HYPERSPLENISM

Shadi Hamdeh, MD • Adil Abdalla, MD

 BASICS

DESCRIPTION

•  Hypersplenism is defined as overactivity of the spleen and presents as the following:

–  Splenomegaly (commonly but not always)

–  Cytopenias with respective bone marrow hyperplasia of precursors

–  Resolution of cytopenias with splenectomy

•  Splenomegaly is not synonymous with hypersplenism. Overactivity of the spleen can occur without enlargement, as is seen in immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia. Similarly, splenomegaly is not always associated with hypersplenism.

EPIDEMIOLOGY

May be as common as 30–70% in patients with cirrhosis and portal hypertension (HTN)

ETIOLOGY AND PATHOPHYSIOLOGY

Enlargement of the spleen results in sequestration of formed blood elements, leading to peripheral cytopenias and concomitant bone marrow precursor hyperplasia.

Many of the common etiologies are listed below. Almost any process involving the spleen or the hematologic system can result in hypersplenism:

•  Infectious

–  Tuberculosis

–  Brucellosis

–  Malaria

–  Leishmaniasis

–  Ehrlichiosis

–  Schistosomiasis

–  Histoplasmosis

–  Candidiasis

–  Viral

–  Syphilis

–  Infective endocarditis

•  Hematologic

–  Myeloproliferative disorders

–  Polycythemia vera

–  Primary hypersplenism

–  ITP

–  Hemolytic anemias

•  Neoplastic

–  Hematologic malignancies

–  Melanoma

–  Various carcinomas

–  Metastatic cancers

•  Storage diseases

–  Gaucher disease

–  Niemann-Pick disease

–  Amyloidosis

–  Glycogen storage disease

•  Inflammatory

–  Sarcoidosis

–  Systemic lupus erythematosus

–  Felty syndrome

•  Congestive

–  Cirrhosis

–  Heart failure

–  Portal or splenic vein thrombosis

–  Congenital malformations of the portal vein

 DIAGNOSIS

HISTORY

•  Patients may complain of abdominal fullness or protrusion of the spleen through the abdominal wall; may complain of early satiety if the spleen is compressing stomach

•  Patients may complain of tenderness in the left upper quadrant, especially with viral infections. In lymphoproliferative disorders, spleen may be enlarged but asymptomatic unless there is splenic infarction. Given location of the spleen next to the diaphragm, a sense of fullness may be referred through the phrenic nerve to the C3–C5 dermatomes in the left shoulder.

•  Symptoms related to the underlying cause of hypersplenism may be present.

PHYSICAL EXAM

Splenomegaly

•  The normal spleen is not palpable. A palpable spleen always indicates underlying abnormality such as splenomegaly and, in turn, hypersplenism in the appropriate clinical context or may indicate a wandering spleen. Also, spleen can be palpated in chronic obstructive pulmonary disease and acute asthma exacerbation, without coexisting splenomegaly.

•  Begin by percussing Traube semilunar space, demarcated laterally by left anterior axillary line, inferiorly by the left costal margin, and superiorly by the left 6th rib. This space is usually hollow. Splenic enlargement may cause dullness to percussion in this area. Other processes that may cause dullness include pleural or pericardial effusions. Additionally, if the patient recently ate a large meal, this area may be dull to percussion.

•  With patient supine, rest hand gently on the abdomen to prevent sudden tensing of the abdominal musculature, which may obscure palpation. Better abdominal relaxation can be obtained by flexing the knees toward the abdomen. As the spleen enlarges, it moves caudally and medially. Start by palpating in the right lower quadrant and moving toward the umbilicus, toward the left upper quadrant. If there is doubt about whether the spleen has moved beyond the costal margin, ask patient to take a large breath, which will push the diaphragm, and, in turn, the spleen toward the examiner’s hands.

•  Jaundice: if hemolytic anemia is present or in advanced cirrhosis

•  Petechiae, purpura, or ecchymosis: if thrombocytopenia is present

•  Lymphadenopathy: in hematologic or solid organ malignancies. It also can be seen in infectious etiologies.

