Home > Browse Topics

<< Sickle Cell Disease And Other Hemoglobinopathies: Approaches To Emergency Diagnosis And Treatment


 Acute Chest Syndrome

ACS is a descriptive term for an acute pulmonary illness in a patient with SCD. It comprises some combination of new pulmonary infiltrate, chest pain, fever, and hypoxia. In addition to these findings, the patient may present with cough, dyspnea, tachypnea, or wheezing.99 ACS is the leading cause of death and second leading cause of hospitalization among patients with SCD.100-102 While some patients present to the ED with ACS, many cases develop after a patient is hospitalized for a vaso-occlusive crisis.103

The etiology of ACS is multifactorial, and the pathogenesis, which may involve both infectious and noninfectious causes, is not completely understood. Commonly associated infectious agents include Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae.42 Other agents include Chlamydia pneumoniae, Mycoplasma pneumoniae, and respiratory syncytial virus.

In addition to infectious causes, lung infarction from in situ thrombosis or thromboembolism is thought to play a major role in the pathogenesis of ACS. Intravascular sickling likely causes most cases of pulmonary vascular occlusion.104 Autopsy studies have identified particles of fat and bone marrow in these pulmonary thrombi, suggesting necrotic bone marrow as an embolic source.105,106 Embolization from clots in the systemic veins is rare in sickle cell patients.41 In one large study, fat embolism or in situ thrombosis/infarction was the likely etiology of ACS in almost 34% of patients, with or without co-existent infection.103 Rib infarcts may also play a role in ACS. These infarcts produce local swelling and pleuritic pain, resulting in hypoventilation, atelectasis, and pneumonia.28,107

Adult patients with ACS tend to be afebrile, have severe pain, and often have multilobar disease combined with high mortality.108 In contrast, children are more often febrile and usually present with cough without chest pain. Children with ACS typically have milder disease, usually due to infection.

While the chest film is important in diagnosing ACS, the initial radiograph is normal in almost half of patients who ultimately develop the syndrome.42 Even when positive, chest radiography often underestimates vascular damage and accompanying physiologic derangement. The degree of hypoxia measured by pulse oximetry or by arterial blood gas is usually out of proportion to the findings seen on chest x-ray.109


Despite the increased awareness of ACS, the diagnosis is often delayed and the optimal treatment remains unknown. 103 Early administration of broad-spectrum antibiotics, targeted toward both usual and unusual pulmonary pathogens, is reasonable. Inclusion of a macrolide or fluoroquinolone provides coverage for atypical organisms such as chlamydia or mycoplasma. Some authorities recommend routine treatment with bronchodilators. Incentive spirometry may help prevent or decrease the manifestations of ACS, especially among those with rib infarctions or atelectasis.110

One randomized, double-blind, placebo-controlled trial showed that IV dexamethasone (0.3 mg/kg q12h x 4 doses) had a beneficial effect in hospitalized children with mild to moderately severe ACS. Mean hospital stay was shorter in the dexamethasone-treated group, and the steroids prevented clinical deterioration and reduced the need for blood transfusions.111

Some patients with ACS require transfusions with leukocyte-depleted red blood cells with a goal to raise the hematocrit to no more than 30%-35%. More severely ill patients may require exchange transfusion to rapidly raise the hematocrit to greater than 35%. Anticoagulation is indicated when the diagnosis of thrombosis or embolism is strongly suggested based on a combination of clinical history and imaging studies such as CT or angiography. Consultation with a hematologist should be sought when indicated.


Also known as hand-foot syndrome, dactylitis may be the earliest manifestation of SCD.48,112 This condition is usually seen in children younger than 6 months of age, but can occur up to 4 years of age.19,112 Physical exam reveals swelling of the hands or feet, pain, and fever. There may also be erythema, mimicking osteomyelitis,113 and the WBC count and sedimentation rate may be elevated. Initial radiographs are normal, but radiographs taken several days after the onset of symptoms may show periosteal elevation. Treatment is supportive, with analgesia, hydration, and warm compresses. Symptoms are usually self-limited.80

