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.