MANAGEMENT AND THERAPY OF SICKLE CELL DISEASE

NIH Publication No. 95-2117, Revised December 1995 (Third Edition) National Institutes of Health, National Heart, Lung, and Blood Institute

Chapter 11--Splenic Sequestration and Transient Aplastic Crisis

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" in the United States are splenic sequestration and erythroid aplasia.

SPLENIC SEQUESTRATION

Much of the severe morbidity and mortality of sickle cell anemia in the first few years of life is a consequence of the so-called acute splenic sequestration crisis. This was first described in 1945 in a review of 11 fatal cases of sickle cell anemia where death was caused by "abdominal crises." These catastrophic events were characterized by severe anemia, splenomegaly, hypovolemic shock, and sudden death, and it was suggested that patients had literally "bled into their spleens." Infants and young children with sickle cell anemia whose spleens have not yet undergone multiple infarctions and subsequent fibrosis, and those individuals with other forms of sickle cell disease whose spleens remain enlarged into adult life, can suddenly have intrasplenic pooling of vast amounts of blood. In SS disease, these events can occur as early as 2 months of age and are unusual after age 3 years. They are often associated with viral or bacterial infections.

During severe splenic sequestration, the spleen becomes enormous, filling the abdomen and even reaching into the pelvis. The usual clinical manifestations of this complication are sudden weakness, pallor of the lips and mucous membranes, tachycardia, tachypnea, and abdominal fullness. Anemia can be profound, thrombocytopenia due to splenic entrapment is common, and the reticulocyte count is often markedly elevated. Splenic sequestration is one of the most dangerous events in the life of a patient with sickle cell anemia and must be promptly recognized and treated. Within hours of the first signs of this disturbance, hypovolemic shock and death can occur. With increasing numbers of children diagnosed at birth with sickle cell disease and carefully followed thereafter, it has become apparent that minor (or "subacute") episodes of splenic sequestration are common. These episodes are characterized by a moderate increase in spleen size associated with a fall in baseline hemoglobin level of 2 to 3 g/dL. The reticulocyte count may increase above usual levels.

These episodes may resolve spontaneously or splenomegaly may persist; management consists of careful surveillance. Some patients may ultimately require splenectomy if significant cytopenias occur. Early diagnosis of sickle cell disease permits training of parents to palpate their infants' abdomens to determine the size of the spleen (see Chapter 1). Parents must be instructed to seek immediate medical attention if they notice increased pallor, abdominal pain or enlargement, or rapid splenic enlargement. Educating parents is an essential component of newborn screening followup and has resulted in reduced mortality from splenic sequestration.

Splenic sequestration crises can occur in older patients with Hb SC disease and S beta + thal whose spleens either remain enlarged or retain the capability to enlarge. Although these episodes are often mild, are associated with decreased hemoglobin levels of 2 to 3 g/dL, and rarely require supportive transfusions, severe and fatal sequestration has occurred in some patients. In children or adults with splenomegaly (usually patients with Hb SC disease or Hb S beta + thal), acute splenic infarction may occur, causing severe left upper quadrant pain that is sometimes accompanied by a "splenic friction rub" audible when the patient inspires. The infarcts may be visualized by CT or MRI scans. Although these episodes often resolve with conservative management, intractable pain may necessitate splenectomy.

Treatment of the acute splenic sequestration is directed toward the prompt correction of hypovolemia with plasma expanders followed by red blood cell transfusion as they become available. A dramatic regression of splenomegaly and rise in hemoglobin level can occur in a short time after transfusion. Because of this phenomenon, the goal of transfusion should be to restore intravascular volume and achieve a posttransfusion hemoglobin level of 6-8 g/dL; although transfusion is usually required, care should be taken not to overtransfuse. Because severe splenic sequestration can result in fatality within a few hours and because of its tendency to recur, splenectomy should be strongly considered if a child has had two or more of these episodes; some would recommend splenectomy after a single severe episode. Because the spleen in SS disease is frequently dysfunctional after 6 to 9 months of age, the risk of postsplenectomy infection is probably not greatly increased. Alternatively, a program of chronic transfusion can be used in infants younger than age 2 years, the age at which immunization with the pneumococcal vaccine is more effective. Chronic transfusion therapy usually reduces spleen size, restores function, and prevents sequestration, thus avoiding splenectomy in the very young child. When transfusions are discontinued, however, the child may again be at risk for sequestration.