Acute Splenic Sequestration

Acute splenic sequestration is a condition in which the spleen suddenly traps a large number of red cells. This causes severe anemia (decrease in hemoglobin by 20% or more), an enlarging spleen (by at least 2 cm from baseline), hypovolemia, and mild thrombocytopenia.6 The incidence of acute splenic sequestration peaks at 1-2 years of age19 and is most common in children with HbS disease.114 Children with HbS disease have a 30% probability of having an acute splenic sequestration event by age 5, and mortality can approach 15% per event.115 On rare occasions, children with variant disease or adults with minor hemoglobinopathies can develop acute splenic sequestration as well.28

Acute splenic sequestration can recur. Up to 50% of children will have a second episode, usually within
two years.116,117


The presentation of acute splenic sequestration is generally not subtle. Children will usually arrive in extremis—pale, tachycardic, and hypotensive. A massive spleen will dominate the belly. Diagnostic tests apart from a stat hemoglobin are generally unnecessary, but a bedside ultrasound of the abdomen could help rule out intraperitoneal fluid (if splenic rupture is suspected). Once the child is stabilized, CT scan of the abdomen may be helpful if the diagnosis remains in doubt or if there is concern for a splenic abscess.118


Acute splenic sequestration is life-threatening. Because hypovolemic shock is more lethal than anemia, immediately give large amounts of IV crystalloid (20-40 cc/kg). After stabilization of blood pressure, begin the transfusion. Transfusion is not without risk, as an acutely enlarged spleen will release sequestered blood a few hours after transfusion. Hemoglobin can then rise dramatically, and the increased blood viscosity will worsen perfusion.6 For these reasons, some experts suggest utilizing an exchange transfusion to avoid this complication in seriously ill patients with acute splenic sequestration.83

The goal of transfusion during acute splenic sequestration is to achieve a post-transfusion hemoglobin level of 6-8 g/dL. A useful guide for transfusion is as follows: Give a volume of red cells (in mL/kg) equal to the pretransfusion hemoglobin level. For example, if the initial hemoglobin level is 4 g/dL, give 4 mL/kg of packed red blood cells initially.6 Employ diuretics if hypervolemia or congestive heart failure develops post transfusion.

Splenectomy is not always indicated for acute splenic sequestration. Patients can often be managed with chronic transfusions until they become older than 3 years, at which time the risk of splenic sequestration will diminish. Partial splenectomy is also an option.6

Anemias In Sickle Cell Disease
Hyperhemolytic Crisis

Hyperhemolytic crisis (HC) involves a higher-thannormal rate of hemolysis and often occurs in conjunction with a vaso-occlusive crisis. It is occasionally precipitated by infection. Hyperhemolysis can also occur when an individual with SCA has a co-existent G6PD deficiency and is given certain medications, such as sulfa drugs or nitrofurantoin. In addition to pain, patients with HC may present with fatigue, increased scleral icterus, and jaundice.

On laboratory analysis, HC is characterized by a decrease in hemoglobin, higher-than-usual reticulocyte count, increased indirect bilirubin, and increased LDH.1 HCs are typically self-limited,1 but transfusion may be necessary for severe anemia.

Aplastic Crisis

During an aplastic crisis, there is a temporary arrest of red cell production; thus, reticulocytopenia (generally < 2%) is the hallmark of this condition. Patients will demonstrate a variable decrease in hemoglobin. Usually only erythropoiesis is affected, but neutropenia and thrombocytopenia are occasionally seen.6 Aplastic crisis is often caused by parvovirus B19. In one study, 80% of such cases of aplastic crisis were associated with this organism.119

Aplastic crisis most commonly occurs in children and usually resolves spontaneously within 5-10 days. Treatment is mainly supportive, but transfusion may be necessary. Isolation is warranted to prevent contact with pregnant women and other sickle cell patients. Indications for transfusion include 25% or greater decrease in hemoglobin level from baseline with a low reticulocyte count and severe symptoms from the anemia.120

Other Forms Of Anemia

Megaloblastic anemia is sometimes seen in sickle cell patients and can result from folate deficiency. Folate becomes depleted as a result of enhanced erythropoietic activity from chronic hemolysis. Patients should be taking 1 mg of folate orally each day.6 A microcytic anemia may reflect iron deficiency, especially in a menstruating female, a child with a period of rapid growth, or a co-existing thalassemia. Supplemental iron should not be given unless a deficiency is documented due to the possibility of iron overload.6

