Chapter 56: Hypersplenism and Hyposplenism

Jaime Caro; Srikanth Nagalla

INTRODUCTION

SUMMARY

The spleen culls aged and abnormal cells from the blood; removes intraerythrocytic inclusions through a process called pitting; sequesters approximately one-third of the normal intravascular platelet pool; removes bacteria, foreign particles, and tumor cells from the blood; and by virtue of the T and B lymphocytes and macrophages in the white pulp, plays a role in immune surveillance and antibody formation. Splenomegaly can occur as a result of vascular engorgement or cellular infiltration, and it is frequently associated with a combination of neutropenia, thrombocytopenia, and anemia. Hypersplenism is defined as one or more blood cytopenias in the setting of splenomegaly. Hypersplenism can occur with moderate or minimal splenic enlargement as a result of exaggerated removal of physically abnormal (e.g., as in hereditary spherocytosis) or antibody-coated blood cells (e.g., as in autoimmune hemolytic anemia). The presence of splenomegaly in a patient with blood cytopenias is useful to narrow the cause of the cytopenias, although the cause of the blood cytopenias may not be solely or principally as a result of hypersplenism (e.g., as in hairy cell leukemia). Thrombocytopenia in the setting of cirrhosis and splenomegaly is the result of pooling in the enlarged spleen and a relative decrease in thrombopoietin. The role of the spleen in the anemia and neutropenia associated with cirrhosis with splenomegaly is poorly understood, but a relative reduction in erythropoietin levels and decreased marrow myeloid progenitor cells have been proposed. Splenectomy has been used in cases of severe thrombocytopenia requiring chronic platelet transfusions or leading to bleeding. Thrombopoietin receptor agonists are another option in the management of thrombocytopenia, and nonpeptide thrombopoietin receptor agonists have been shown to increase platelet counts in patients with thrombocytopenia associated with hepatitis C virus–related cirrhosis and splenomegaly. Splenectomy may be justified in the case of massive splenomegaly, infarction, or disabling symptoms of pain and compression of neighboring structures. In some circumstances, benefit can be achieved by partial destruction of splenic tissue by embolization using intraarterial infusion of gel microparticles. Hyposplenism can result from agenesis, atrophy, surgical removal of the spleen, or reduction of splenic function by disease. In the latter case, disturbance in splenic circulation disrupts the specific architecture required for the spleen’s culling, phagocytic, and pitting functions. Hyposplenism may be suspected by alterations in red cell morphology, such as target cells or acanthocytes; red cell inclusions, specifically Howell-Jolly and Pappenheimer bodies (siderotic granules highlighted with polychrome stains); pitted red cells; or an elevated platelet count. The presence of pitted red cells identified by interference-contrast microscopy is perhaps the most specific blood finding of hyposplenism, followed by Howell-Jolly bodies. The most devastating consequence of hyposplenism is sudden overwhelming sepsis by encapsulated bacteria. Immunizations and prophylactic antibiotics can decrease the risk of sepsis. A high awareness and prompt antibiotic treatment of febrile episodes are warranted.

Acronyms and Abbreviations:

G-CSF, granulocyte colony-stimulating factor; Ig, immunoglobulin; TPO-RA, thrombopoietin-receptor agonist.

HYPERSPLENISM

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HISTORY

The spleen has intrigued physicians and philosophers since ancient times¹ and has been assigned mysterious powers, but its association with destruction of blood cells was not elucidated until the turn of the 20th century. The exaggerated and unfounded worry about somatic complaints often reflected by the sense of pain in the spleen (left hypochondrium) led to the term hypochondriac. In 1899, Chauffard proposed that increased splenic activity causes hemolysis.² This proposal provided the impetus for therapeutic splenectomy, which was performed first in 1910 by Sutherland and Burghard³ in a patient with splenic anemia (hereditary spherocytosis) and subsequently by Kaznelson⁴ in a patient with essential thrombocytopenia (immune thrombocytopenic purpura) in 1916.

DEFINITION

Hypersplenism is defined as blood cytopenias in the setting of splenomegaly. This is usually accompanied by hyperplasia of the affected cell precursors in the marrow. There can be a disproportional decrease in the blood platelets, white cells, and red cells, with thrombocytopenia and leukopenia being disproportionate to the anemia as a result of hypersplenism. Splenomegaly can occur as a result of elevated splenic venous pressures and vascular congestion, histiophagocytic hyperplasia, other cellular infiltration, or because of the inability of physically abnormal red cells, such as sickle cells in infants and children (prior to infarction atrophy), or antibody-coated cells, such as in autoimmune hemolytic anemia, to navigate the circulation or avoid engulfment by the mononuclear phagocyte population of the normal spleen.⁵ The blood cytopenias are not generally corrected by relief of portal hypertension.^6,7

ONTOGENY

The embryonic spleen appears in the first trimester of gestation as a multiply lobulated condensation of highly vascular mesenchymal cell aggregates interposed in the arterial circulation in the dorsal mesogastrium. The full scope of the molecular basis of splenic organogenesis is not known. The HOX11 and WT1 genes are essential for its formation, and defects in their expression result in hyposplenia or asplenia.^8,9,10

The lymphoid compartment, the white pulp, begins its development early in the second trimester of gestation, when mature T cells, 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). Immunoglobulin (Ig) D+ and IgG+ B lymphocytes form localized deposits, the primary lymph follicles. Secondary follicles arise later in life, after exposure to immunologic stimuli, and have a distinctive structure that includes a germinal center, a mantle zone, and a marginal zone containing IgM+ and IgG+ B lymphocytes.^11,12

STRUCTURE AND FUNCTIONAL ORGANIZATION

The normal adult spleen weighs 135 ± 30 g and has a blood flow that is approximately 5 percent of the cardiac output. In addition to serving as a filter, the spleen plays a role in innate and adaptive immunity and protection against microbes. The spleen is composed of white pulp, a marginal zone, and red pulp. The spleen’s principal structure is organized around an arborizing array of arterioles that branch and narrow until they terminate in either (1) the stroma of cords, forming the open circulation, or (2) the sinusoids, forming the closed circulation of the spleen (Chap. 6). The cordal elements include histiocytes, antigen-presenting cells, pericytes, fibroblasts, and other cells necessary to maintain the discontinuous basal lamina that separates cords from sinusoid lumen.¹³ Lymphatic tissue is inconspicuous and found in T-cell–rich zones in the periarteriolar lymphoid sheaths.

