Splenomegaly Treatment & Management

Successful medical treatment of the primary disorder in cases of splenomegaly can lead to regression of the hypersplenism without the need for surgery.

Splenectomy is occasionally indicated to help control or stage the underlying disease in cases of splenomegaly. The most common indications for  therapeutic splenectomy include hereditary spherocytosis, immune thrombocytopenia (ITP), or autoimmune hemolysis where the splenomegaly is refractory to front line therapy and causing significant discomfort due to massive splenomegaly or complicated hypersplenism.

In addition, splenectomy enables pathologic diagnosis in lymphoproliferative disorders such as splenic marginal zone lymphoma or hairy cell leukemia. A review by Naples et al of splenectomy for idiopathic splenomegaly in 68 patients found that final surgical pathology of the removed spleen provided a definitive diagnosis for 44 patients (64.7%). Of those, 34 patients (50%) had an underlying malignancy, of which more than half were splenic marginal zone lymphoma. ^[20]  Of note, splenic marginal zone lymphoma secondary to hepatitis C can often resolve with treatment of the viral hepatitis, and cases not associated with hepatitis C can be treated with rituximab monotherapy thereby sparing the complications of splenectomy. 

Splenectomy is also indicated for the treatment of chronic, severe hypersplenism refractory to upfront medical therapy. ^[24] This can occur in conditions such as the following:

• Hairy cell leukemia
• Felty syndrome
• Primary myelofibrosis (agnogenic myeloid metaplasia)
• Thalassemia major
• Gaucher disease
• Hemodialysis splenomegaly
• Splenic vein thrombosis ^[10]

Treatment of splenic sequestration involves conservative management with blood transfusions/exchange transfusions to reduce the number of sickled red blood cells, or splenectomy. Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in sickle cell disease. ^[25]

In rare cases, splenectomy may be used to treat thrombotic thrombocytopenic purpura (TTP). However, therapeutic plasma exchange transfusion (plasmapheresis) has largely supplanted the need for splenectomy in these patients

Low-dose radiotherapy has been used as palliative care for splenomegaly in patients with hematologic disorders such as primary myelofibrosis. ^[26] Bruns et al reported that low-dose splenic irradiation produced hematologic response and long-term relief of splenic pain in four of five patients with symptomatic congestive splenomegaly. ^[27]

In a review by Zaorsky et al that included 766 courses of splenic irradiation for 486 patients from 1960 to 2016, the most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders. Splenic irradiation produced a partial or complete response in 85-90% of patients; 30% were retreated within 6-12months. ^[28]

Although the most common splenic irradiation regimen was 10Gy in 1Gy fractions over 2 weeks, these authors concluded that lower doses (eg, 5Gy in 5 fractions) might be as effective as higher doses, as they found no correlation between the biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement. ^[28]

Inpatient care

Inpatient care for patients with splenomegaly depends on the modality used to treat the underlying cause of the condition and on the complications of that care. These therapies are not unique to splenomegaly treatment and, therefore, are not discussed here.

Outpatient care

Outpatient care of patients with splenomegaly consists of three main focus areas: (1) primary etiologic disease; (2) blood count monitoring, especially when associated with a myeloproliferative disease as the cause; and (3) monitoring for overwhelming postsplenectomy infection (OPSI).

Thrombocytosis may require treatment when the platelet count exceeds 1 million/μL. Multiple modalities have been used to reduce the platelet count or inhibit their thrombotic effects, including hydroxyurea, aspirin, or plateletpheresis (collection and removal of platelets from the circulation). No randomized, placebo-controlled studies have demonstrated a better survival benefit with one therapy over the other. Whether any discrete benefit is gained by also controlling the platelet count remains unclear.

Transfer

Patients undergoing elective splenectomy for splenomegaly may develop significant hemorrhaging during their operation if controlling the splenic hilum proves difficult. Such patients may require abdominal packing and transfer to a tertiary center with personnel who have expertise in angioembolization and splenic resection for splenomegaly. ^[3]

Such centers usually have the additional resources (eg, a well-stocked blood bank, a tertiary level intensive care unit) to support the organ systems in these patients. Multisystem organ failure is not uncommon following severe hemorrhage, and these patients are no exception.