Transfusion Therapy
Patients with SCD are chronically anemic and typically have hemoglobins between 7 and 8. Because of physiologic adaptations, they tolerate the anemia well. On occasion, however, some patients with SCD will require transfusions in the ED or shortly after hospitalization. In one study of 520 transfusions in 197 patients, indications for transfusion included aplastic crisis (102), ACS (90), acute splenic sequestration (75), stroke (62), septicemia (46), hypoplasia (40), hypersplenism (34), surgery (31), gastroenteritis (10), and miscellaneous (30).121

When transfusing a patient with SCD, consider the need for special types of blood. Leukocyte-depleted packed red blood cell preparations are recommended, especially in children. These decrease febrile reactions, minimize allo-immunization to the human leukocyte antigen, and reduce the risk of cytomegalovirus transmission. Children who are candidates for bone marrow transplantation should receive irradiated cellular blood products whenever possible.1,6

Exchange transfusions involve replacing all or part of the patient's blood with stored blood. This is not generally an ED intervention. Exchange transfusions cause less iron accumulation, but because of the volumes involved expose the patient to greater risk of infection and allo-immunization. It requires central venous access and is more expensive than simple transfusion. Nevertheless, in the acute setting it avoids the potential problem associated with increased blood viscosity that is sometimes
seen in standard blood transfusions.

Some patients with SCD suffer an unusual and life-threatening hemolytic transfusion reaction when given blood.122 Consultation with a hematologist and administration of IV immune globulin and steroids may be of value in such circumstances.122 Vichinsky offers a comprehensive review on transfusion issues in SCA in a recent issue of Seminars in Hematology.123

Fever In The Sickle Cell Patient

Fever is common in uncomplicated painful crises and does not necessarily indicate infection.57 However, some patients with fever and SCD are infected and at high risk for morbidity or mortality, especially in the first several years of life. Perhaps 2%-6% of febrile children with sickle cell suffer bacteremia.124,125 (See Table 3.)

One study reviewed febrile episodes in patients less than 17 years old with homozygous SCD who presented with an axillary temperature of 39.0°C (102.4°F) or higher. There were 165 events in 144 patients; bacteremia occurred in only in 10 (6.1%) and UTIs in four (2.4%). No child had meningitis. ACS was responsible in 36 (21.8%) events, and a painful crisis was the only pathology identified in 20 events (12.1%). (Some children had both infection and painful crisis.) It is interesting that painful crisis and ACS were the most common complications associated with high fever, while bacteremia and UTI
were infrequent.124

Another retrospective study examined all children admitted to a children's hospital for SCD and fever over a 27-month period. Of 517 admissions, there were only 10 (1.9%) positive blood cultures. Positive cultures occurred more frequently in children less than 2 years old and in those with indwelling central venous catheters. All but one child with bacteremia had an ill appearance, a focus of infection, or a central venous catheter in place. In view of their findings, the authors suggested that outpatient management strategies with antibiotics in selected children with SCD and fever merit further study.125

It would be nice if there were a laboratory test that could detect serious bacterial illness in children. Unfortunately, the CBC is not such a test. In one study, authors compared hematologic parameters in 23 children with SCD with proven bacterial infection (Group A) to those of 22 similar patients with fever but without evidence of bacterial infection (Group B).126 The total WBC count and percentage of segmented leukocytes were similar in both groups. While the absolute band counts were often greater in the Group A patients, the sensitivity and specificity of elevated band counts were relatively low. The authors concluded that "No aspect of the CBC can be used to guide major management decisions in febrile children with SCA and potentially life-threatening infection."126

A study published by Williams et al examined the safety of outpatient treatment of selected children with SCA and fever. In the larger study, children from 6 months to 12 years of age with sickle hemoglobinopathies who had temperatures greater than 38.5°C were randomly assigned to treatment as either inpatients or outpatients.127 The authors excluded children whom they considered high risk from randomization. High risk was defined as having any of the following:
  • Temperature > 40°C (104°F)
  • WBC count < 5000/mm3 or > 30,000/mm3
  • Pulmonary infiltrates
  • Hemoglobin level < 5 g/dL
  • Dehydration
  • Severe pain
All patients received an initial IV dose of ceftriaxone (50 mg/kg), and those treated as outpatients returned 24 hours later for a second dose of ceftriaxone. Slightly more than 20% of the outpatient group required hospitalizations in the subsequent two weeks after treatment. All of these children did well, and most were hospitalized for reasons not directly related to their SCD. When compared to the inpatient group, outpatient treatment saved a mean of $1195 per febrile episode.127 The authors also suggest that IM ceftriaxone could be substituted for IV medication based on the known pharmacokinetics of IM ceftriaxone.