The arterial vascular tree, which is lined by conventional CD31+ and CD34+ endothelial cells, branches into arterioles that terminate abruptly in caps of cordal macrophages. Blood cells must pass clusters of macrophages to enter the sinusoids.¹³ The sinusoids, the origin of the venous circulation, are lined by specialized cells having combined phagocytic and endothelial activities and a distinctive CD31+, CD34−, CD68+, CD8+ phenotype. A principal function of the spleen is to serve as a filter, removing aged or defective red cells and foreign particles by macrophages. This function is facilitated by diverting part of the splenic blood supply into the red pulp, where the blood slowly percolates through the nonendothelialized mesh studded with macrophages. Abnormal or senescent red cells and pathogens undergo phagocytosis by the macrophages. The blood then reenters the circulation through narrow slits, measuring 1 to 3 μm, in the endothelium of the venous sinuses. The bulk of the blood is rapidly channeled through vessels that link the arterioles with the venous sinuses. This blood is not filtered or modified.¹⁴

Approximately one-third of platelets are normally sequestered in the spleen.¹⁵ In many animals, such as dogs and horses, the red pulp is a reservoir for red cells, and splenic contraction provides the red cell volume with a functionally important boost.¹⁶ In humans, however, the splenic capsule is poorly contractile, and the spleen does not store red cells to any significant degree.¹⁷ Although margination of neutrophils occurs in the spleen, it is unclear to what degree it occurs in that site.¹⁸ Granulocyte colony-stimulating factor (G-CSF) administered to cirrhotic patients caused a rise in the blood neutrophil count; thereafter, indium scans of the spleen were performed, which did not show significant uptake by white cells.¹⁹

The slow transit of blood through the red pulp permits macrophages to recognize and destroy antibody- or complement-coated red cells and microorganisms, and to ingest poorly deformable red cells or particles retained mechanically by the narrow exit slits in the venous sinuses. The white pulp plays a major role in adaptive immunity. The spleen is involved in the phagocytosis of encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.

PATHOPHYSIOLOGY

Filtration and elimination of defective cells occur notably in hereditary abnormalities of the red cell membranes, such as spherocytosis, elliptocytosis, or stomatocytosis, or with antibody-coated red cells, neutrophils, or platelets. In these circumstances, cytopenias of varying severity may ensue. The spleen not only removes antibody-coated cells, but also produces antibodies, especially antiplatelet antibodies.²⁰ Thus, the benefits of splenectomy in immune thrombocytopenic purpura is a result of both the decreased production of antiplatelet antibodies as well as decreased clearance by macrophages of antibody-coated platelets through the Fc recognition function of its large macrophage population.

Splenomegaly increases the proportion of blood channeled through the red pulp.^13,21 Spleen enlargement may result from expansion of the red pulp compartment with increased blood flow; extramedullary hematopoiesis, notable in primary myelofibrosis; hyperplasia or neoplasia involving the white pulp, such as in infectious mononucleosis or lymphoma; or histiophagocytic hyperplasia.

The increased size of the filtering bed is more pronounced when the splenomegaly is caused by congestion as in portal hypertension than when it is caused by cellular infiltration as in leukemias, extramedullary hematopoiesis, or amyloidosis. Even in space-occupying disorders such as Gaucher disease and primary myelofibrosis, splenomegaly may be associated with hypersplenic sequestration of normal cells.

Splenomegaly increases the vascular surface area and thereby the marginated neutrophil pool.^18,19 Platelets are especially likely to be sequestered in an enlarged spleen. However, sequestered white cells and platelets survive in the spleen and may be available when increased demand requires neutrophils or platelets, although their release may be slow.²²

Some patients with anemia and splenomegaly have a relative erythropoietin deficiency.²³ In one study of cirrhotic patients, 30 percent had a blunted erythropoietin response to anemia.²⁴ Dilution of red cells in an expanded plasma volume is another commonly cited cause of a decreased blood hemoglobin concentration,²⁵ although some studies do not demonstrate hemodilution.²⁶ Iron deficiency associated with chronic blood loss, folic acid and vitamin B₁₂ deficiency, and increased red cell destruction are frequently investigated, although rarely found in patients with liver disease.²⁷ Red cells are destroyed prematurely in the red pulp in the setting of splenomegaly, but only rarely does this explain the anemia.²⁸

Varying amounts of erythrophagocytosis are present, reflecting the normal culling of senescent red cells. Erythrophagocytosis increases as a result of hemolytic anemia and viral infections, and in alloimmunized transfusion recipients. Macrophages within the sinusoids contain red cell fragments. When the process is pronounced, the littoral cells become cuboidal and stand out on the basement membrane (“hobnails”). Sickle cell disease and red cell membrane disorders such as hereditary spherocytosis lead to sequestration of the poorly deformed red cells in the cords but little extrasinusoidal erythrophagocytosis is seen, in contrast to immune hemolytic anemia where macrophage erythrophagocytosis is prominent.¹³

The increased blood flow from an enlarged spleen expands the splenic and portal veins. A significant increase in portal venous pressure may occur when hepatic vessel compliance is decreased, as in cirrhosis or myelofibrosis. This process initiates a vicious cycle in which portal hypertension contributes to splenomegaly, organ enlargement leads to increased arterial blood flow, which, in turn, increases portal pressure.

Table 56–1 lists causes of splenomegaly, and Table 56–2 lists causes of massive splenic enlargement.

Table 56–1.Classification and Most Common Causes of Splenomegaly

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Table 56–1. Classification and Most Common Causes of Splenomegaly

1. Congestive

a. Right-sided congestive heart failure

b. Budd-Chiari syndrome (inferior vena cava and hepatic vein thrombosis)

c. Cirrhosis with portal hypertension

d. Portal or splenic vein thrombosis

2. Immunologic

a. Viral infection

i. Acute HIV infection/chronic Infection

ii. Acute mononucleosis

iii. Dengue fever

iv. Rubella (rare except newborns)

v. Cytomegalovirus (rare except newborns)

vi. Herpes simplex (rare except newborns)

b. Bacterial infection

i. Subacute bacterial endocarditis

ii. Brucellosis

iii. Tularemia

iv. Melioidosis

v. Listeriosis

vi. Plague

vii. Secondary syphilis

viii. Relapsing fever

ix. Psittacosis

x. Ehrlichiosis

xi. Rickettsial diseases (scrub typhus, Rocky Mountain spotted fever, Q fever)

xii. Tuberculosis

xiii. Splenic abscess (most common organisms are Enterobacteriaceae, Staphylococcus aureus, Streptococcus group D, and anaerobic organisms as part of mixed flora infections)

