Last revised May 21, 2000
Winfred C. Wang, M.D.
St. Judes Children's Research Hosptial
Memphis, Tennessee


Acute exacerbation of anemia in the patient with sickle cell disease is a significant cause of morbidity and mortality. The most common processes leading to these "crises" are acute splenic sequestration and transient erythroid hypoplasia.



Acute splenic sequestration is caused by intrasplenic trapping of red cells causing a precipitous fall in hemoglobin level and the potential for hypovolemic shock. With the recent decline in mortality from pneumococcal sepsis, ASSC has become a leading cause of death in children with sickle cell disease. ASSC may be defined by a decrease of at least 2 g/dL from the steady-state hemoglobin concentration, evidence of increased erythropoiesis such as a markedly elevated reticulocyte count, and an acutely enlarging spleen. ASSC has been reported as early as 5 weeks of age (1) and in adults (2), but in most cases first attacks occur between 3 months and 5 years of age. They are often associated with viral or bacterial infections; acute chest syndrome occurred in 20% in one series (3). The usual clinical manifestations are sudden weakness, pallor, tachycardia, tachypnea, and abdominal fullness. ASSC has been reported in 30% of children with sickle cell anemia in Jamaica (3) and 7.5% of children seen at Duke University (4). The mortality rate for first attacks was 12% in Jamaica (5). Recurrent splenic sequestration crises are common, occurring in approximately 50% of those who survive the first episode, and the mortality rate in these patients may be 20% (5). There are no clear prognostic factors for the occurrence of ASSC, although the Hb F level at 6 months of age was somewhat lower in children who developed this complication (3). Although ASSC occurs most commonly among children with Hb SS, it has been reported in 5% of children with Hb SC disease at a mean age of approximately 9 years (6) and in adults with Hb SC disease (7).


Supporting evidence was sought from articles identified through a search of MEDLINE using the terms sickle cell disease and spleen. When evidence was identified, it was graded according to the standard criteria of validity and methodologic quality using a level of evidence ranking system from I to V. Most of the literature regarding management of ASSC comes from retrospective reviews of experience at single institutions.

Treatment -- Summary of Reports

The immediate treatment of acute splenic sequestration is directed toward correction of hypovolemia with red blood cell transfusion. Because severe ASSC can be fatal within a few hours, emergent transfusion is required. Once transfusion is employed, red cells sequestered in the spleen are remobilized, splenomegaly regresses, and the hemoglobin level increases, often to a level greater than predicted on the basis of the volume of red cells administered.

The high rate of recurrent splenic sequestration is reminiscent of the risk of recurrent stroke in patients who have suffered an initial event and greatly influences subsequent management, which may be divided into: observation only, chronic transfusion, and splenectomy. The indications for these approaches are not clearly defined. Questions which bear on management decisions are: does splenectomy increase the risk of invasive infection above that of the patient with an infarcted spleen? Does a partial splenectomy allow maintenance of some splenic function? Does chronic transfusion effectively restore splenic function? Does it maintain the potential of the spleen for sequestration by delaying autoinfarction?

Observation. Because of the high risk of recurrence and significant mortality of ASSC, observation has been recommended only in situations in which ASSC is unusually mild and does not require an initial transfusion (8).

Chronic transfusion. Rao and Gooden (9) treated 11 children with "subacute splenic sequestration" with short-term transfusion for 1-3 years. Seven patients had recurrent sequestration when transfusions were discontinued around 5 years of age and were subsequently splenectomized. However, mortality was absent and the authors concluded that the time gained from short-term transfusion therapy was beneficial in reducing the risk of acute sequestration and temporarily reversing splenic dysfunction. By contrast, Kinney et al. (5) compared short-term transfusion (n=12) with observation (n=7) and immediate splenectomy (n=4) in a group of 23 children with ASSC. Despite a reduction in Hb S concentration to <30% in the chronically transfused patients, the risk of recurrent sequestration appeared unaffected by transfusion. Seven of 10 evaluable patients on chronic transfusion had recurrences either during the transfusion period or shortly after transfusion was discontinued; 4 of 7 patients who were observed had recurrences. Overall, splenectomy was performed in 61%. The authors concluded that short-term transfusion to prevent recurrent splenic sequestration was of limited benefit. An intermediate recommendation came from Grover and Wethers (10), who advised a year or more of long-term transfusion therapy for the child with ASSC under age 3 and prompt splenectomy after the first episode of ASSC in the child >5 years of age.

Topley et al. (4) described the close relationship between episodes of ASSC and the subsequent development of hypersplenism, which occurred in one-third of patients. They noted that chronic transfusion may simply delay episodes of ASSC to a later age and may not restore splenic function. In fact, Rogers et al. (11) reported that pitted red cell counts rose to asplenic levels after an episode of ASSC and rarely, if ever, returned to low values compatible with normal splenic pitting function.

Splenectomy. Powell et al. (8) described 12 patients with ASSC. One patient died, 3 patients with minor episodes were followed with no recurrences, and 8 patients had prompt splenectomy. They recommended splenectomy after the first major episode of ASSC and reasoned that removal of a poorly or non-functioning spleen does not add increased susceptibility to infections. Although chronic blood transfusion can delay splenectomy and temporarily restore splenic function, these advantages were thought to be outweighed by the risks of chronic blood product administration. In addition, Topley et al. (4) suggested that any child with a history of one (classical) episode of ASSC or a minor episode followed by the development of sustained hypersplenism, should undergo splenectomy.