Educating parents about splenic palpation is particularly important after the child has had an initial episode. Some patients with sickle cell disease develop chronic massive splenomegaly with associated hypersplenism. Splenectomy is indicated when the degree of anemia, neutropenia, or thrombocytopenia is severe, or when pain or discomfort is associated with the enlarged spleen.

TRANSIENT APLASTIC CRISES

Because the red blood cell lifespan is shortened in sickle cell disease, even transient suppression of erythropoiesis can result in severe anemia; these episodes are called transient aplastic crises. The large majority of episodes of severe reticulocytopenia are due to infection by parvovirus B-19, also the cause of erythema infectiosum ("fifth disease"). Patients may present with increased fatigue, dyspnea, more severe anemia than usual, and few or no reticulocytes. The anemia is often well-compensated, with minimal elevation of pulse or respiratory rate. Although fever and signs of upper respiratory infection may be present, skin rash is characteristically absent. Concurrent acute chest syndrome may occur. Confirmation of acute parvovirus B-19 infection is possible by a variety of serological and microbiological techniques. Erythroid aplasia terminates spontaneously after 5 to 10 days; leuko- erythroblastosis is common in the peripheral blood during recovery. Patients who present in the convalescent phase may be mistakenly assumed to have hyperhemolysis because of severe anemia and high reticulocyte levels. Treatment for transient aplastic crisis is supportive. Packed red blood cell transfusions are often necessary in those with SS disease and S beta o thal because of tachycardia and tachypnea. Transfusions are required less frequently in those with other forms of sickle cell disease. If the patient can be relied on to return for frequent checkups or seek medical help if symptoms worsen, prolonged hospitalization is usually not required.

In addition to erythema infectiosum, parvovirus B-19 has been associated with hydrops fetalis secondary to intrauterine infection and chronic viremia with anemia or pancytopenia in patients with immunodeficiency. Respiratory isolation of patients with transient aplastic crisis should be implemented to prevent exposure of other patients with sickle cell disease, patients with immunodeficiency (e.g., congenital, HIV-related, or chemotherapy-induced), and pregnant females (i.e., nursing staff). Patients should be considered infectious until reticulocytosis occurs. A marked decrease in the reticulocyte count below what is usual for a given patient can herald aplastic crisis. Therefore, the evaluation of the febrile patient should include measurement of the reticulocyte count; a low reticulocyte count mandates further monitoring of the hemoglobin level. Various viral and bacterial infections can cause transient and less severe hypoplasia. Particularly in adolescents and adults, urinary tract or pulmonary infections, as well as severe and protracted painful crises, should be considered causes of reticulocytopenia.

BIBLIOGRAPHY

Emond AM, Collis R, Darvill D, et al. Acute splenic sequestration in homozygous sickle cell disease: natural history and management. J Pediatr 1985;107:201.

Kinney TR, Ware RE, Schultz WH, et al. Long-term management of splenic sequestration in children with sickle cell disease. J Pediatr 1990;117:194.

Pattison JR, Jones SE, Hodgson J, et al. Parvovirus infections and hypoplastic crises in sickle cell anemia. Lancet 1981;1:644.

Seeler RA, Shwiaki MZ. Acute splenic sequestration crises in young children with sickle cell anemia. Clin Pediatr 1972;11:701.

Serjeant GR, Serjeant BE, Thomas PW, et al. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993;341:1237-40.

Topley AM, Rogers DW, Stevens MCG, et al. Acute splenic sequestration and hypersplenism in the first five years in homozygous sickle cell disease. Arch Dis Child 1981;56:765.

Send mail to aplatt@emory.edu with questions or comments about this web site.
Copyright © 1997 Sickle Cell Information Center
Last modified: September 07, 1997