c. Fungal infection

i. Blastomycosis

ii. Histoplasmosis

iii. Systemic candidiasis; hepatosplenic candidiasis

d. Parasitic infection

i. Malaria

ii. Kala-Azar

iii. Leishmaniasis

iv. Schistosomiasis

v. Babesiosis

vi. Coccidioidomycosis

vii. Paracoccidioidomycosis

viii. Trypanosomiasis (cruzi, brucei)

ix. Toxoplasmosis (rare except newborns)

x. Echinococcosis

xi. Cysticercosis

xii. Visceral larva migrans (Toxocara infection)

e. Inflammatory/autoimmune

i. Systemic lupus erythematosus

ii. Felty syndrome

iii. Juvenile rheumatoid arthritis

iv. Autoimmune lymphoproliferative syndrome (ALP syndrome)

v. Hemophagocytic syndrome

vi. Common variable immunodeficiency

vii. Splenomegaly caused by granulocyte colony-stimulating factor administration

viii. Anti-D immunoglobulin administration (RhoGAM)

3. Secondary to hemolysis

a. Thalassemia major

b. Pyruvate kinase deficiency

c. Hereditary spherocytosis

d. Autoimmune hemolytic anemia (uncommon)

e. Sickle cell disease in early childhood (splenic sequestration)

4. Infiltrative

a. Nonmalignant

i. Splenic hematoma (splenic cysts are usually a late complication of a hematoma)

ii. Littoral cell angioma

iii. Disorders of sphingolipid metabolism

1. Gaucher disease

2. Niemann-Pick disease

iv. Cystinosis

v. Amyloidosis (light chain amyloid [AL] and amyloid A protein [AA])

vi. Multicentric Castleman disease

vii. Mastocytosis

viii. Hypereosinophilic syndrome

ix. Sarcoidosis

b. Extramedullary hematopoiesis

i. Primary myelofibrosis

ii. Osteopetrosis (childhood)

iii. Thalassemia major

c. Malignant

i. Hematologic

1. Chronic lymphocytic leukemia (especially prolymphocytic variant)

2. Chronic myeloid leukemia

3. Polycythemia vera

4. Hairy cell leukemia

5. Heavy chain disease

6. Hepatosplenic lymphoma

7. Acute leukemia (acute lymphoblastic leukemia/acute myeloid leukemia)

8. Hodgkin lymphoma

ii. Nonhematologic

1. Metastatic carcinoma (rare)

2. Neuroblastoma

3. Wilms tumor

4. Leiomyosarcoma

5. Fibrosarcoma

6. Malignant fibrous histiocytoma

7. Kaposi sarcoma

8. Hemangiosarcoma

9. Lymphangiosarcoma

10. Hemangioendothelial sarcoma

Table 56–2.Causes of Massive Splenomegaly

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Table 56–2. Causes of Massive Splenomegaly

Myeloproliferative disorders
1. Primary myelofibrosis
2. Chronic myeloid leukemia
Lymphomas
1. Hairy cell leukemia
2. Chronic lymphocytic leukemia (especially prolymphocytic variant)
Infectious
1. Malaria
2. Leishmaniasis (kala azar)
Extramedullary hematopoiesis
1. Thalassemia major
Infiltrative
1. Gaucher disease

CLINICAL FEATURES

Slight to moderate enlargement of the spleen usually does not produce local symptoms. Even massive splenomegaly can be well tolerated if it develops gradually. However, not infrequently, the patient complains of a sagging feeling or other types of abdominal discomfort, early satiety from gastric encroachment, and trouble sleeping on one side. Pleuritic pain in the left upper quadrant or referred to the left shoulder may accompany splenic infarcts, which may be recurrent.

In children with sickle cell anemia or patients with malaria, the spleen may become acutely enlarged and painful as a result of a sudden increase in red cell pooling and sequestration. These sequestration crises are characterized by sudden aggravation of the anemia. Splenic rupture is uncommon but can occur spontaneously with most causes of splenic enlargement or after blunt trauma. Rupture related to the splenic enlargement in infectious mononucleosis is a classic example.

The volume of an enlarged spleen is difficult to assess by palpation and percussion. Children and thin patients with low diaphragms may have a palpable spleen tip without splenomegaly.²⁹ Generally, a palpable spleen signifies splenomegaly and is measured by the number of centimeters the spleen extends below the left costal margin. Splenic size is most accurately measured with abdominal ultrasound (Fig. 56–1) or computed tomographic scans (Fig. 56–2). Magnetic resonance imaging is used primarily to identify cysts, abscesses, and infarcts.³⁰

Figure 56–1.

A three-way composite of abdominal computerized tomography. A. Normal spleen size. B. Enlarged spleen. C. Massively enlarged spleen at the level of mid-kidney. Normally the spleen would either not be visualized or only a small lower pole would be evident at the level of the mid-kidney. (White arrow in each of the three images marks edge of splenic silhouette.) (Used with permission of Deborah Rubens, MD, The University of Rochester Medical Center.)

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Figure 56–2.

A two-way composite of ultrasonography examination for spleen size. A. Image of echo indicating normal spleen size with cranial to caudal longitudinal dimension of 10.3 cm. B. Image of echo indicating enlarged spleen with cranial to caudal longitudinal dimension of 16.2 cm. (White arrow in each image marks edge of splenic silhouette.) The normal spleen is usually less than 13 cm in length but the examiner has to consider other dimensions in assessing spleen size (volume). (Used with permission of Deborah Rubens, MD, The University of Rochester Medical Center.)

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SPLENOPTOSIS

A wandering spleen (splenoptosis) is an uncommon phenomenon in which the spleen hangs by a long pedicle of mesentery. The condition may present in three ways: (1) an asymptomatic mass in the pelvis, (2) intermittent abdominal pain with or without gastrointestinal symptoms, or, less often, (3) an acute abdomen resulting from torsion. The diagnosis of splenoptosis may be made coincidentally on an imaging study.³¹ The condition may be accompanied by signs of hypersplenism, hyposplenism, and often, when developing slowly, is initially mistaken for a pelvic or lower abdominal tumor.