Consultations

Consultation with a hematologist is ideal before surgery for enlarged spleens in order to secure necessary blood products. Postoperative management does not usually require intervention from a hematologist.

The usual postoperative activity restrictions imposed on a patient who has undergone a laparotomy or laparoscopy also apply to patients after a laparoscopic splenectomy.

Patients with uncorrected splenomegaly should be counseled to refrain from contact sports or activities that would predispose them to blunt abdominal trauma. Examples include skydiving, horseback riding, soccer, football, and ice hockey. These restrictions reduce the likelihood that blunt injury will lead to splenic rupture and uncontrolled hemorrhage.

As the majority of cases of splenomegaly are secondary to some underlying disorder, it is incumbent on clinicians to first attempt mitigation of the splenomegaly via treatment of those primary disorders. Broad examples of treatment include the following:

• Chemotherapy for hematologic malignancies
• Antibiotics for infection (with the exception of infection associated with a splenic abscess, which requires surgical intervention)
• Immunosuppression for autoimmune disorders such as rheumatoid arthritis
• Disease-modifying therapy for severe heart failure
• Genetic interventions for congenital abnormalities

Important recent developments in mitigating splenomegaly include the use of the JAK2 inhibitor ruxolitinib in primary myelofibrosis, which results in rapid and pronounced reduction in spleen size. ^[29] Eliglustat, an oral substrate reduction therapy, significantly improved spleen volume, hemoglobin level, liver volume, and platelet count in 40 previously untreated adults with Gaucher disease type 1 in a randomized, double-blind, placebo-controlled study. ^[30]

All patients scheduled for elective splenectomy (either diagnostic or therapeutic) should receive the 23-valent polysaccharide pneumococcal vaccine, menigococcal vaccine, and ​H. influenzae vaccine. Ideally vaccination should occur weeks prior to surgery if it is elective. Antibiotic prophylaxis wtih a penicillin is also indicated particularly in younger children less than 5 years old as they are at higher risk for severe sepsis after splenectomy.

The vast majority of splenectomies are performed using laparoscopic techniques. It is important to remember that splenectomy should largely be reserved for only after non-surgical approaches to mitigating the primary disorder causing the splenomegaly have been utilized and in the event of  emergent traumatic situations where splenic sparing/salvage techniques cannot be safely employed. Laparoscopic splenectomy is safe and is associated with reduced hospital stays. Furthermore, this procedure has a postoperative survival advantage when compared with open procedures. Laparoscopic surgery can be performed even on individuals with massive splenomegaly. (See the images below.) ^{[31, 32]}

A reactive thrombocytosis following splenectomy is common though is not clearly associated with an increased risk of VTE. One cohort calculated the incidence of postsplenectomy secondary thrombocytosis at ~30%. ^[33]  This reactive thrombocytosis typically peaks in 2-3 weeks but can persist for months to years.  ^[34] One prospective cohort study evaluating thrombosis risk after abdominal surgery found splenectomized patients to be at a higher rate of postoperative VTE than other abdominal surgeries however there was no statistical correlation between presence of reactive thrombocytosis and VTE.  ^[35]

An onset of fever several days following splenectomy can be due to a recrudescence of malaria. This should be considered as a cause of fever in patients who have lived in areas commonly associated with malaria and in persons who abuse intravenous (IV) drugs who share needles.

With Plasmodium malariae infection, this may occur decades after the initial infection. Malaria from P vivax (3-7 y) and P falciparum (about 1 y) remain active for shorter intervals after the initial infection.

Fulminant, life-threatening infection represents a major long-term sequela after splenectomy in patients with splenomegaly. Splenic macrophages play a major role in filtering and phagocytizing bacteria and parasitized blood cells from the circulation. In addition, the spleen is a significant source of antibody production.

