4 Hospital Physician Board Review Manual www.turner-white.com
ing its bioactivity and resulting in up-regulation
of VCAM- 1.
16 Atelectasis worsens sickling locally
due to hypoxia, leading to local release of mediators of inflammation and ultimately microinfarction.
Recently, researchers have suggested that human
platelet antigen-5b allele may be a genetic risk
factor for the development of occlusive vascular
complications such as ACS in SCD.17 This allele
may ultimately lead to enhanced therapy or the
prevention of occlusive syndromes.
A single event or multiple events can trigger
the pathogenic mechanisms of ACS (ie, hypoxia,
hemoglobin S deoxygenation and polymerization, red cell sickling, and microvasculature occlusion), which evolve through a final pathway where
hypoxia causes further sickling, leading to a self-perpetuating cycle. Initiating processes include
pulmonary infection, fat and bone marrow embolism, pulmonary infarction, thromboembolism, or
in situ thrombosis. In addition to these processes,
atelectasis from poor chest movement secondary
to pain from thoracic bone infarction and decreased
respiratory stimulation due to opiates can worsen
the hypoxia, inducing further red cell sickling.
These specific etiologies result in syndromes that
are clinically similar and best described as ACS.
The most common causes of the syndrome are
infection and pulmonary fat embolism, although a
specific cause often is not identified. Contrary to
the prior reports of gram-positive bacterial infec-
tions causing ACS,
6,18 subsequent studies suggest
that atypical organisms may be the more likely
10,19 The most common infective organisms
found in more recent studies are Chlamydia pneu-
moniae and Mycoplasma pneumoniae followed by
respiratory syncytial virus.
10,19 Up to 27 pathogens
have been implicated as etiologic factors in ACS.
The incidence of streptococcal infection has been
decreasing, likely secondary to prophylactic vaccination in patients with SCD.
During vaso-occlusive crisis, bone ischemia can
lead to infarction and necrosis of bone marrow and
release of the marrow contents, including fat, into
the blood stream. Pulmonary fat emboli resulting
from this pathologic process is presumed to be the
most frequent single recognizable cause of ACS.
Patients with fat embolism are usually older.
11 Thoracic bone infarction also contributes to the development of the syndrome as it can lead to splinting
and atelectasis, which may result in ineffective
clearance of secretions, promoting infection. As
shown by bone scans in a study by Bellet et al,20
thoracic bone infarction (ribs and vertebrae) occurs in up to 39.5% of sickle cell patients hospitalized due to acute chest or back pain.
Thromboembolism or in situ thrombus are etiologic considerations in ACS21 given the hypercoagulable state induced by hypoxia and decreased
levels of NO and the higher incidence of thromboembolism in patients with SCD. Pulmonary
infarction is the diagnosis of exclusion when other
specific etiologies are eliminated.
Studies have linked asthma to ACS among patients with SCD. Sylvester et al22 in his study showed
that 18% of the children with a history of ACS were
taking medications to help with their asthma compared to only 5% with no history of ACS. These
children on medications for their asthma had been
diagnosed with asthma approximately 3. 5 years
before the onset of of ACS.
1 Children with asthma
and SCD also have more vaso-occlusive complications, including ACS.23 These findings may suggest
an association between the 2 diseases or that asthma, prevalent among inner-city African-American
populations, may simply exacerbate SCD and trig-