LABORATORY FEATURES

The characteristic features of hypersplenism are splenomegaly, blood cytopenias, and absence of other causes of cytopenias (e.g., anemia caused by bleeding). The blood cell morphology usually is normal, although a few spherocytes may result from metabolic conditioning of red cells during repeated slow transits through the expanded red pulp. Tests, such as epinephrine mobilization, were used in the past to try to distinguish sequestration from ineffective cellular production, but results are difficult to interpret as epinephrine also releases platelets and neutrophils from marginal pools.³²

Thrombocytopenia is a common finding in patients with hepatic cirrhosis, portal hypertension, and splenomegaly. In a retrospective study, 64 percent of patients with nonalcoholic cirrhosis had thrombocytopenia.³³ Other studies have found that approximately one-third of patients with cirrhosis develop severe thrombocytopenia or neutropenia.^34,35 Decompensated liver disease and history of alcohol consumption are independent risk factors for hypersplenism,³⁶ but why some patients develop marked blood cytopenias is not clear, although folate deficiency is a factor in some instances. The presence of thrombocytopenia or leukopenia in patients with chronic liver disease is associated with increased mortality.³⁷

Ultrasound-guided fine-needle biopsy of the spleen can be useful in circumstances in which the spleen holds the tissue required for diagnosis, such as splenic lymphoma. However, fine-needle aspiration is rarely a definitive diagnostic tool but can indicate monoclonality of splenic lymphocytes, which is helpful and forces further diagnostic evaluation. Aspiration cytology and core biopsy can be obtained with relative safety in experienced hands using image-guided fine needles.³⁸

The response to transfusion of blood products, especially platelets, may be significantly impaired in patients with massive splenomegaly.³⁹

THERAPY, COURSE, AND PROGNOSIS

Total Splenectomy

Splenectomy is indicated as an emergency procedure after abdominal trauma and partial rupture of the spleen. It also may be indicated when splenic size or infarcts causes sustained left upper abdominal pain or discomfort. Splenectomy has been used for the treatment of functionally significant blood cytopenias.³⁹ In such circumstances, case reports have described dramatic restoration of blood counts to normal levels within days to weeks after splenectomy; however, the only controlled trial evaluating relief of cytopenias showed no improvement.⁶ Orthotopic liver transplant corrects the cytopenias in the majority of patients with cirrhosis.⁴⁰

Hereditary spherocytosis, immune thrombocytopenic purpura, and immune hemolytic anemia are the most common indications for splenectomy. Splenectomy exerts its effect in autoimmune cytopenias by improving cell survival and also by decreasing autoantibody production. In thalassemia major, an improvement in the anemia is well described after splenectomy. In such cases, splenectomy may improve the response to transfusion. Some children with sickle cell anemia may benefit from splenectomy if repeated sequestration crises with abdominal pain occur before autosplenectomy renders the spleen atrophic.⁴¹

Splenectomy in patients with a massive spleen size (>1500 g), especially in primary myelofibrosis, is accompanied by higher morbidity and mortality than is removal of the spleen for immune blood cytopenia.⁴² Possible postoperative complications include extensive adhesions with collateral blood vessels, hepatic or portal vein thrombosis, injury to the tail of the pancreas, operative site infections, and subdiaphragmatic abscesses.

Laparoscopic splenectomy performed by experienced surgeons for suitable hematologic conditions can result in less abdominal trauma and pain, shorter hospital stays, and smaller abdominal scars.⁴³ An advantage of open splenectomy in hematologic conditions such as the treatment of immune thrombocytopenic purpura is the increased ease of searching assiduously for accessory spleens.

Partial Splenectomy

Partial splenectomy has been explored because it may minimize the risks of immediate postsplenectomy thrombocytosis and overwhelming sepsis that may result from a complete absence of splenic function.⁴⁴ However, the degree of thrombocytosis after splenectomy wanes to some degree with time postsplenectomy. Reduction of the splenic volume has been performed with ligation of some of the splenic arteries or the intraarterial infusion of Gelfoam particles causing embolization.^45,46,47,48 These procedures induce large splenic infarcts and reduce the functional splenic mass. Arterial embolization can be performed percutaneously or intravascularly, but the patients must be observed closely for a number of days to weeks to detect signs of intraabdominal rupture of the splenic infarcts. The long-term results of embolization have been encouraging.^46,47,48 Treatment with partial arterial embolization for recurrent thrombocytopenia in children temporarily improved the platelet count in approximately 70 percent of patients.⁴⁹

Splenic Radiation

Splenic radiation for treatment of an enlarged spleen is used sparingly. The procedure may be associated with severe cytopenias and especially thrombocytopenia (abscopal effect). It can be used in patients with an absolute contraindication to splenectomy who might benefit symptomatically from reduction of a massively enlarged spleen.⁵⁰

Liver Transplantation

Thrombopoietin synthesis and secretion are impaired in liver failure and this is corrected after liver transplantation.^51,52 However, thrombocytopenia may not be corrected after liver transplant if the splenomegaly persists.

Thrombopoietin Receptor Agonists

After thrombopoietin was cloned^53,54 several thrombopoietin mimetic drugs have been developed and tested. A phase II study reported that the oral thrombopoietin-receptor agonist (TPO-RA) eltrombopag increases platelet counts in patients with thrombocytopenia as a result of hepatitis C virus–related cirrhosis.⁵⁵ A phase III study done in cirrhotic patients who received eltrombopag for 2 weeks prior to elective procedures had to be terminated prematurely because of the increased incidence of portal vein thrombosis in the treatment group compared to the placebo group. Although 72 percent of the eltrombopag patients avoided platelet transfusions compared to 19 percent of the placebo group patients, there was no significant difference in the incidence of major bleeding.⁵⁶ A small study using the TPO-RA romiplostim administered subcutaneously in cirrhotic patients demonstrated the usefulness of the drug in reducing platelet transfusions in preparation for an elective surgical procedure.⁵⁷

Erythropoietin and Granulocyte Colony-Stimulating Factor

There are minimal data to support the use of erythropoietic or myeloid growth factors in patients with splenomegaly and blood cytopenias. Patients with cirrhosis who have inappropriately low serum erythropoietin levels may benefit from treatment with exogenous erythropoietin; however, it may increase spleen size. Two reports documented the use of erythropoietin before and after liver transplantation to amplify marrow erythropoiesis in patients who refused blood transfusions for religious reasons.^58,59 These reports demonstrated that liver transplantation in the setting of advanced cirrhosis can be successfully undertaken without the use of blood products.

A rise in the neutrophil count after G-CSF administration was described in patients with cirrhosis and leukopenia. The mean absolute neutrophil count increased from 1300 ± 200/μL to 4100 ± 200/μL following subcutaneous administration of G-CSF for 7 days.¹⁹ However, the clinical benefit of such treatment is not clear.

