The Hematology Journal (2005) 5, 589–590

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CASE REPORT

Acute myocardial infarction in sickle cell disease: a possible complication

of hydroxyurea treatment
André Fattori*,1, Robenı́lson Almeida de Souza1, Sara Terezinha Olalla Saad2 and Fernando
Ferreira Costa2
1
Hemocentro da UNICAMP, Campinas, Brazil; 2Faculdade de Cieˆncias Me´dicas da UNICAMP, Campinas, Brazil

We describe a 28-year-old man treated with hydroxyurea for sickle cell anemia, who was
admitted to the University Hospital with an acute myocardial infarction. The patient had
evolved high hematocrit values during his long-term hydroxyurea treatment, suggesting a
correlation between a possible increment in blood viscosity and the coronary occlusion without
previous lesions. Indeed, several studies associate vasocclusive episodes and severe clinical
course with high viscosity. Although hydroxyurea is considered an effective therapeutic option
for these patients, care should be taken to monitor hematocrit levels and possible complications.
Hematocrit and hemoglobin values of above 30% and 10.5 g/dl in SS patients on hydroxyurea
therapy should be avoided or closely monitored.
The Hematology Journal (2005) 5, 589–590. doi:10.1038/sj.thj.6200572

Keywords: sickle cell disease; hydroxyurea; myocardial infarction

Case report
A 28-year-old Afro-American man was admitted to the
University Hospital (UNICAMP, Campinas, Brazil)
with confusion and intense anterior chest pain lasting
for 10 h. The patient had been diagnosed with sickle cell
anemia since the age of 4 years. Electrocardiography
demonstrated ST elevation in leads II, III and AVF
(inferior heart wall) that evolved with T-wave inversion
and the development of Q waves. Creatinekinase and
creatinekinase M/B fraction elevation indicated an acute
myocardial infarction (AMI) as seen in Table 1. At
4 days after the episode of acute pain, a segmental
contractile dysfunction of the left ventricle was observed
in the echocardiography, but no coronary lesions or
obstructions were observed during cardiac catheteriza-
tion and angiography.
The patient had been previously treated with hydro-
xyurea for repeated vaso-occlusive crisis. Before treat-
ment, he maintained a hemoglobin level of
approximately 6.5 g/dl (hematocrit ¼ 20%), with mean
corpuscular volume 95 fl. At the time of acute myocar-
dial infarction the hemoglobin and hematocrit levels
were 10.7 g/dl and 31.3%, respectively (previous values
were consistently over 11.0 g/dl). The mean corpuscular
*Correspondence: A Fattori, Hemocentro da UNICAMP, Rua Carlos
Chagas, 480, Cidade Universitária ‘Zeferino Vaz’, 13083-970-Campinas-
São Paulo, Brazil; Tel/Fax: þ 55 19 32891089;
E-mail: afattori@unicamp.br
Received 1 March 2004; accepted 20 September 2004
volume was 123 fl and the fetal hemoglobin (HbF) level
was 10.2%, compared with 3.2% before treatment.
When the patient was admitted to the intensive care
unit, a careful history of all possible coronary disease
risk factors was obtained and we could not identify
hypertension, diabetes mellitus, cigarette smoking,
familial coronary disease or hypercholesterolemia.
Discussion
We suggest that the increment in hemoglobin values
may have contributed to increase blood viscosity, which
may be the precipitating factor of coronary obstruction.
AMI is not frequent in sickle cell disease. In a previous
description of 72 consecutive hearts studied after
autopsy, localized lesions described for AMI were
observed in only seven of them; however, a patchy
fibrosis was noted more often.1 In addition to these
observations, myocardial perfusion, as measured by
scintigraphy, demonstrated a 60% prevalence of perfu-
sion impairment in a group of 23 patients (average
1275 years old). In most of the patients, the perfusion
defect was not reversible after exercise or dipyridamole
stimulation.2 Taken together, these data indicate the
existence of a chronic myocardial hypoxia pattern,
leading to tissue necrosis and gradual deterioration of
heart function. The accelerated blood flow and high
oxygen content in the coronary circulation may possibly
explain the relatively low incidence of AMI among
sickle cell disease patients.
 Acute myocardial infarction in sickle cell disease
A Fattori et al
590
Table 1 Creatinekinase and M/B-creatinekinase fraction levels following initial chest pain
Time* 12 h 18 h
CPK (U/l) 1292 2498
CPK-M/B fraction (U/l) 40 111
*Elapsed time from the initial symptoms.
Blood viscosity increases proportionately according
to hematocrit and deoxyHbS concentration. In the
presence of HbS, oxygen delivery begins to fall at lower
hematocrit levels such as 20%.3,4 It is an important event
because it has been suggested that small fractions of
intracellular HbS may be polymerized as blood oxygen
pressure ðPO2 Þ declines and, despite it may not produce
morphological changes in erythrocytes, it is sufficient to
cause reduction in the cellular deformability, increment
in the total blood viscosity and consequently impaired
blood flow.5,6 Several studies, utilizing multivariate
analysis, suggested that higher hemoglobin levels and
low HbF are independently associated with higher pain
episode rates in sickle cell anemia patients and a higher
incidence of acute chest pain syndrome.7–9 In a group of
14 patients, which developed acute multiorgan failure
syndrome, a striking clinical feature was the relatively
high baseline hemoglobin values of these individuals.3
The vaso-occlusive phenomenon in the sickle cell
disease cannot be attributed to just one factor, but it is
better understood as a multifactorial process that
involves HbS level, hematocrit, blood oxygen content
and endothelial cell adherence.4,5,10 We hypothesize that
the significant increase in hematocrit in our patient,
along with only a modest increase in HbF, possibly
could be associated to an increase in blood viscosity,
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Conflict of interest statement
All authors of this text declare to have no financial and
personal relationships with other people or organiza-
tions that could inappropriately influence (bias) this
work.
Acknowledgements
We thank Dr Martin H Steinberg for kindly reviewing this
manuscript, and Dr Nicola Conran for English revision.
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