More recently, in an analysis of 130 Jamaican patients with Hb SS treated by splenectomy (46 for recurrent ASSC), patients were compared with a control group matched for sex, age, and duration of followup in a retrospective review by Wright et al. (12). Mortality and bacteremic episodes did not differ between the splenectomy and control groups. Painful crises and acute chest syndrome were more common in the splenectomy group, but presumably, were not related to the splenectomy itself. The authors concluded that splenectomy does not increase the risk of death or bacteremic illness in patients with Hb SS and, if otherwise indicated, should not be deferred.

Partial splenectomy has been recommended for children with recurrent ASSC as a means of preventing further recurrence and retaining splenic function (13,14). However, one patient died of overwhelming sepsis despite using this approach (15).

Education. Emond et al. (3) described a parental education program in Jamaica aimed at early diagnosis of ASSC. The program, which involved more than 300 children with Hb SS, led to an increase in the incidence of ASSC from 4.6 to 11.3/100 patient-years, probably reflecting increased awareness of the complication. However, the mortality rate fell from 29.4/100 events to 3.1/100 events, a dramatic improvement resulting from improved medical management and earlier detection.


All reports regarding the management of ASSC (and chronic hypersplenism) were descriptive, retrospective, and uncontrolled. Thus, recommendations are based on Level of Evidence V. An important factor which may influence future decisions about splenectomy will be the widespread use of a protein-conjugated vaccine should prevent most serotypes of invasive Streptococcus pneumoniae beginning at a few months of age.

Our recommendations for the management of ASSC are:

  1. Early education should be provided to parents of infants with sickle cell disease regarding palpation of the spleen, symptoms of progressive anemia, and the appropriate action for obtaining rapid evaluation and treatment.
  2. Patients who have a life-threatening episode of ASSC which requires acute transfusion support should have a splenectomy shortly after the event.
  3. Alternatively, patients who have a severe episode of ASSC and are below age 2 years should be placed on a chronic transfusion program to keep Hb S levels below 30% until a splenectomy is performed at age 2 years.
  4. Patients with chronic hypersplenism also should have a splenectomy.

No prospective trials have been conducted but a randomized trial of the approaches described in recommendations (2) and (3) might be considered. The primary endpoint will be long-term morbidity and mortality from splenectomy versus transfusion. Unfortunately, such a trial probably would require a sample size far too large to attain even in a collaborative setting.



Because the life span of red blood cells is greatly shortened in sickle cell disease, temporary suppression of erythropoiesis can result in severe anemia. Such a transient aplastic crisis (TAC) typically is preceded by or associated with a febrile illness. The infectious nature of this problem is apparent from the fact that several members of families with congenital hemolytic anemia may have concurrent aplasia. Between 70 and 100% of episodes of TAC are due to infection by human parvovirus B19, also the cause of erythema infectiosum ("Fifth Disease") (16-18). Aplasia is the result of direct cytotoxicity of the parvovirus to erythroid precursors, although earlier progenitors may be affected in some conditions. Patients may present with increased fatigue, dyspnea, more severe anemia than usual, and a severe decrease in reticulocytes (usually <1%). Patients may have fever, signs of upper respiratory infection, and/or gastrointestinal symptoms at presentation, but skin rashes are characteristically absent. Reticulocytopenia begins at about 5 days post-exposure and continues for 7 to 10 days. Exacerbation of anemia develops shortly after reticulocytopenia. Hemoglobin levels reached a mean nadir of 3.9 g/dL in one series (19). Patients who present in the convalescent phase may be thought mistakenly to have a hyperhemolytic process because of severe anemia and high reticulocyte levels. The diagnosis may be confirmed by finding increased B19 parvovirus IgM levels. At least 20% of infections do not result in TAC (18). Following B19 infection, parvovirus-specific IgG concentrations are increased in most patients and protective immunity appears to be life-long; no cases of recurrent disease have been reported in children with sickle cell disease (18,20).

Although the majority of adults have acquired immunity to B19 parvovirus, hospital workers who are susceptible and are exposed to patients with TAC are at high risk of contracting nosocomial erythema infectiosum (21). Because infection during the mid-trimester of pregnancy may result in hydrops fetalis and stillbirth, isolation precautions for pregnant staff are a necessity if an aplastic crisis is suspected (22).


No experimental trials have been reported regarding the management of TAC. The primary treatment is supportive with packed red blood cell transfusions when necessary. Transfusion was required in 87% of children with Hb SS and TAC in a large Jamaican series (19), but is much less commonly needed for Hb SC disease. A single case report describes an alternative to transfusion in a child with Hb SD, whose mother was a Jehovahís Witness and refused transfusion (23). This patient was treated with a single dose of IV gammaglobulin (1 g/kg) and daily infusions of 100 units/kg of erythropoietin and exhibited a reticulocytosis beginning on day 4 after onset of this treatment. An important future development will be the availability of a vaccine against human parvovirus.

In the past decade, it has become apparent that a number of complications of B19 parvovirus infection besides TAC can occur in patients with sickle cell disease. These are summarized in the following table. Patients should be followed closely for these potential complications.
Complications Associated with Parvovirus B19 Infection in Patients with Sickle Cell Disease




of Patients



bone marrow necrosis, 











leukopenia 21%, neutropenia 27%, 

thrombocytopenia 42%

developed within 7 days in most; 

chronic course, 1 death

Hb SE disease, also had ACS









all Hb SS; proteinuria and 


Hb SS, chronic course

all Hb SS
acute chest syndrome
all Hb SC, 1 death
splenic sequestration
all Hb SS
hepatic sequestration

ACS = acute chest syndrome


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