HYPOSPLENISM

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DEFINITION

Hyposplenism is the designation for decreased splenic function resulting from diseases that impair function or from the absence of splenic tissue because of agenesis, atrophy (e.g., autoinfarction of sickle cell disease), or splenectomy. Splenic hypofunction may be associated with a normal spleen size. In some cases, engorgement of ingested materials impairs the macrophage-dependent functions of the spleen. Impaired filtering function may cause a mild thrombocytosis. Functional or anatomical asplenia, especially after surgical removal in infants and children, increases the risk of an overwhelming bacterial infection. Table 56–3 lists conditions associated with hyposplenism.

Table 56–3.Conditions Associated with Hyposplenism

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Table 56–3. Conditions Associated with Hyposplenism

MISCELLANEOUS

Surgical splenectomy

Splenic irradiation

Sickle hemoglobinopathies

Congenital agenesis

Thrombosis of splenic artery or vein

Normal infants

GASTROINTESTINAL AND HEPATIC DISEASES

Celiac disease

Dermatitis herpetiformis

Inflammatory bowel disease

Cirrhosis

AUTOIMMUNE DISORDERS

Systemic lupus erythematosus

Rheumatoid arthritis

Vasculitis

Glomerulonephritis

Hashimoto thyroiditis

Sarcoidosis

HEMATOLOGIC AND NEOPLASTIC DISORDERS

Graft versus host disease

Essential thrombocytosis

Chronic lymphocytic leukemia

Non-Hodgkin lymphoma

Hodgkin lymphoma

Amyloidosis

Advanced breast cancer

Hemangiosarcoma

SEPSIS/INFECTIOUS DISEASES

Malaria

Disseminated meningococcemia

CLINICAL FEATURES

The normal neonate and the elderly adult may have findings suggestive of impaired splenic function.⁶⁰ These include the presence of Howell-Jolly bodies and erythrocyte pits (see “Laboratory Features” below). However, the clinical significance of functional hyposplenism is uncertain.^61,62,63

Sickle cell anemia and surgical splenectomy are the most common causes of hyposplenism. In sickle cell anemia, hyposplenism may be functional in young children with enlarged spleens and disordered circulation and may be the result of atrophy after repeated infarcts have destroyed splenic tissue in older children and adults. Although the presence of an enlarged spleen usually suggests hypersplenism, spleen size is not a reliable index of splenic function. Complete splenic replacement by cysts, neoplastic tissue, or amyloid is an example of hyposplenic splenomegaly.⁶⁴ Acute sequestration crises in children with sickle hemoglobinopathies, and occasionally in patients with malaria, may clog the red cell pulp with cellular debris and lead to hyposplenism.^65,66

Congenital asplenia may be found in infants with situs inversus and other developmental abnormalities.³⁸ Autoimmune disorders, such as glomerulonephritis,⁶⁷ systemic lupus erythematosus,^68,69 and rheumatoid arthritis,⁷⁰ are occasionally associated with laboratory evidence and clinical manifestations (overwhelming sepsis with encapsulated bacteria) of functional hyposplenism. Hyposplenism also occurs in chronic graft-versus-host disease,^71,72 sarcoidosis,⁷³ alcoholic liver cirrhosis,^74,75 hepatic amyloidosis,^76,77 celiac disease,^78,79 and inflammatory bowel disease.^80,81 The mechanisms for these associations are unknown.

Splenic replacement by neoplastic cells, as in lymphomas and leukemias, usually does not cause hyper- or hyposplenism. Splenic irradiation⁸² and vascular obstruction⁸³ may also lead to functional hyposplenism.

Overwhelming Sepsis

Absence of a functional spleen may lead to life-threatening infections by removal of an efficient filtering bed in which opsonized organisms are engulfed and destroyed by splenic macrophages. The responsible organism is typically an encapsulated bacteria, such as S. pneumoniae, N. meningitidis, or H. influenzae. Unrestrained in vivo proliferation of such microorganisms may cause fatal septicemia.^84,85,86 The risk is greatest among infants whose general immunologic system has not matured enough to counteract bacterial infections, although the risk is present regardless of the patient’s age. For this reason, splenectomy in children should be deferred until 5 years of age, if possible. The risk of sepsis varies depending on the reason for the splenectomy. In a child with an underlying immune disorder, such as Wiskott-Aldrich syndrome, the risk is very high. The infectious risk is higher in children with thalassemia than in those with hereditary spherocytosis and lowest in those with splenectomy for splenic trauma. The risk is reduced by the use of pneumococcal and H. influenzae vaccines prior to splenectomy and prophylactic penicillin therapy.⁸⁷

Because the spleen is a major component of the mononuclear phagocyte system and has substantial lymphatic tissue in the white pulp, hyposplenism or splenectomy can also reduce antibody synthesis that may be beneficial in the management of autoimmune disorders.

LABORATORY FEATURES

The reduction or absence of normal splenic function is accompanied by a slight to moderate increase in white cell and platelet counts. Howell-Jolly bodies, target cells, Pappenheimer (siderotic) bodies, and occasional acanthocytes often are present in the blood film, but the finding of pitted erythrocytes in wet preparations is the most specific of all the blood findings.⁸⁸ Target cells reflecting an increased red cell surface⁸⁹ are almost always present in the asplenic state, but only 1 in 100 to 1 in 1000 red cells is affected. A sensitive indication of hyposplenism is the appearance of pits or pocks on the cell surface.⁹⁰ These pits consist of submembranous vacuoles and can be seen only in wet preparations of red cells using direct interference-contrast microscopy. Intracellular vesiculation containing hemoglobin is a normal occurrence during aging of the red cell in the circulation. This process is intensified in the last half of the erythrocyte life span and leads to a decreased mean cell hemoglobin level as the vesicles are removed (pitted) by the spleen. In asplenic individuals the vesicles are more numerous and enlarge, forming vacuoles that are evident by interference-phase microscopy.⁸⁸ This finding is the most specific evidence of hyposplenism, followed by the presence of DNA inclusions in circulating red cells (Howell-Jolly bodies; Fig. 56–3).

Figure 56–3.

Blood film of splenectomized patient showing three red cells with Howell-Jolly bodies (nuclear remnants). Note also the cluster of acanthocytes and scattered spheroacanthocytes and the target cell. These changes are also indicative of postsplenectomy red cell changes. (Reproduced with permission from Lichtman’s Atlas of Hematology, www.accessmedicine.com.)

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Oxidative drugs may produce Heinz bodies even in normal individuals, but the spleen effectively removes these red cell inclusions, as well as Pappenheimer bodies. Heinz bodies may be observed in supravitally stained blood films after splenectomy. Nucleated red cells rarely are seen on blood films after splenectomy, except in patients with hemolytic disorders in whom the number of nucleated red cells may increase dramatically. The reticulocyte count remains within normal values, and the life span of red cells is unchanged as other organs take up the function of removing senescent erythrocytes.