Overwhelming postsplenectomy infection (OPSI), also known as postsplenectomy sepsis syndrome, begins as a nonspecific, flulike prodrome that is followed by a rapid evolution to full-blown bacteremic septic shock—accompanied by hypotension, anuria, and clinical evidence of disseminated intravascular coagulation—thus making this syndrome a true medical emergency. The subsequent clinical course often mirrors that of the Waterhouse-Friderichsen syndrome, with bilateral adrenal hemorrhages noted at autopsy.

Despite appropriate antibiotics and intensive therapeutic intervention, the overall mortality rate in older published studies of established cases of OPSI varied from 50-70%. Information now suggests, however, that if patients seek medical attention promptly, the mortality rate may be reduced to approximately 10%. Of those patients who die, more than 50% do so within the first 48 hours of hospital admission.

Most instances of serious infection are due to encapsulated bacteria, such as pneumococci (eg, Streptococcus pneumoniae). Because these organisms are encapsulated and the spleen is integral in the removal of opsonized bacteria, affected patients are at increased risk for unimpeded sepsis. Pneumococcal infections account for 50-90% of cases reported in the literature and may be associated with a mortality rate of up to 60%. H influenza type B, meningococci, and group A streptococci account for an additional 25% of infections.

Possible OPSI involving an asplenic individual constitutes a medical emergency. The critical point in management remains early recognition of the patient at risk, followed by subsequent aggressive intervention. The diagnostic workup should never delay the use of empiric therapy. Possible choices of empiric antimicrobial agents include cefotaxime (adult dose of 2 g IV q8h; pediatric dose of 25-50 mg/kg IV q6h) or ceftriaxone (adult dose of 2 g q12-24h; pediatric dose of 50 mg/kg IV q12h). Unfortunately, some penicillin-resistant pneumococcal isolates are also resistant to cephalosporins. If such resistance is suggested, consider using vancomycin.

The precise incidence of OPSI remains controversial. Overall, the most reliable data related to incidence estimate approximately 1 case occurring per 500 person-years of observation. Asplenic children younger than 5 years, especially infants splenectomized for trauma, may have an infection rate of greater than 10%.

Splenectomy performed for a hematologic disorder, such as thalassemia, hereditary spherocytosis, or lymphoma, appears to carry a higher risk than splenectomy performed as a result of trauma. A major contributing factor is the frequent existence of splenic implants or accessory spleens in traumatized patients, although accessory spleens can also be seen as a developmental anomaly.

Prevention

Preventative strategies for OPSI fall into 3 major categories: education, immunoprophylaxis, and chemoprophylaxis.

As previously mentioned, education represents a mandatory strategy in the prevention of OPSI. Asplenic patients should be encouraged to wear a Medi-Alert (Pinellas Park, Fla/Henderson, Nev) bracelet and carry a wallet card explaining their lack of a spleen. Patients should also be aware of the need to notify their physician in the event of an acute febrile illness, especially if it is associated with rigors or systemic symptoms.

Vaccination is also appropriate in the prevention of OPSI. This has best been defined for S pneumoniae. Unfortunately, the most virulent pneumococcal serotypes tend to be the least immunogenic, and evidence indicates that the efficacy of the vaccine is poorest in younger patients, who would be at higher risk. However, under ideal conditions in a healthy, immunocompetent host, the vaccine offers a 70% protection rate.

The pneumococcal vaccine should be administered at least 2 weeks before an elective splenectomy. If the time frame is not practical, the patient should be immunized as soon as possible after recovery and before discharge from the hospital or, at the latest, 24 hours following the procedure.

Most authorities recommend antibiotic prophylaxis for asplenic children, especially for the first 2 years after splenectomy. Some investigators advocate continuing chemoprophylaxis in children for at least 5 years or until age 21 years. However, the value of this approach in older children or adults has never been adequately evaluated in a clinical trial.

Preprocedure prophylaxis

A major concern is antibiotic use in splenectomized patients. Those who have undergone splenectomy should receive antibiotic prophylaxis prior to undergoing procedures associated with a risk of transient or sustained bacteremia. Antibiotics should cover encapsulated organisms and organisms likely to be found at the operative site.