2. The migraine-like severe headache was determined to be a vasomotor symptom of ET.10 Low-dose aspirin (100 mg/day) was administered to attenuate the microcirculatory symptom, which successfully ameliorated his headache.2, 10 However, the platelet count remained high for years, reaching 1250×109/L by the age of 18. Eventually, an intramuscular hemorrhage developed in the right buttock. Based on current epidemiological evidence, he was assumed to be at a high-risk of thrombohemorrhagic events. 2, 8, 11; therefore, cytoreductive therapy was started. Because of the concerns of the leukemogenic potential, we administered anagrelide (1.0 mg/day) instead of hydroxyurea.12, 13 We confirmed that cardiac function at baseline was normal to initiate drug therapy because of its toxic potential.7-9 Anagrelide successfully reduced the platelet count (range, 500–700×109/L). Clinically, there was no recurrence of thrombohemorrhagic events; however, he periodically complained of palpitations or vague chest sensations.
Five months after the anagrelide initiation, he was transferred to our cardiac center because of progressive worsening of precordial discomfort. On arrival, he was conscious with a body temperature, 36.5°C; heart rate, 87 beats/min; and systolic/diastolic pressure, 133/87 mmHg. The electrocardiogram showed sinus rhythm and prominent ST-T elevation in leads II, III, aVF, and V1-V3 with a reciprocal change (Fig. 1B). Blood tests revealed leukocytosis (white blood cell count of 14.7 × 109/L with neutrophils 81.5%), thrombocytosis (platelet count 894 × 109/L), and elevated markers for cardiac injury (troponin I 1288 pg/mL, creatine-kinase 9734 IU/L). He had no smoking history. Emergent coronary angiography revealed total middle right coronary artery (RCA) occlusion and spastic stenosis of the distal left anterior descending artery (LAD) (Figs. 1C and 1D). The RCA was recanalized by thrombus aspiration and intra-coronary nitroglycerin infusion, whereas the LAD was dilated with the intra-coronary nitroglycerin infusion alone (Figs. 1E and 1F).99mTechnetium-pyrophosphate scintigraphy was performed 3 days later; cardiac magnetic resonance imaging performed 10 days later demonstrated extensive myocardial infarction in the broad inferior and apical anterior wall (Figs. 2A-C).
Anagrelide was considered as a potential causative agent for the STEMI; thus, its administration was ceased. Instead, hydroxyurea (1000 mg/day) together with low-dose aspirin (100 mg/day) was initiated, which successfully controlled the platelet count (platelet count 500–700×109/L) without any recurrence of thrombohemorrhagic events. To date, the patient has been asymptomatic regarding cardiovascular manifestations, with the continuation of a renin-angiotensin-aldosterone-system inhibitor (enalapril, 10 mg/day) and coronary vasodilators (diltiazem, 200 mg/day; isosorbide, 40 mg/day).
Follow-up coronary angiography with the acetylcholine provocation test was performed 12 months later after a 2-day interruption of these vasodilators. Severe multivessel vasospasm was induced by intra-coronary acetylcholine infusion (Figs. 2D-G). Optical coherence tomography of the RCA (Fig. 2H) suggested intimal fibrotic changes without a remarkable atheromatous plaque; thus, continuous administration of the coronary vasodilators was required to prevent coronary ischemia recurrence.