Page 794 - Williams Hematology ( PDFDrive )

768 Part VI: The Erythrocyte Chapter 49: Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities 769

Hydroxyurea should be offered to all patients with any of the risk factors
for increased mortality described above. 162
Asthma, Abnormal Pulmonary Function Tests, and Airway
Hyperreactivity. Asthma is a common comorbidity with high-
er-than-average prevalence in patients with SCD and is associated with
increased risk of ACS, VOE, stroke, and mortality. Airway hyperreac-
tivity as evidenced by a positive bronchodilator response on pulmonary
function testing, irrespective of baseline function, and in response to cold
air or methacholine challenge, is seen in approximately two-thirds of
SCD patients. Inflammation, hypoxemia, and increased oxidative stress
associated with asthma may contribute to the vasculopathy of SCD. 163
Pulmonary function tests collected as part of the Cooperative Study
of Sickle Cell Disease (CSSCD) revealed abnormalities in 90 percent of
the 310 patients, with the majority having restrictive lung disease .
Asthma treatment follows general treatment guidelines as in the
non-SCD populations. 164,165

Cardiac Manifestations
Anemia in SCD results in an elevated cardiac output secondary to
an increased stroke volume with minimal increase in heart rate. 166,167
Clinical manifestations of a hyperdynamic circulation include a force-
Figure 49–8. Anteroposterior view of chest radiograph depicting ful precordial apical impulse, systolic and diastolic flow murmurs, and
bilateral, patchy, lung infiltrates in a 30-year-old female with sickle cell tachycardia that may increase during periods of increased hemody-
disease and evolving acute chest syndrome. namic stress. Diastolic left ventricular dysfunction may begin in early
childhood and is an independent risk factor for death, with even greater
risk of mortality in those having PH. Left ventricular hypertrophy is
for ACS, which was seen in 22 percent of adult patients in the National common and progressive with age; left ventricular dysfunction is a late
Acute Chest Syndrome study. 154 event. Myocardial infarction is an underrecognized problem in SCD.
The treatment of ACS includes oxygenation, incentive spirome- Epicardial coronary artery disease is rare; microvascular ischemia is
try, adequate pain control to avoid chest splinting, antimicrobial ther- likely causative. Sudden cardiac death has been reported in 40 percent of
apy that always covers atypical bacteria and influenza when indicated, patients in an autopsy series. 168–170 Previously sudden cardiac death was
avoidance of overhydration, use of bronchodilators, and red cell trans- ascribed to narcotic overdose; currently, it is thought to be secondary
fusion to decrease intrapulmonary sickling. 152,155–160 The use of gluco- to cardiopulmonary causes in the majority of cases. QTc prolongation,
corticoids may attenuate the course of ACS; however, its use is not well atrial and ventricular arrhythmias, nonspecific ST-T wave changes are
established and readmission rates for VOE after ACS resolution are common in SCD patients. Patients presenting with chest pain should
increased. sPLA has been recognized as a predictor of ACS; however, have a thorough evaluation to rule out cardiac disease. Cardiac mag-
153
2
a clinical trial investigating early transfusion based on sPLA elevation netic resonance may be a good modality to image microvascular flow
2
closed because of poor accrual. Hydroxyurea therapy should be offered and quantitate cardiac iron overload. 171,172 Blood pressure in patients
to all patients with a history of ACS because it reduces the incidence by with SCD is significantly lower than age-, sex-, and race-matched con-
173
50 percent in adults and 73 percent in children. 161 trols, partly secondary to anemia. Relative hypertension is associated
Pulmonary Hypertension PH, defined by a resting mean pulmo- with end-organ damage. Diuretics may be used, keeping in mind that
nary arterial pressure of 25 torr or higher on right-heart catheterization, SCD patients have obligate hyposthenuria and are prone to dehydra-
is seen in 6 to 11 percent of SCD patients. An elevated tricuspid regur- tion, which can precipitate a VOE.
gitant velocity of 2.5 m/s has a positive predictive value of 25 percent for
PH in SCD and is seen in one-third of these patients. PH, as defined by Central Nervous System
right-heart catheterization, elevated tricuspid regurgitant jet velocity of Originally thought to be a small vessel disease, stroke in SCD is a mac-
2.5 m/s or higher, and a serum N-terminal pro–brain natriuretic pep- rovascular phenomenon with devastating consequences that affects
tide (NT-pro-BNP) level of 160 pg/mL or higher, confers an increased approximately 11 percent of patients younger than 20 years of age. 174,175
mortality risk. 162 Risk is highest in the first decade of life followed by a second smaller
Abnormalities in NO metabolism, hemolysis, and inflammation peak after age 29 years. Ischemic stroke is most common in children
contribute to the pathophysiology of PH. Parenchymal lung disease and older adults, whereas hemorrhagic stroke predominates in the third
162
175
from repeated episodes of ACS and thromboembolism are other causal decade of life. Recurrent stroke is most common in the first 2 years
factors. following the primary event. Silent infarcts, defined as an increased
176
Clinical symptoms of PH include fatigue, dizziness, and dyspnea T2 signal abnormality on magnetic resonance imaging (MRI), begins
on exertion, chest pain, and syncope. These may be unrecognized as in infancy and has a cumulative incidence of 37 percent by age 14 years.
being related to PH, as PH is often undiagnosed in patients with SCD. They occur in watershed areas of the brain, are not predicted by abnor-
PH should be treated following guidelines set for the treatment of mal transcranial Doppler (TCD) velocity, and may progress despite
primary PH unrelated to SCD. Two trials looking at bosentan (endo- chronic transfusion. 177–180 There is evidence of neurocognitive decline in
thelin receptor antagonist) in SCD patients closed because of sponsor asymptomatic adults despite having normal brain imaging that is attrib-
withdrawal. A trial of sildenafil was halted early because of increased uted to anemia and hypoxemia. 154
incidence of VOE. Patients who have venous thromboembolism in Cerebral blood flow is significantly increased in SCD because
the setting of PH should be considered for indefinite anticoagulation. of chronic anemia and hypoxemia, but does not increase further in

Kaushansky_chapter 49_p0759-0788.indd 769 9/18/15 3:01 PM