Sickle Cell Disease

CASE CONTINUED

Two months later, the patient presents again to the emergency department with the same complaint of leg pain, as well as abdominal pain. His hemoglobin is 12.5 g/dL, and his platelet count is 134,000/µL. His pain is not improved with 3 doses of morphine 6 mg intravenously, and he is admitted to the medicine service. A hemoglobin profile is obtained, revealing 52% HbS, 45% HbC, and 1.5% HbF, consistent with HbSC. In sickle cell trait, the hemoglobin profile is 60% HbA and 40% HbS (available α-globin prefers to pair with a normal β-globin, so the ratio of HbA to HbS is 60:40, not 50:50).

On the second hospital day, the patient’s hemoglobin drops to 7.2 g/dL and his platelet count decreases to 44,000/µL. His abdomen is distended and diffusely tender. The internist transfuses him with 2 units of packed red blood cells (PRBC), after which his hemoglobin increases to 11 g/dL, while his platelet count increases to 112,000/µL. Following the transfusion, his abdominal pain resolves, as does his anemia and thrombocytopenia.

• What caused this patient’s anemia and thrombocytopenia?

High on the differential diagnosis is a splenic sequestration. Acute splenic sequestration occurs when red cells are trapped in the splenic sinuses. Massive splenic enlargement may occur over several hours.^89,90 Unrecognized splenic sequestration has a high mortality rate from severe anemia and splenic rupture.⁹⁰ Splenic sequestration must be ruled out in a sickle cell patient with abdominal pain accompanied by dropping platelet and red cell counts, especially in milder subtypes that often have splenic function preserved into adolescence and adulthood. Sickle cell anemia patients usually become functionally asplenic in early childhood.^89,91,92 The rise in hemoglobin, more than would be expected from 2 units of PRBC, plus the improvement in platelet count without a platelet transfusion observed in the case patient strongly supports the diagnosis of splenic sequestration.

Splenic sequestration can occur in any sickle cell patient whose spleen has not fibrosed. Splenic sequestration in adulthood is not uncommon in HbSC patients, who often have preserved splenic function into adulthood.^93–95

Clinical signs of splenic sequestration include a rapid drop in hemoglobin, rise in reticulocyte count, a tender, enlarged spleen, and, in severe cases, hypovolemia.^89,93 It is treated with prompt blood transfusion, but care must be taken not to overtransfuse the patient, as the spleen can trap several grams of hemoglobin, which may be released upon transfusion, potentially causing life-threatening hyperviscosity.⁸⁹ Hemoglobin levels must be checked following transfusion in suspected splenic sequestration, and “mini transfusions” of 5 mL/kg are recommended in sickle cell disease patients who are hemodynamically stable.²⁰

Hepatic sequestration may also occur, but it is much less common than splenic sequestration.⁹⁶ Other conditions on the differential diagnosis include thrombotic thrombocytopenic purpura, which would be unlikely to respond to a transfusion. ACS can cause a drop in hemoglobin, and is treated with simple or exchange transfusions.⁹⁷ ACS is less likely without respiratory symptoms or oxygen requirement, and usually is not associated with thrombocytopenia. Sepsis may also cause anemia and thrombocytopenia, but again would not likely respond to a simple transfusion. The patient’s response to transfusion is consistent with a sequestering event, not a destructive event as in the case of sepsis.

CASE CONTINUED

Imaging reveals a grossly enlarged spleen, which is having a mass effect on the left kidney. The patient is started on hydroxyurea therapy at 500 mg 3 times daily. Discharge instructions include following up with his primary care physician, continuing hydroxyurea therapy, and receiving yearly dilated eye exams to evaluate for proliferative sickle retinopathy.

• Are these discharge instructions complete?

Splenic sequestration has a 50% recurrence rate.⁹⁸ In very young children, watchful waiting or chronic transfusion may be implemented to preserve the immunologic function of the spleen and reduce the risk of sepsis.⁸⁹ Splenectomy after a single episode of sequestration in adults is a matter of debate, with experts advising both watchful waiting⁹⁹ and splenectomy after recovery from the first sequestering event.¹⁰⁰ The patient should have been informed of the risk for recurrence, and the signs and symptoms of splenic sequestration as well as the need for emergency medical attention should have been discussed. Splenic sequestration may be milder in adults than in children, but fatal sequestrations have been reported.^95,101–103