Asplenia

Etiology

Asplenia may be congenital, acquired, or functional despite the spleen's anatomic presence. Acquired asplenia most commonly results from trauma or surgical removal. Historically, trauma has been the leading indication for splenectomy.[10] In one retrospective review, the results showed traumatic injury accounted for 41.5% of splenectomies, while hematologic malignancies and cytopenias each accounted for 15.4%.[11]

A range of benign and malignant hematologic disorders may necessitate splenectomy, including hereditary spherocytosis, sickle cell disease, thalassemia major or intermedia, refractory immune thrombocytopenia, myeloproliferative disorders such as myelofibrosis with symptomatic splenomegaly, autoimmune hemolytic anemias, lymphoproliferative disorders, and, rarely, thrombotic thrombocytopenic purpura.[4] Congenital asplenia may occur in isolation or as part of rare syndromes such as Ivemark syndrome, a form of heterotaxy characterized by splenic hypoplasia or absence, complex congenital heart defects, and abnormal thoracoabdominal organ arrangement.[12]

Beyond the common causes of asplenia, numerous additional etiologies have been reported across multiple organ systems. These include the following:

• Gastrointestinal disorders: celiac disease, Whipple disease, and inflammatory bowel diseases [13]
• Infectious diseases: HIV and other acquired immunodeficiency states [13]
• Hepatic disorders: Alcoholic liver disease, cirrhosis, portal hypertension, and hepatorenal syndrome [13]
• Rheumatologic conditions: Systemic lupus erythematosus [4] 
• Chronic graft-versus-host disease: Rare cases reported [14]

Epidemiology

Following splenectomy, the risk of vascular thrombosis varies by underlying disease. Younger individuals face a greater risk of infection, with the highest incidence of complications occurring within the first 2 postoperative years.[15] The epidemiology of asplenia varies by underlying etiology. Nearly all patients with sickle cell anemia (hemoglobin [Hgb] SS disease) develop functional asplenia and are at high risk for overwhelming infection.[13][16] Other hemoglobinopathies, such as HgbSC disease, may also lead to splenomegaly, splenectomy, or progressive splenic dysfunction. Additional conditions associated with reduced splenic function include celiac disease (prevalence 33%–76%), Whipple disease (47%), and alcoholic liver disease (37%–100%).[13] Remark syndrome is rare, occurring in approximately 1 in 10,000 to 40,000 cases.[6] 

Pathophysiology

The pathophysiology of asplenia varies with the underlying disease and comorbid conditions. In many benign hematologic disorders, functional asplenia results from recurrent hypersequestration of RBCs, causing splenic enlargement followed by progressive atrophy. Severe atrophy, or autosplenectomy, is characteristic of sickle cell anemia, particularly in patients with HgbSS disease.[13] In contrast, hematologic malignancies may lead to asplenia through direct infiltration of malignant cells into the splenic parenchyma.

Several gastrointestinal disorders can lead to functional asplenia. In hepatic dysfunction or failure, disruption of normal hepatic circulation, such as in portal hypertension, may contribute to splenic hypofunction. Alcohol use can also exert direct toxic effects on splenic tissue.[13] In celiac disease, excessive lymphocyte loss through the inflamed intestinal mucosa leads to reticuloendothelial atrophy and subsequent functional asplenia.[13] 

Histopathology

Histologically, splenic atrophy is characterized by degeneration of the white pulp, including reduced periarteriolar lymphatic sheaths, follicles, germinal centers, and marginal zones. The red pulp shows diminished hematopoietic elements. Cytologic markers of asplenia include Howell–Jolly bodies and pitted RBCs on peripheral smear, along with nonspecific findings such as monocytosis, lymphocytosis, or thrombocytosis.[17] The presence of “pocked” or highly vacuolated erythrocytes in high proportions, sometimes exceeding 80%, is considered a highly sensitive indicator of hypo- or asplenia.[18] 

History and Physical

Patients with asplenia can be asymptomatic or present with nonspecific symptoms such as malaise, fatigue, fever, or encephalopathy. On physical examination, a normal spleen is not palpable, and in functional asplenia or autosplenectomy, chronic atrophy typically renders the spleen nonpalpable. When enlarged, it can generally be palpated below the costophrenic border on deep inspiration.

