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CHAPTER 56 platelet count. The presence of pitted red cells identified by interference-

HYPERSPLENISM AND contrast microscopy is perhaps the most specific blood finding of hyposplenism,
followed by Howell-Jolly bodies. The most devastating consequence of hypo-
HYPOSPLENISM splenism is sudden overwhelming sepsis by encapsulated bacteria. Immu-
nizations and prophylactic antibiotics can decrease the risk of sepsis. A high
awareness and prompt antibiotic treatment of febrile episodes are warranted.

Jaime Caro and Srikanth Nagalla

HYPERSPLENISM
SUMMARY
HISTORY
The spleen culls aged and abnormal cells from the blood; removes intraery- The spleen has intrigued physicians and philosophers since ancient
throcytic inclusions through a process called pitting; sequesters approxi- times and has been assigned mysterious powers, but its association with
1
mately one-third of the normal intravascular platelet pool; removes bacteria, destruction of blood cells was not elucidated until the turn of the 20th
foreign particles, and tumor cells from the blood; and by virtue of the T and century. The exaggerated and unfounded worry about somatic com-
B lymphocytes and macrophages in the white pulp, plays a role in immune sur- plaints often reflected by the sense of pain in the spleen (left hypochon-
veillance and antibody formation. Splenomegaly can occur as a result of vas- drium) led to the term hypochondriac. In 1899, Chauffard proposed that
cular engorgement or cellular infiltration, and it is frequently associated with a increased splenic activity causes hemolysis. This proposal provided the
2
combination of neutropenia, thrombocytopenia, and anemia. Hypersplenism impetus for therapeutic splenectomy, which was performed first in 1910
3
is defined as one or more blood cytopenias in the setting of splenomegaly. by Sutherland and Burghard in a patient with splenic anemia (hered-
4
Hypersplenism can occur with moderate or minimal splenic enlargement as itary spherocytosis) and subsequently by Kaznelson in a patient with
a result of exaggerated removal of physically abnormal (e.g., as in hereditary essential thrombocytopenia (immune thrombocytopenic purpura)
spherocytosis) or antibody-coated blood cells (e.g., as in autoimmune hemo- in 1916.
lytic anemia). The presence of splenomegaly in a patient with blood cytope-
nias is useful to narrow the cause of the cytopenias, although the cause of the DEFINITION
blood cytopenias may not be solely or principally as a result of hypersplenism Hypersplenism is defined as blood cytopenias in the setting of
(e.g., as in hairy cell leukemia). Thrombocytopenia in the setting of cirrhosis splenomegaly. This is usually accompanied by hyperplasia of the affected
and splenomegaly is the result of pooling in the enlarged spleen and a relative cell precursors in the marrow. There can be a disproportional decrease
decrease in thrombopoietin. The role of the spleen in the anemia and neutro- in the blood platelets, white cells, and red cells, with thrombocytope-
penia associated with cirrhosis with splenomegaly is poorly understood, but nia and leukopenia being disproportionate to the anemia as a result of
a relative reduction in erythropoietin levels and decreased marrow myeloid hypersplenism. Splenomegaly can occur as a result of elevated splenic
venous pressures and vascular congestion, histiophagocytic hyperpla-
progenitor cells have been proposed. Splenectomy has been used in cases of sia, other cellular infiltration, or because of the inability of physically
severe thrombocytopenia requiring chronic platelet transfusions or leading to abnormal red cells, such as sickle cells in infants and children (prior to
bleeding. Thrombopoietin receptor agonists are another option in the manage- infarction atrophy), or antibody-coated cells, such as in autoimmune
ment of thrombocytopenia, and nonpeptide thrombopoietin receptor agonists hemolytic anemia, to navigate the circulation or avoid engulfment by
have been shown to increase platelet counts in patients with thrombocy- the mononuclear phagocyte population of the normal spleen. The blood
5
topenia associated with hepatitis C virus–related cirrhosis and splenomegaly. cytopenias are not generally corrected by relief of portal hypertension. 6,7
Splenectomy may be justified in the case of massive splenomegaly, infarction,
or disabling symptoms of pain and compression of neighboring structures. In ONTOGENY
some circumstances, benefit can be achieved by partial destruction of splenic The embryonic spleen appears in the first trimester of gestation as a
tissue by embolization using intraarterial infusion of gel microparticles. Hypo- multiply lobulated condensation of highly vascular mesenchymal cell
splenism can result from agenesis, atrophy, surgical removal of the spleen, aggregates interposed in the arterial circulation in the dorsal mesogas-
or reduction of splenic function by disease. In the latter case, disturbance in trium. The full scope of the molecular basis of splenic organogenesis is
splenic circulation disrupts the specific architecture required for the spleen’s not known. The HOX11 and WT1 genes are essential for its formation,
culling, phagocytic, and pitting functions. Hyposplenism may be suspected and defects in their expression result in hyposplenia or asplenia. 8–10
by alterations in red cell morphology, such as target cells or acanthocytes; red The lymphoid compartment, the white pulp, begins its develop-
cell inclusions, specifically Howell-Jolly and Pappenheimer bodies (siderotic ment early in the second trimester of gestation, when mature T cells,
granules highlighted with polychrome stains); pitted red cells; or an elevated principally CD4+ lymphocytes, form a continuous layer along the length
of the vessels (periarteriolar sheaths). CD8+ cells reside in splenic cords
and a specialized subset of γδT cells home to the pulp (Chap. 6). Immu-
noglobulin (Ig) D+ and IgG+ B lymphocytes form localized deposits,
the primary lymph follicles. Secondary follicles arise later in life, after
Acronyms and Abbreviations: G-CSF, granulocyte colony-stimulating factor; exposure to immunologic stimuli, and have a distinctive structure that
Ig, immunoglobulin; TPO-RA, thrombopoietin-receptor agonist. includes a germinal center, a mantle zone, and a marginal zone contain-
ing IgM+ and IgG+ B lymphocytes. 11,12

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