DIAGNOSTIC TESTS & INTERPRETATION

On CBC, any and all cell lines may be decreased, resulting in the following:

•  Anemia

•  Leukopenia

•  Thrombocytopenia

Initial Tests (lab, imaging)

•  CBC

•  Reticulocyte count if anemia

•  If there is hemolysis, there should be an elevated reticulocyte count, elevated LDH, decreased haptoglobin, along with evidence of hyperbilirubinemia (unconjugated).

•  US

•  CT

•  Tc-99m sulfur colloid scintigraphy

•  PET

•  MRI

Follow-Up Tests & Special Considerations

Based on other historical and exam findings, testing for specific infectious etiologies may be warranted:

•  Blood parasite smear for malaria and other parasitic infections

•  EBV serologies

•  HIV ELISA with Western blot

•  JAK2 mutation in polycythemia vera

•  PPD for tuberculosis

•  Hgb electrophoresis in hereditary hemoglobinopathies

Diagnostic Procedures/Other

•  Bone marrow biopsy

•  Liver biopsy for cirrhosis and storage diseases

Test Interpretation

Hyperplasia of bone marrow precursors, especially those correlating with the patient’s individual cytopenias

 TREATMENT

MEDICATION

•  No specific medication can be recommended for patients with hypersplenism. The most important intervention is to treat the underlying disorder.

•  If ITP is the cause, the patient may benefit from the following:

–  Prednisone or methylprednisolone

–  IVIG

–  Rituximab

•  If an infectious cause is discovered, treatment with appropriate antibiotic therapy may help to improve the cytopenias.

SURGERY/OTHER PROCEDURES

•  Many patients with severe uncontrolled cytopenias undergo splenectomy.

•  Laparoscopic splenectomy is preferred over open splenectomy (1)[A].

ALERT

•  Splenectomized patients should receive immunization to pneumococcus, meningococcus, Haemophilus influenzae, and influenza at least 14 days prior to splenectomy (2)[A].

•  If this cannot be done (i.e., in cases of emergent splenectomy), wait at least 14 days postsplenectomy to immunize.

–  Pneumococcal vaccine

  Pneumococcal polyvalent-23 vaccine (PPSV23) for use in adults and fully immunized children ≥2 years of age

  Pneumococcal polyvalent-13 vaccine (PCV13) for infants and young children ≥2 months of age as part of routine immunization schedule (3)[A]

  PCV13 for children >2 years of age, adolescents and adults in addition to PPSV23; refer to CDC for timing of administration

  Current guidelines recommend single revaccination of PPSV23 5 years after the initial dose and again at age of ≥65 years, at least 5 years after the previous dose.

–  H. influenzae vaccine

  All unvaccinated individuals ≥ 5 years of age should be given 1 dose of H. influenzae type B (Hib) conjugate vaccine.

  Children <5 years old should also be vaccinated. Refer to CDC for timing.

  Vaccinated individuals can also be given additional dose of vaccine (4)[A].

–  Meningococcal vaccine (5)[A]

  Meningococcal conjugate vaccine (MCV4) for use in patients between 2 and 55 years

  Meningococcal polysaccharide vaccine (MPSV4) for use in patients >55 years of age

  Revaccination is recommended every 5 years.

–  Influenza vaccine should be administered yearly based on prevalent circulating strains. Although patients are not at higher risk from influenza itself, infection with influenza may place patients at higher risk for secondary bacterial infections.

•  Radiofrequency ablation (RFA) is becoming more available and can be successful at preventing recurrence of hypersplenism. It is not currently known whether there are differences between RFA and splenectomy in terms of postprocedure infectious risks. Other alternatives to splenectomy include total and partial splenic embolization and shunting, although these techniques are evolving and additional studies are needed to evaluate efficacy and morbidity as compared to splenectomy.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

•  Hypersplenism alone generally does not warrant admission. However, all patients should be monitored closely for complications of the resulting cytopenias, including bleeding and infection, as well as complications of splenomegaly, including increased risk of splenic rupture. In some patients, the large spleen compresses the stomach and prevents adequate oral intake.

