Page 1230 - Hematology_ Basic Principles and Practice ( PDFDrive )

1076 Part VII Hematologic Malignancies

to respiratory alkalosis that in turn promotes the synthesis of Common symptoms include loud snoring and breathing pauses
2,3-bisphosphoglycerate (2,3-BPG), facilitating increased oxygen observed by a bed partner, feelings of nonrefreshing sleep, and excess
delivery to tissues. daytime sleeping. Although the evidence is largely anecdotal, second-
The practical relevance of an elevated hematocrit level in this ary polycythemia is a widely recognized complication of long-standing
clinical situation is whether and at what level it is harmful or benefi- sleep apnea, being found in 5–10% of those with nocturnal apnea
cial. An extremely elevated hematocrit level may be detrimental to and hypopnea. Similarly, 25% of those with unexplained polycythe-
optimal oxygen delivery. Extreme but not moderate polycythemia mia are subsequently found to have sleep apnea. The mechanism by
caused by chronic hypoxia may affect systemic vascular function by which sleep apnea causes polycythemia is unclear. Differences in EPO
altering blood viscosity, vessel wall shear stress, reduced endothelial levels between normoxic and hypoxemic patients referred for sus-
cell–derived nitric oxide release, and increasing the secretion of pected sleep apnea have not been documented. Obstructive sleep
endothelin. Although it is widely accepted that polycythemic pediat- apnea is also associated with an increased risk of developing cardio-
ric patients with cyanotic heart disease are at an increased risk for vascular diseases, including systemic hypertension, pulmonary
developing cerebrovascular accidents, the literature provides conflict- hypertension, cardiac arrhythmias, atherosclerosis, ischemic heart
ing data as relates to the prevalence of such events among adults. A disease, and stroke. Intermittent hypoxia is thought to be a major
10–13.6% prevalence of stroke and transient ischemic attacks (TIAs) cause of cardiovascular complications. These patients undergo
has been reported in a cohort of adult patients with cyanotic heart repeated episodes of hypoxia and normoxia. The hypoxia leads to
disease, but others have claimed that such events are rare. ischemia, and the reoxygenation causes a sudden increase of oxygen.
Iron deficiency occurs in more than 30% because of the total This reoxygenation phase results in the production of reactive oxygen
depletion of iron stores to support erythropoiesis. Microcytic RBCs species and the promotion of oxidative stress, leading to an inflam-
are, however, rarely found, and despite the iron deficiency, these matory response and the development of vascular complications.
patients frequently have normal mean corpuscular volumes and high Conversely, PV may induce central sleep apnea by decreasing
mean corpuscular hemoglobin concentrations, which might maxi- cerebral blood flow to diencephalic respiratory centers, and patients
mize the amount of hemoglobin within an individual RBC, thereby so affected can have complete resolution of their sleep disorder with
maximizing oxygen delivery. In the past, compensatory erythrocytosis normalization of their blood counts.
was thought to lead to an increased plasma viscosity, leading to a
compromised microcirculation, resulting in such symptoms as head-
ache, sluggish mentation, dizziness, blurry vision, muscle weakness, Pickwickian Syndrome and Polycythemia
or paresthesias. In reality, such symptoms are rare in patients with
chronic compensated secondary erythrocytosis, and the secondary Pickwickian syndrome or obesity–hypoventilation syndrome, seen in
erythrocytosis is viewed as a physiologically desirable response to morbidly obese individuals, is characterized by chronic hypoxemia
chronic hypoxia. The symptoms delineated above are likely attribut- and hypercapnia caused by alveolar hypoventilation, with a resultant
able to decreased tissue oxygen delivery rather than hyperviscosity. increase in EPO production, polycythemia, and cor pulmonale. The
The treatment of hyperviscosity secondary to erythrocytosis in three principal causes are the high cost of the work of respiration in
cyanotic heart disease with prophylactic phlebotomy is rarely used. morbidly obese individuals, dysfunction of the respiratory centers,
In fact, phlebotomy has been reported to have harmful rather than and repeated episodes of nocturnal obstructive apnea. Effective treat-
beneficial effects in adults with cyanotic congenital heart disease. ments include surgically induced weight loss, nasal continuous posi-
Because almost one-third of these patients are iron deficient even tive airway pressure ventilation, and the respiratory stimulant
though their RBC indices do not reflect this, routine assessment of medroxyprogesterone acetate.
the patient’s iron status is suggested with gradual supplementation
with sufficient iron to attain appropriate compensatory levels of
erythropoiesis but avoiding excessive sudden increases in the degree Polycythemia Caused by High Altitude
of erythrocytosis. The present evidence indicates that prophylactic
phlebotomy promotes the development of iron deficiency, decreases Polycythemia caused by the hypoxic conditions encountered by high-
exercise tolerance, and increases the number of cerebrovascular events. altitude dwellers would appear at first glance to represent a universal
Currently, experts in this field recommend that phlebotomy should adaptive process to altitude. High altitude results in hyperventilation,
be restricted to individuals with symptoms with extreme erythrocy- alkalosis, and shifting of the O 2 dissociation curve to the left, leading
tosis (hematocrit >65%) and preoperatively to improve hemostasis. to the impaired release of O 2 from hemoglobin and ultimately tissue
Clinical data to justify these recommendations are lacking. Phlebot- hypoxia. This tissue hypoxia results in markedly increased EPO
omy should be followed by the infusion of an equal volume of fluids production, leading to increased plasma iron turnover, reticulocytosis,
to maintain intravascular volume and blood flow, as well as to provide and a rising hematocrit level. Residents of the Andes Mountains who
a dilutional effect to reduce the hematocrit level. Hydroxyurea live 4200 m above sea level frequently have 30% higher hematocrit
therapy has been used occasionally to reduce erythropoiesis in this levels than individuals living at sea level.
situation to reduce the need for phlebotomy, but little evidence exists People native to high altitudes (highlanders) live in a hypobaric
for this approach. The superiority of hydroxyurea therapy versus hypoxic environment characterized by a low ambient partial pressure
phlebotomy therapy has not been documented. Hydroxyurea might of oxygen. In response to this environment, they develop alveolar
act not only by suppressing RBC production but also by promoting hypoxia, hypoxemia, and polycythemia. Healthy highlanders develop
macrocytic RBC formation, thereby increasing RBC deformability pulmonary hypertension, right ventricular hypertrophy, and an
and decreasing RBC adhesiveness. increased amount of smooth muscle cells in the distal pulmonary
Chronic oxygen therapy in patients with severe COPD has arterial branches, which leads to increased pulmonary vascular resis-
resulted in relief of hypoxia and a modest reduction in hematocrit tance and pulmonary artery pressure compared with individuals
levels. Pharmacologic interventions, including theophylline, inhaled living at sea level. The importance of these structural changes in the
nitric oxide, sildenafil, or antagonism of the renin–angiotensin pulmonary vasculature in highlanders is confirmed by the slow
pathway with losartin, may also reduce the degree of pulmonary decline of pulmonary artery pressure, which is normalized after living
hypertension or secondary erythrocytosis. for 2 years at sea level. Despite these adaptive changes, healthy
highlanders are able to perform physical activities similar to or often
even more strenuous than those living at sea level. In fact, there are
Obstructive Sleep Apnea–Induced Polycythemia differences in ventilation rates between athletes performing at sea
level and those at high altitudes. Ventilation rates of athletes increase
Obstructive sleep apnea syndrome is characterized by repetitive epi- normally during exercise at sea level, but relative hypoventilation
sodes of partial or complete obstruction of airflow during sleep. occurs in highlanders. This relative hypoventilation is characteristic