Technetium-99m sulfur-colloid particles are used for spleen scanning, a reliable measure of the capacity of the spleen to clear particulate matter from the bloodstream.⁹¹

THERAPY, COURSE, AND PROGNOSIS

Vaccination against H. influenzae, N. meningitidis, and S. pneumoniae is recommended in previously unvaccinated individuals prior to splenectomy.⁹² Prophylactic immunization has significantly reduced, but not eliminated, the risk of overwhelming infection.^87,93,94,95 Oral penicillin or a macrolide antibiotic as prophylaxis for asplenic patients is recommended based on publicized guidelines despite problems with compliance and resistance.^96,97 Physicians should advise all asplenic patients that any febrile episode (>38°C) should be considered an emergency requiring immediate medical attention. A febrile asplenic patient must have blood and urine cultures drawn, followed by antibiotic treatment. Patients should be given written information about asplenia and carry a card or medical alert bracelet to alert health professionals of the risk of overwhelming infection.^96,97 Dental work, especially tooth extraction, should be preceded by broad-spectrum antibiotics, such as amoxicillin, if the patient is not taking prophylactic antibiotics. Patients should be educated about risks of travel, including risk of malaria infection or animal bites, which could be deadly unless promptly treated.^96,97

REFERENCES

Listen

Crosby WH: The spleen, in Blood, Pure and Eloquent, MM Wintrobe, edited by, p 96. McGraw-Hill, New York, 1980.

Chauffard AME: Des hepatites d’origine splenique. Semin Med 19:177, 1899.

Sutherland GA, Burghard FF: The treatment of splenic anaemia by splenectomy. Lancet 2:1819, 1910.

Kaznelson P: Verschwinden der hamorrhagischen Diathesis bei einen falle von “Essentieller Thrombopenia”. Wien Klin Wochenschr 29:1451, 1916.

Crosby WH: Hypersplenism. Annu Rev Med 13:127, 1962. [PubMed: 13882364]

Mutchnick MG, Lerner E, Conn HO: Effect of portacaval anastomosis on hypersplenism. Dig Dis Sci 25:929, 1980. [PubMed: 7004809]

Jabbour N, Zajko A, Orons P et al.: Does transjugular intrahepatic portosystemic shunt (TIPS) resolve thrombocytopenia associated with cirrhosis? Dig Dis Sci 43:2459, 1998. [PubMed: 9824134]

Roberts CW, Shutter JR, Korsmeyer SJ: Hox11 controls the genesis of the spleen. Nature 368:747, 1994. [PubMed: 7908720]

Dear TN, Colledge WH, Carlton MB et al.: The Hox11 gene is essential for cell survival during spleen development. Development 121:2909, 1995. [PubMed: 7555717]

10.

Roberts CW, Sonder AM, Lumsden A et al.: Developmental expression of HOV11 and specification of splenic cell fate. Am J Pathol 146:1089, 1995. [PubMed: 7747804]

11.

Steininger B, Barth P, Herbst B et al.: The species-specific structure of microanatomical compartments in the human spleen. Immunology 92:307, 1997. [PubMed: 9415041]

12.

Bourdessoule D, Gaulard P, Mason DY: Preferential localization of human lymphocytes bearing −/− T cell receptors to the red pulp of the spleen. J Clin Pathol 43:461, 1990. [PubMed: 2143201]

13.

Kraus MD: Splenic histology and histopathology: An update. Semin Diagn Pathol 20:84, 2003. [PubMed: 12945932]

14.

Rosse WF: The spleen as a filter [editorial]. N Engl J Med 317:704, 1987. [PubMed: 3627175]

15.

Bowdler AJ: Splenomegaly and hypersplenism. Clin Haematol 12:467, 1983. [PubMed: 6352112]

16.

Areas Elenas N, Ewald R, Crosby WH: The reservoir function of the spleen and its relation to postsplenectomy anemia of the dog. Blood 24:299, 1964. [PubMed: 14214138]

17.

Wadenvik H, Kutti J: The spleen and pooling of blood cells. Eur J Haematol 41:1, 1988. [PubMed: 3042452]

18.

Aster RH: Pooling of platelets in the spleen: Role in the pathogenesis of “hypersplenic thrombocytopenia.” J Clin Invest 45:645, 1966. [PubMed: 5327481]

19.

Gurakar A, Fagiuoli S, Gavaler JS et al.: The use of granulocyte-macrophage colony-stimulating factor to enhance hematologic parameters of patients with cirrhosis and hypersplenism. J Hepatol 21:582, 1994. [PubMed: 7814805]

20.

Karpatkin S: The spleen and thrombocytopenia. Clin Haematol 12:591, 1983. [PubMed: 6352117]

21.

Zwiebel WJ, Mountford RA, Halliwell MJ, Wells PN: Splanchnic blood flow in patients with cirrhosis and portal hypertension: Investigation with duplex Doppler US. Radiology 194:807, 1995. [PubMed: 7862983]

22.

Brubaker LH, Johnson CA: Correlation of splenomegaly and abnormal neutrophil pooling (margination). J Lab Clin Med 92:508, 1978. [PubMed: 712190]

23.

Siciliano M, Tomasello D, Milani A et al.: Reduced serum levels of immunoreactive erythropoietin in patients with cirrhosis and chronic anemia. Hepatology 22:1132, 1995. [PubMed: 7557862]

24.

Vasilopoulos S, Hally R, Caro J et al.: Erythropoietin response to post-liver transplantation anemia. Liver Transpl 6:349, 2000. [PubMed: 10827238]

25.

Hess CE, Ayers CR, Sandusky WR et al.: Mechanism of dilutional anemia in massive splenomegaly. Blood 47:629, 1976. [PubMed: 1260126]

26.

Zhang B, Lewis SM: Splenic hematocrit and the splenic plasma pool. Br J Haematol 66:97, 1987. [PubMed: 3593658]

27.

Jandl JH: The anemia of liver disease: Observations on its mechanism. J Clin Invest 34:390, 1955. [PubMed: 14354009]

28.

Christensen BE: Quantitative determination of splenic red cell blood destruction in patients with splenomegaly. Scand J Haematol 14:295, 1975. [PubMed: 1057239]

29.

McIntyre OR, Ebaugh FA: Palpable spleens in college freshmen. Ann Intern Med 66:301, 1967. [PubMed: 6016543]

30.