•  Splenectomized patients are at increased risk of infection and postsplenectomy sepsis, especially with Streptococcus pneumoniae. Fevers, chills, or pain concerning for underlying infection warrant immediate attention as clinical decompensation can occur within hours. Empiric broad-spectrum antibiotics should not be delayed while evaluation is ongoing. Common empiric regimens include the following:

–  Ceftriaxone: 2g IV q24h and vancomycin 1 g IV q12h

–  Levofloxacin: 750 mg IV q24h and vancomycin 1 g IV q12h in β-lactam–allergic patients

 ONGOING CARE

•  Adult patients who are splenectomized should be advised to monitor closely for fever or rigors at home, which may be an early sign of bacteremia. They should be instructed to begin antibiotics immediately prior to proceeding to a medical facility for evaluation. Early antibiotics have been shown to reduce the mortality from overwhelming postsplenectomy sepsis.

•  Controlled trials have not been performed, but some regimens include the following:

–  Amoxicillin-clavulanate: 875 mg PO twice daily

–  Cefuroxime axetil: 500 mg PO twice daily

•  Patients allergic to β-lactam antibiotics can be given an extended-spectrum fluoroquinolone such as levofloxacin 750 mg PO or moxifloxacin 400 mg PO daily.

•  In children with splenectomy, daily antibiotic prophylaxis for overwhelming postsplenectomy sepsis with penicillin VK or amoxicillin is recommended until age 5 or at least 3 years after splenectomy:

–  Age 2 months to 5 years: 125 mg PO BID

–  >5 years old: 250 mg PO BID

PATIENT EDUCATION

Patients who are splenectomized should be counseled extensively about the risk of overwhelming postsplenectomy sepsis and the need to obtain prompt medical evaluation in the event of fevers, chills, or any other concerning symptoms.

REFERENCES

1.  Bai YN, Jiang H, Prasoon P. A meta-analysis of perioperative outcomes of laparoscopic splenectomy for hematological disorders. World J Surg. 2012;36(10):2349–2358.

2.  Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2012. Ann Intern Med. 2012;156(3):211–217.

3.  American Academy of Pediatrics. Children with asplenia or functional asplenia. In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:72.

4.  American Academy of Pediatrics Committee on Infectious Diseases. Haemophilus influenzae type b conjugate vaccines: recommendations for immunization with recently and previously licensed vaccines. Pediatrics. 1993;92(3):480–488.

5.  Centers for Disease Control and Prevention. Updated recommendations for use of meningococcal conjugate vaccines—Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2011;60(3):72–76.

ADDITIONAL READING

•  Abdella HM, Abd-El-Moez AT, Abu El-Maaty ME, et al. Role of partial splenic arterial embolization for hypersplenism in patients with liver cirrhosis and thrombocytopenia. Indian J Gastroenterol. 2010;29(2):59–61.

•  Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378(9785):86–97.

•  Feng K, Ma K, Liu Q, et al. Randomized clinical trial of splenic radiofrequency ablation versus splenectomy for severe hypersplenism. Br J Surg. 2011;98(3):354–361.

•  Iriyama N, Horikoshi A, Hatta Y, et al. Localized, splenic, diffuse large B-cell lymphoma presenting with hypersplenism: risk and benefit of splenectomy. Intern Med. 2010;49(11):1027–1030.

•  Jandl JH, Aster RH, Forkner CE, et al. Splenic pooling and the pathophysiology of hypersplenism. Trans Am Clin Climatol Assoc. 1967;78:9–27.

•  Kapoor P, Singh E, Radhakrishnan P, et al. Splenectomy in plasma cell dyscrasias: a review of the clinical practice. Am J Hematol. 2006;81(12):946–954.

•  Mourtzoukou EG, Pappas G, Peppas G, et al. Vaccination of asplenic or hyposplenic adults. Br J Surg. 2008;95(3):273–280.

•  Shatz DV, Schinsky MF, Pais LB, et al. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy. J Trauma. 1998;44(5):760–765.

 SEE ALSO

Anemia, Autoimmune Hemolytic; Malaria; Polycythemia Vera; Tuberculosis

 CODES

ICD10

D73.1 Hypersplenism

CLINICAL PEARLS

•  Splenectomy is not necessary to make the diagnosis.

•  Avoid splenectomy in patients unless absolutely necessary. Splenectomized patients are at lifelong risk for overwhelming postsplenectomy infection and sepsis.

•  If splenectomy is to be performed, give immunization for pneumococcus, meningococcus, Haemophilus, and influenza at least 14 days prior to surgery. Otherwise, wait until the 14th postop day to immunize.