In the past, the term hypersplenism or increased splenic function has been used to denote the syndrome characterized by splenic enlargement, deficiency of one or more blood cell lines, normal or hyperplastic cellularity of deficient cell lines in the marrow, and increased turnover of affected cells. Increased understanding of the pathophysiology of specific disorders has shown that hypersplenism is not synonymous with splenomegaly. Some disorders in which there is spleen-dependent destruction of blood elements do not manifest all features of hypersplenism. For example, splenomegaly is rarely a feature of thrombocytopenic purpura, and splenectomy is not always curative. Conversely, other conditions that enlarge the spleen may not result in destruction or sequestration of blood elements with resultant cytopenias. In disorders with known pathogenesis, the recent trend has been to classify them as separate disease entities rather than as hypersplenic conditions.
The defects in hypersplenism are exaggerations of normal splenic functions primarily associated with the red pulp. Etiologic factors include:
- neoplastic infiltration
- disease of the bone marrow in which the spleen becomes a site of extramedullary hematopoiesis
- metabolic disorders, genetic disorders such as Gaucher’s disease.
The hyperplastic spleen is not selective in its hyperfunction in most of these disorders. The splenomegaly can lead to an increased turnover in erythrocytes and platelets, with a lesser effect on leukocytes. For example, 60% of patients with cirrhosis develop splenomegaly and 15% develop hypersplenism. The hypersplenism of cirrhosis is seldom of clinical significance; the anemia and thrombocytopenia are usually mild and rarely are indications for splenectomy.
Symptoms and Signs
The clinical findings depend largely on the underlying disorder or are secondary to the depletion of circulating blood elements caused by the hypersplenism. Manifestations of hypersplenism usually develop gradually, and the diagnosis often follows a routine physical or laboratory examination. Some patients experience left upper quadrant fullness, discomfort (can be severe), or early satiety. Others have hematemesis due to gastroesophageal varices.
Disorders Associated with Secondary Hypersplenism.
- Congestive splenomegaly (cirrhosis, splenic vein obstruction)
- Neoplasm (leukemia, metastatic carcinoma)
- Inflammatory disease (sarcoid, lupus erythematosus, Felty’s syndrome)
- Acute infections with splenomegaly
- Chronic infection (tuberculosis, brucellosis, malaria)
- Storage diseases (Gaucher’s disease, Letterer-Siwe disease, amyloidosis)
- Chronic hemolytic diseases (spherocytosis, thalassemia, elliptocytosis)
- Myeloproliferative disorders
Purpura, bruising, and diffuse mucous membrane bleeding are unusual symptoms despite the presence of thrombocytopenia. Anemia may produce significant fatigue that may be the chief complaint in this population. Recurrent infections may be in patient with leukopenia.
Patients with primary hypersplenism usually exhibit pancytopenia of moderate degree and generalized marrow hyperplasia. Anemia is most prominent, reflecting the destruction of erythrocytes in the hypertrophied red pulp. Thrombocytopenia occurs due to sequestration of platelets but also possibly due to increased turnover. In most cases more immature cell types such as reticulocytes are present, reflecting the overactivity of the bone marrow to compensate for the pancytopenias. One exception is myeloid metaplasia, in which dysfunction of the bone marrow.
Evaluation of Splenic Size
Before it becomes palpable, an enlarged spleen may cause dullness to percussion above the left costal margin. Splenomegaly is manifested on supine x-rays of the abdomen by medial displacement of the stomach and downward displacement of the transverse colon and splenic flexure. CT scan is useful for differentiating the spleen from other abdominal masses and for demonstrating splenic enlargement or intrasplenic lesions. Some of the largest massive spleens (spleen weight > 1500 g) occur in these types of disease. Finding the edge of the spleen below the iliac crest and crossing the abdominal midline are frequently seen.
Leukemia and lymphoma are diagnosed by marrow aspiration, lymph node biopsy, examination of the blood (white count and differential). In hereditary spherocytosis there are spherocytes, osmotic fragility is increased, and platelets and white cells are normal. The hemoglobinopathies with splenomegaly are differentiated on the basis of hemoglobin electrophoresis, the demonstration of an unstable hemoglobin level. Thalassemia major becomes apparent in early childhood, the blood smear morphology is characteristic. In myelofibrosis, the bone marrow shows proliferation of fibroblasts and replacement of normal elements. In idiopathic thrombocytopenic purpura, the spleen is normal. In aplastic anemia, the spleen is not enlarged and the marrow is fatty.
Treatment of Hypersplenism
The course, response to treatment, prognosis of the hypersplenic syndromes differ widely depending on the underlying disease and its response to treatment.
Indications for Splenectomy
Splenectomy always indicated
- Primary tumor (rare)
- Hereditary spherocytosis (congenital hemolytic anemia)
Splenectomy usually indicated
Splenectomy sometimes indicated
- Elliptocytosis with hemolysis
- Nonspherocytic congenital hemolytic anemias
- Hodgkin’s disease (for staging)
- Idiopathic myelofibrosis
- Splenic artery aneurysm
- Wiskott-Aldrich syndrome
- Gaucher’s disease
- Mastocytosis-aggressive disease
Splenectomy rarely indicated
- Chronic leukemia
- Splenic lymphoma
- Thalassemia major
- Sickle cell anemia
- Felty’s syndrome
- Hairy cell leukemia
- Chédiak-Higashi syndrome
Splenectomy not indicated
- Hereditary hemolytic anemia of moderate degree
- Acute leukemia
Splenectomy may decrease transfusion requirements, decrease the incidence and number of infections, prevent hemorrhage, and reduce pain. The course of congestive splenomegaly due to portal hypertension depends upon the degree of venous obstruction and liver damage. The hypersplenism is rarely a major problem and is almost always overshadowed by variceal bleeding or liver dysfunction.