A smaller, earlier study also showed that certain febrile children with SCD may be safely managed with parenteral ceftriaxone and outpatient therapy.128

Neurological Complications

Cerebrovascular disease is a devastating complication of SCD and is a leading cause of death in children and adults with the disease.17,102 Vascular problems of the brain, primarily localized to the internal carotid, middle cerebral, and anterior cerebral arteries, are usually due to large-vessel disease.129,130 Early in their lives, patients with SCD are at risk for infarction, but as they age, an increased risk of hemorrhage due to rupture of weakened collateral vessels develops.131

The Cooperative Study of Sickle Cell Disease followed more than 4000 patients with SCD over a 10- year period, producing valuable data on prevalence, incidence, and risk factors for stroke in sickle cell patients.132 The overall age-specific incidence of first stroke in HbSS disease is 0.13% at ages less than 24 months, increases to 1% at age 2-5 years, then decreases to 0.79% at age 6-9 years. The risk remains low until a second peak after age 50, when the incidence rises to 1.3%. Hemorrhagic stroke was most common among patients 20-29 years old.132,133

Presentation And Diagnosis

Patients with SCD may present with a wide variety of neurological complaints, including headache, seizures, altered mental status, or focal neurologic deficits.134 Those with significant findings generally require an emergent brain CT scan.


Treatment of neurological complications of sickle cell depends, of course, on the particular disease, whether it be hemorrhage or ischemia. There have been few studies of stroke in patients with SCD, and these patients are usually not included in clinical trials that investigate the acute treatment of stroke.133

Studies show that transfusion therapy can prevent stroke in children with SCD who are at high risk for a cerebrovascular accident.47,132,133,135,136 However, there are no data to suggest that it is useful in the acute setting.133

Thrombolytic agents for ischemic stroke have never been studied in the sickle cell population. Though considered by some to be the standard of care for acute ischemic stroke, the use of thrombolytics remains controversial in all subgroups, much less in SCD.

Genitourinary Complications

There are a number of genitourinary complications seen in SCA. The primary renal complications seen in SCD include hematuria, nephrotic syndrome, and, in rare circumstances, renal failure.

Hematuria is usually self-limited, resolving with bed rest alone. It may occur in those with sickle cell trait, and this diagnosis should be considered in the patient of African descent who presents with painless hematuria.137 Transfusion may be needed if the hematuria is severe.138 Years of glomerular hyperfiltration results in renal damage and the inability to concentrate urine, but chronic renal failure in SCD is uncommon overall.6 A prospective longitudinal study followed a cohort of 725 patients with SCA and found chronic renal failure in only 4.2 %.139

The most important genital complication of SCD is priapism. Priapism occurs when sickled cells congest the corpora and prevent emptying of blood from the penis. It is a prolonged, usually painful penile erection not initiated by sexual stimuli.140 The priapism that is seen in sickle cell patients is termed a "low flow" or ischemic priapism. Low-flow priapism is a time-sensitive emergency, as irreversible cellular damage and fibrosis can occur if treatment is not administered in 24-48 hours.140 (A full discussion on priapism can be found in the November 2000 issue of Emergency Medicine Practice, "Male Genitourinary Emergencies: Preserving Fertility And Providing Relief.") Treatment of priapism in sickle cell patients includes analgesia, hydration, oxygen, and, occasionally, exchange transfusion. These measures are successful in about 80% of patients.141 If simple interventions fail, corporal aspiration and injection of a vasoconstrictor are occasionally successful in sickle cell patients. 141 Urology consultation is indicated.

Ophthalmologic Complications

The most serious ocular emergency in sickle cell patients is hyphema in the setting of trauma. The sickled cells tend to obstruct the flow of aqueous humor and may result in elevation of intraocular pressure and subsequent acute angle closure glaucoma. If the intraocular pressure is 24 mmHg or greater in the setting of hyphema, treatment for acute angle closure glaucoma should be initiated. Urgent ophthalmologic consultation should be obtained in all sickle cell patients with hyphema.115

Other Articles Similar To This One:

EMplify, the new Emergency Medicine Practice podcast, is now available


About EB Medicine:


Accredited By:


Endorsed By:

HONcode HONcode


Last Modified: 07/23/2017
© EB Medicine