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 CRISIS (ASSC)

Introduction

Methods

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.
 

Recommendations

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.
 

TRANSIENT APLASTIC CRISIS (TAC)

Background

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).
 

Management

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

Complication	Reference	Number of Patients	Age (years)	Comments
bone marrow necrosis,  pancytopenia	24     25     26	46     2     1	1.5-14     18,20     22	leukopenia 21%, neutropenia 27%,  thrombocytopenia 42% developed within 7 days in most;  chronic course, 1 death Hb SE disease, also had ACS
glomerulonephritis	27     28	7     1	8-29     13	all Hb SS; proteinuria and  nephrotic  Hb SS, chronic course
stroke	29	3	3,3,6	all Hb SS
acute chest syndrome	30	3	21,22,27	all Hb SC, 1 death
splenic sequestration	31	3	1.8,8,10	all Hb SS
hepatic sequestration	32	1	22	Hb SS

ACS = acute chest syndrome
 

References