Acute splenic sequestration crisis resembling sepsis in an adult with hemoglobin SC disease.

Abstract: Acute splenic sequestration crisis (ASSC) is a common complication of sickle cell anemia in children. ASSC is generally not seen in adults with the SS genotype but occasionally can be seen in adults with the SC genotype. We present a case of fulminant ASSC in an adult with hemoglobin SC who developed high fever, intense abdominal pain, leukocytosis, and jaundice.

Key Words: acute splenic sequestration crisis, adults, sickle cell anemia

**********

Acute splenic sequestration crisis (ASSC) is a life-threatening complication of sickle cell anemia that results when intrasplenic sickling prevents blood from leaving the spleen and acute splenic engorgement ensues. In patients with the hemoglobin SS genotype, ASSC is a pediatric disease: functional asplenia results from recurrent splenic infarctions in childhood, and by adulthood, there is little distensible splenic tissue remaining. (1) In contrast, recurrent splenic infarction is less common in patients with the SC and sicklethalassemia genotypes, and splenomegaly often persists into adulthood. (2,3) In these patients, distensible splenic tissue provides the substrate for sequestration crises later in life.

Clinically, ASSC is characterized by a precipitous drop in hemoglobin concentration, tender splenomegaly, thrombocytopenia, and reticulocytosis. (4) Effective circulating blood volume is reduced, sometimes leading to hemodynamic instability. Fever, leukocytosis, splenic rupture, and death may occur. (5) Mortality has been estimated at 15%. (6) We present a case of ASSC in an adult with sickle cell anemia who suddenly developed tender splenomegaly, high fever, acute anemia, thrombocytopenia, leukocytosis, jaundice, hypoxia, and tachycardia. He was thought to have sepsis, but this diagnosis was ruled out after microbiologic evaluation and invasive testing.

Case Report

A 36-year-old black male with a history of hemoglobin SC disease presented with severe left hip pain. He had been hospitalized multiple times previously for complications of his sickle-cell disease including pneumonia, cholecystitis, and avascular necrosis of both femoral heads. He had known splenomegaly with splenic infarctions by prior computed tomographic (CT) scanning and had mild chronic thrombocytopenia (platelets, 94,000-128,000/[micro]L), suggesting hypersplenism.

Physical examination at admission was remarkable only for limited range of motion of the left hip secondary to pain. Admission laboratory testing showed no evidence of hemolysis or infection; hemoglobin, reticulocyte count, bilirubin, lactate dehydrogenase, and white blood cell count were all normal (Table 1). Intravenous fluid and analgesics were administered.

On hospital day 5, he began to experience intense left upper quadrant pain. He became febrile to 40.3[degrees]C, with associated tachypnea (respiratory rate, 24 breaths/min), tachycardia (heart rate, 130 beats/min), diaphoresis, hypoxia, and jaundice. His abdomen was diffusely distended, and intense left upper quadrant tenderness precluded the identification of the spleen tip. His hemoglobin decreased from 13.5 g/dL to 7.5 g/dL. His reticulocyte count increased to 4.2%, his lactate dehydrogenase was 1,387 U/[micro]L, and his bilirubin was 13.7 mg/dL. The white cell count increased to 37,000/[micro]L and platelets fell to 65,000/[micro]L (Table 1). The P[O.sub.2] was 41 mm Hg on room air. He received three units of packed red blood cells and was started on broad-spectrum antibiotics after blood cultures were drawn.

Chest radiography showed bibasilar atelectasis and a small left pleural effusion. CT scan of the abdomen showed marked splenomegaly and a mass-like process in the inferior aspect of the spleen (Fig. 1). This lesion had not been present on prior CT scans of the abdomen and did not appear to be a splenic infarction based on its density and regional mass effect; on the basis of discussion with the attending radiologist, it was thought that this lesion likely represented a tumor or an evolving abscess. Needle aspiration of the splenic lesion was negative for malignant cells, and cultures were negative for bacteria, fungus, and mycobacteria. Blood cultures, urine cultures, human immunodeficiency virus antibody, cytomegalovirus cultures, and purified protein derivative were also negative. Pleural fluid was exudative but there were no organisms present.

With supportive care, the patient gradually improved. His clinical deterioration was attributed to an ASSC, and he was rehospitalized the next month for an elective laparoscopic splenectomy. Pathologic examination of the spleen was consistent with ASSC: the spleen weighed 900 g (the average adult spleen weighs 150 g), (7) and histologic examination revealed multiple areas of infarction. Viable areas showed marked splenic congestion with sickled red cells (Fig. 2) and multiple areas of infarction but no evidence of infection or tumor.