Sty JR, Wells RG: Imaging the spleen, in Disorders of the Spleen: Pathophysiology and Management, C Pochedly, RH Sills, AD Schwartz, edited by, p 355. Marcel Dekker, New York, 1989.

31.

Buehner M, Baker MS: The wandering spleen. Surg Gynecol Obstet 175:373, 1992. [PubMed: 1411897]

32.

Joyce RA, Boggs DR, Hasiba U, Srodes CH: Marginal neutrophil in the pool size in normal subjects as measured by epinephrine infusion. J Lab Clin Med 88:614, 1976. [PubMed: 787457]

33.

Alvarez OA, Lopera GA, Patel V et al.: Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients. Am J Gastroenterol 91:134, 1996. [PubMed: 8561113]

34.

Peck-Radosavljevic M: Hypersplenism. Eur J Gastroenterol Hepatol 13:317, 2001. [PubMed: 11338057]

35.

Bashour FN, Teran JC, Mullen KD: Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol 95:2936, 2000. [PubMed: 11051371]

36.

Liangpunsakul S, Ulmer BJ, Chalasani N: Predictors and implications of severe hypersplenism in patients with cirrhosis. Am J Med Sci 326:111, 2003. [PubMed: 14501224]

37.

Qamar A, Grace N, Groszmann R et al.: Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis. Clin Gastroenterol Hepatol 7:689, 2009. [PubMed: 19281860]

38.

Civardi G, Vallisa D, Berte R et al.: Ultrasound guided fine needle biopsy of the spleen: High clinical efficacy and low risk in a multicenter Italian study. Am J Hematol 67:93, 2001. [PubMed: 11343380]

39.

Pochedly C, Sills RH, Schwartz A: Disorders of the Spleen: Pathophysiology and Management. Marcel Dekker, New York, 1989.

40.

Yanaga K, Tzakis A, Shimade M, Campbell W et al.: Reversal of hypersplenism following orthotopic liver transplantation. Ann Surg 210:180, 1989. [PubMed: 2667473]

41.

Al-Salem AH, Qaisaruddin S, Nasserallah Z et al.: Splenectomy in patients with sickle-cell disease. Am J Surg 172:254, 1996. [PubMed: 8862078]

42.

Mohren M, Markman I, Dworschak U et al.: Thromboembolic complications after splenectomy for hematologic diseases. Am J Hematol 76:143, 2004. [PubMed: 15164380]

43.

Caprotti R, Porta G, Franciosi C et al.: Laparoscopic splenectomy for hematological disorders. Int Surg 83:303, 1998. [PubMed: 10096747]

44.

Bar-Moor JA: Partial splenectomy in Gaucher’s disease. J Pediatr Surg 28:686, 1993. [PubMed: 8340859]

45.

Banani SA: Partial dearterialization of the spleen in thalassemia major. J Pediatr Surg 33:449, 1998. [PubMed: 9537555]

46.

Stanley P, Shen TC: Partial embolization of the spleen in patients with thalassemia. J Vasc Interv Radiol 6:137, 1995. [PubMed: 7703580]

47.

Palsson B, Hallen M, Forsberg AM, Alwmark A: Partial splenic embolization: Long-term outcome. Langenbecks Arch Surg 387:421, 2003. [PubMed: 12607123]

48.

Petersons A, Volrats O, Bernsteins A: The first experience with nonoperative treatment of hypersplenism in children with portal hypertension. Eur J Pediatr Surg 12:299, 2002. [PubMed: 12469254]

49.

Watanabe Y, Todani T, Noda T: Changes in splenic volume after partial splenic embolization in children. J Pediatr Surg 31:241, 1996. [PubMed: 8938350]

50.

Paulino AC, Reddy AC: Splenic irradiation in the palliation of patients with lymphoproliferative and myeloproliferative disorders. Am J Hosp Palliat Care 13:32, 1996. [PubMed: 8945101]

51.

Peck-Radosavljevic M, Wichlas M, Zacherl J et al.: Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production. Blood 95:795, 2000. [PubMed: 10648388]

52.

Rios R, Sangro B, Herrero I et al.: The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol 100:1311, 2005. [PubMed: 15929762]

53.

Lok S, Kaushansky K, Holly RD et al.: Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 369:565, 1994. [PubMed: 8202158]

54.

de Sauvage FJ, Hass PE, Spencer SD et al.: Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 369:533, 1994. [PubMed: 8202154]

55.

McHutchinson JG, Dusheiko G, Shiffman ML et al.: Eltrombopag in patients with cirrhosis associated with hepatitis C. N Engl J Med 357:2227, 2007. [PubMed: 18046027]

56.

Afdhal NH, Giannini EG, Tayyab G et al.: Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 23;367, 2012.

57.

Moussa MM, Mowafy N: Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. J Gastroenterol Hepatol 28(2):335, 2013. [PubMed: 22849409]

58.

Ramos H, Todo S, Kang Y et al.: Liver transplantation without the use of blood products. Arch Surg[Archives of Surgery Full Text] 129:528, 1994. [PubMed: 8185476]

59.

Snook NJ, O’Beirne HA, Enright S et al.: Use of recombinant human erythropoietin to facilitate liver transplantation in a Jehovah’s Witness. Br J Anaesth 76:740,1996. [PubMed: 8688281]

60.

Freedman RM, Johnston D, Mahoney MJ et al.: Development of splenic reticuloendothelial function in neonates. J Pediatr 96:466, 1980. [PubMed: 6987357]

61.

Padmanabhan J, Risemberg HM, Rome RD: Howell-Jolly bodies in the peripheral blood of full-term and premature neonates. Johns Hopkins Med J 132:146, 1973. [PubMed: 4691170]

62.

Markus HS, Toghill PJ: Impaired splenic function in elderly people. Age Ageing 20:287, 1991. [PubMed: 1927737]

63.

Ravaglia G, Forti P, Biagi F et al.: Splenic function in old age. Gerontology 44:91, 1998. [PubMed: 9523220]

64.

Steinberg MH, Gatling RR, Tavassoli M: Evidence of hyposplenism in the presence of splenomegaly. Scand J Haematol 31:437, 1983. [PubMed: 6685914]

65.

Looareesuwan S, Ho M, Wallanagoon Y et al.: Dynamic alteration in splenic function during acute falciparum malaria. N Engl J Med 317: 675, 1987. [PubMed: 3306376]

66.

Emond AM, Callis R, Darvill D et al.: Acute splenic sequestration in homozygous sickle cell disease: Natural history and management. J Pediatr 107:201, 1985. [PubMed: 4020541]

67.