Discussion

ASSC is a common complication of sickle cell anemia in children with the SS genotype. It is less common in patients with the SC genotype. In one large series of children with hemoglobin SC disease, only 5% had episodes of acute splenic sequestration. (8) ASSC is even rarer in adults; when it does occur, it is often in the setting of low ambient oxygen tension, as occurs at high altitudes. (5,9)

Treatment of the acute crisis involves transfusion of blood products and supportive care with intravenous fluids, oxygen, and pain control. Given the potential for mortality, and because sequestration recurs in the majority of cases, (3,10) splenectomy is generally recommended after the acute event remits, (3,6,10) provided that the patient is an appropriate surgical candidate. Pathologic examination of the spleen during ASSC reveals marked splenomegaly, with weights reported up to 1,870 g. (4) Microscopic examination shows extensive pooling of red blood cells within the splenic cords, many of which are sickled. Numerous areas of necrosis and infarction may also be identified. (4)

[FIGURE 1 OMITTED]

Diagnosis is made on the basis of the clinical presentation. Scanning with [.sup.99m]Tc/sulfur colloid during the sequestration crisis classically shows almost complete lack of splenic uptake. CT scan may reveal multiple, peripheral, nonenhancing, low-density areas or large, diffuse areas of low density in the majority of the splenic tissue. (11) Although splenic infarcts may be apparent radiographically, marked splenomegaly, decreasing hemoglobin, hemodynamic instability, and multiorgan failure should alert the clinician to the possibility of splenic sequestration. Needle biopsy is not indicated to confirm the diagnosis of ASSC and should be discouraged, given the theoretical risk of splenic rupture. Fortunately, our patient did not suffer adverse consequences from this unnecessary diagnostic procedure.

Conclusion

This case illustrates the fulminant course of ASSC. The marked inflammatory response and hemodynamic instability resulting from this condition may mimic sepsis, but the presence of left upper quadrant pain, tender splenomegaly, and a rapid decrease in hemoglobin should alert the clinician to the possibility of ASSC. Early recognition allows for prompt intervention and may prevent excessive diagnostic and therapeutic procedures.

[FIGURE 2 OMITTED]

Table 1. Laboratory studies during hospitalization (a)

                         Admission  Decompensation  Discharge
                          (Day 0)     (Days 5-7)     (Day 13)

Serum electrolytes       Normal     Normal          Normal
Serum bicarbonate            25         26               29
Serum blood
  urea nitrogen              12         13                8
Serum creatinine              0.8        1.3              0.7
AST                                     90
ALT                                     18
Alkaline phosphatase                    75
Total bilirubin               1.2       13.7              4.5
Conjugated bilirubin                     2.8
Lactate dehydrogenase       157      1,387            1,390
White blood cell count
  (cells/[micro]l)        8,490     36,980           13,380
Hemoglobin (g/dl)            13.5        7.5              9.3 (b)
Platelets
  (cells/[micro]l)      117,000     65,000          525,000

(a) AST, aspartate aminotransferase: ALT, alanine aminotransferase.
(b) After transfusion of three units packed red blood cells.

Accepted April 30, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0413

References

1. Orringer EP, Fowler VG Jr, Owens CM, et al. Case report: splenic infarction and acute splenic sequestration in adults with hemoglobin SC disease. Am J Med Sci 1991;302:374-379.

2. Koduri PR, Agbemadzo B, Nathan S. Hemoglobin SC disease revisited: clinical study of 106 adults. Am J Hematol 2001;68:298-300.

3. Solanki DL, Kletter GG, Castro O. Acute splenic sequestration crises in adults with sickle cell disease. Am J Med 1986;80:985-990.

4. Sears DA, Udden MM. Splenic infarction, splenic sequestration, and functional hyposplenism in hemoglobin SC disease. Am J Hematol 1985;18:261-268.

5. Shao SH, Orringer EP. Case report: splenic sequestration and multiorgan failure as the presenting manifestation of hemoglobin SC disease. Am J Med Sci 1996;311:139-141.

6. Embury S, Vichinsky E. Sickle cell disease, in Silberstein L, McGlave P (eds): Hematology: Basic Principles and Practice. New York, Churchill Livingstone, 2000, pp 523-524.

7. Bannister L. Haemolymphoid system, in Bannister L (ed): Gray's Anatomy. New York, Churchill Livingstone, 1995, ed 38, pp 1399-1442.

8. Aquino VM, Norvell JM, Buchanan GR. Acute splenic complications in children with sickle cell-hemoglobin C disease. J Pediatr 1997;130:961-965.

9. Michel JB, Hernandez JA, Buchanan GR. A fatal case of acute splenic sequestration in a 53-year-old woman with sickle-hemoglobin C disease. Am J Med 1992;92:97-100.

10. Grover R, Wethers DL. Management of acute splenic sequestration crisis in sickle cell disease. J Assoc Acad Minor Phys 1990;1:67-70.

11. Sheth S, Ruzal-Shapiro C, Piomelli S, et al. CT imaging of splenic sequestration in sickle cell disease. Pediatr Radiol 2000;30:830-833.

RELATED ARTICLE: Key Points

* Adults with the hemoglobin SC genotype, unlike those with the SS genotype, occasionally develop acute splenic congestion with associated left upper quadrant pain, fever, splenomegaly, jaundice, and acute anemia.

* Noninfectious splenic processes such as acute splenic sequestration crisis can be associated with signs and symptoms resembling sepsis, such as high fever, hemodynamic instability, and profound leukocytosis.

* Acute splenic sequestration crisis should be differentiated from splenic infarction because acute splenic sequestration crisis is more life threatening, and surgical management may be indicated.

Andrea Wang-Gillam, MD, PHD, Rita Shi-Ming Lee, MD, Eric D. Hsi, MD, and Daniel J. Brotman, MD

From the Departments of Internal Medicine, Clinical Pathology, and General Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH. Dr. Wang-Gillam is currently at the Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR.

Reprint requests to Daniel J. Brotman, MD, Department of General Internal Medicine (S70), Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Email: [e-mail]