Lawrence SE, Pussell BA, Charlesworth JA: Splenic function in primary glomerulonephritis. Adv Exp Med Biol 641:1, 1982.

68.

Webster J, Williams BD, Smith AP et al.: Systemic lupus erythematosus presenting as pneumococcal septicemia and septic arthritis. Ann Rheum Dis 49:181, 1990. [PubMed: 2322028]

69.

Liote F, Angle J, Gilmore N, Osterland CK: Asplenism and systemic lupus erythematosus. Clin Rheumatol 14:220, 1995. [PubMed: 7789066]

70.

Jarolim DR: Asplenia and rheumatoid arthritis [letter]. Ann Intern Med 97:61, 1982. [PubMed: 7046555]

71.

Kalhs P, Panzer S, Kletter K et al.: Functional asplenia after bone marrow transplantation. Ann Intern Med 109:461, 1988. [PubMed: 3046449]

72.

Cuthbert RJ, Iqbal A, Gates A et al.: Functional hyposplenism following allogeneic bone marrow transplantation. J Clin Pathol 48:257, 1995. [PubMed: 7730489]

73.

Stone RW, McDaniel WR, Armstrong EM et al.: Acquired functional asplenia in sarcoidosis. J Natl Med Assoc 77:930, 1985. [PubMed: 3908697]

74.

Muller AF, Toghill PJ: Splenic function in alcoholic liver disease. Gut 33:1386, 1992. [PubMed: 1446865]

75.

Muller AF, Toghill PJ: Functional hyposplenism in alcoholic liver disease: A toxic effect of alcohol? Gut 35:679, 1994. [PubMed: 8200565]

76.

Gertz MA, Kyle RA: Hepatic amyloidosis (primary [AL], immunoglobulin light chain): The natural history in 80 patients. Am J Med 85:73, 1988. [PubMed: 3389383]

77.

Powsner RA, Simms RW, Chudnovsky A et al.: Scintigraphic functional hyposplenism in amyloidosis. J Nucl Med 39:221, 1998. [PubMed: 9476921]

78.

Robinson PJ, Bullen AW, Hall R et al.: Splenic size and functions in adult coeliac disease. Br J Radiol 53:532, 1980. [PubMed: 7426864]

79.

O’Grady JG, Stevens FM, Harding B et al.: Hyposplenism and gluten sensitive enteropathy. Gastroenterology 87:1316, 1984.

80.

Palmer KR, Sherriff SB, Holdsworth CD et al.: Further experience of hyposplenism in inflammatory bowel disease. Q J Med 50:461, 1981.

81.

Muller AF, Toghill PJ: Hyposplenism in gastrointestinal disease. Gut 36:165, 1995. [PubMed: 7883209]

82.

Dailey MO, Coleman CN, Kaplan HS: Radiation-induced splenic atrophy in patients with Hodgkin disease and non-Hodgkin lymphoma. N Engl J Med 302:215, 1990.

83.

Spencer RP, Sziklas JJ, Turner JW: Functional obstruction of splenic blood vessel in adults: A radiocolloid study. Int J Nucl Med Biol 9:208, 1982. [PubMed: 7129789]

84.

Torres J, Bisno AL: Hyposplenism and pneumococcemia. Am J Med 55:851, 1973. [PubMed: 4148153]

85.

Cavenagh JD, Joseph AE, Dilly S, Bevan DH: Splenic sepsis in sickle cell disease. Br J Haematol 86:187, 1994. [PubMed: 8011527]

86.

Gopal V, Bisno AL: Fulminant pneumococcal infections in “normal” asplenic hosts. Arch Intern Med[Archives of Internal Medicine Full Text] 137:1526, 1977. [PubMed: 921438]

87.

Konradsen HB, Henrichsen J: Pneumococcal infections in splenectomized children are preventable. Acta Paediatr Scand 80:423, 1991. [PubMed: 2058391]

88.

Corazza GR, Ginaldi L, Zoli G et al.: Howell-Jolly body counting as a measure of splenic function: A reassessment. Clin Lab Haematol 12:269, 1990. [PubMed: 2125541]

89.

Holroyde CP, Oski FA, Gardner FH: The “pocked” erythrocytes. N Engl J Med 281:516, 1969. [PubMed: 4895379]

90.

Reinhart WH, Chien S: Red cell vacuoles: Their size and distribution under normal conditions and after splenectomy. Am J Hematol 27:265, 1988. [PubMed: 3354561]

91.

Rutland MD: Correlation of splenic function with the splenic uptake rate of Tc-colloids. Nucl Med Commun 13:843, 1992. [PubMed: 1470428]

92.

Kobel DE, Friedl A, Cerny T et al.: Pneumococcal vaccine in patients with absent or dysfunctional spleen. Mayo Clin Proc 75:749, 2000. [PubMed: 10907393]

93.

Ward KM, Celebi JT, Gmyrek R, Grossman ME: Acute infectious purpura fulminans associated with asplenism or hyposplenism. J Am Acad Dermatol 47:493, 2002. [PubMed: 12271289]

94.

Sumaraju V, Smith LG, Smith SM: Infectious complications in asplenic hosts. Infect Dis Clin North Am 15:551, 2001. [PubMed: 11447709]

95.

Castagnola E, Fioredda F: Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: A brief review of current recommendations for practical purposes. Eur J Haematol 71:319, 2003. [PubMed: 14667194]

96.

Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. BMJ 312:430, 1996. [PubMed: 8601117]

97.

Davies JM, Barnes R, Milligan D: Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med 2:440, 2002. [PubMed: 12448592]

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Chapter 56: Hypersplenism and Hyposplenism

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INTRODUCTION

HYPERSPLENISM

HISTORY

DEFINITION

ONTOGENY

STRUCTURE AND FUNCTIONAL ORGANIZATION

PATHOPHYSIOLOGY

CLINICAL FEATURES

Figure 56–1.

Figure 56–2.

SPLENOPTOSIS

LABORATORY FEATURES

THERAPY, COURSE, AND PROGNOSIS

Total Splenectomy

Partial Splenectomy

Splenic Radiation

Liver Transplantation

Thrombopoietin Receptor Agonists

Erythropoietin and Granulocyte Colony-Stimulating Factor

HYPOSPLENISM

DEFINITION

CLINICAL FEATURES

Overwhelming Sepsis

LABORATORY FEATURES

Figure 56–3.

THERAPY, COURSE, AND PROGNOSIS

REFERENCES

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