Clinical presentations often reflect underlying infection. Severe infections with S pneumoniae, Haemophilus influenzae, and N meningitides are most common, and assessment for nuchal rigidity is essential in febrile individuals. Pneumococcal meningitis is notably more severe in this population, with mortality up to 4 times higher and poor outcomes more than 6 times more likely compared with other bacterial meningitides.[7] Aslepnic patients are also at increased risk for infections such as malaria (Plasmodium falciparum), babesiosis, and Capnocytophaga canimorsus.[19][20] 

Evaluation

Peripheral blood smear evaluation may reveal Howell-Jolly bodies, nuclear remnants within RBCs, which are a key clue to congenital or functional asplenia. To confirm clinical findings and assess splenic anatomy, multiple imaging modalities may be used, including abdominal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and splenic scintigraphy.[6] Ultrasound, CT, and MRI can further characterize congenital or vascular abnormalities. Spleen scintigraphy, which uses a technetium-99m–labeled radiocolloid taken up by splenic tissue, demonstrates absent uptake in patients with asplenia. 

Treatment / Management

Patients with asplenia are at markedly increased risk for severe bacterial infections, particularly those caused by encapsulated organisms. Accordingly, preventive strategies, early detection, and prompt management have become central to care in this population. S pneumoniae is the most common pathogen, with one study reporting infection rates of up to 87% in patients with asplenia.[21] 

To reduce morbidity, all patients with asplenia, regardless of the cause, should receive appropriate vaccinations against encapsulated bacteria. Immunization is recommended before and after splenectomy, and individuals with functional asplenia or autosplenectomy should follow the same comprehensive vaccination schedule. Before planned splenectomy, patients should receive the pneumococcal conjugate vaccine (PCV13) at least 8 weeks prior, followed by the pneumococcal polysaccharide vaccine (PPSV23), the Haemophilus influenzae type b conjugate vaccine (Hib), and the quadrivalent meningococcal conjugate vaccine at least 14 days before surgery.[7] Continued booster doses for pneumococcal and meningococcal vaccines are also recommended.[19]

Vaccination should continue in the postoperative period. Five years after splenectomy, patients should receive a repeat dose of PPSV-23, with an additional dose recommended at age 65. The meningococcal conjugate vaccine should be administered every 5 years.[22] In patients with acquired immunodeficiency, assessment of vaccine titers may help determine immune status. Annual influenza vaccination is also advised.

Prophylactic penicillin is recommended for children with asplenia, such as those with sickle cell disease, until age 5, but is not routinely recommended for adults.[23] Adults with asplenia should, however, have immediate access to antibiotics from their healthcare provider, as delays in treatment can be life-threatening.[7] Individuals aged 50 and older should receive the recombinant zoster vaccine, and COVID-19 vaccination is strongly recommended.[9][19](A1)

Overwhelming post-splenectomy infection occurs most frequently in children younger than 16 years, reflecting immune immaturity.[13] Patients with asplenia presenting with signs of infection should receive immediate broad-spectrum antibiotics pending identification of the causative microorganism. According to the Surviving Sepsis Campaign guidelines, antimicrobial therapy should be initiated within 1 hour of suspected sepsis to reduce adverse outcomes.[23] 

Prompt intravenous fluid resuscitation is essential, with escalation to vasopressors for hemodynamic support as needed. Mechanical ventilation may be required in cases of respiratory failure. Emerging resistance to beta-lactam and macrolide antibiotics has been reported.[16] Despite optimal management, mortality from overwhelming sepsis in asplenic patients remains high, approaching 40% to 50%.(B3)

Differential Diagnosis

The differential diagnosis of asplenia includes hyposplenia, which shares many clinical features and may precede progressive functional decline or autosplenectomy. Unlike asplenia, hyposplenia may be reversible with treatment of the underlying condition. For example, in patients with celiac disease, improved disease control can restore normal splenic function.

Prognosis

The prognosis of asplenia is poor if unrecognized, as affected patients face a substantially increased risk of severe infection in the absence of appropriate vaccination. Vaccination and, in selected cases, antibiotic prophylaxis are key management strategies, particularly for individuals with asplenia and concomitant immunodeficiency.[13] Patients who remain unimmunized are at high risk of severe bacterial infection, sepsis, septic shock, and death. Fatal infections may occur despite optimal medical care. Accordingly, patient and caregiver education is essential. In patients with asplenia, early recognition of infection and prompt communication with healthcare providers are critical, as delays in treatment can be life-threatening.[16]  

Complications

The most common and serious complication in patients with asplenia is overwhelming post-splenectomy infection (OPSI). Asplenia confers increased susceptibility to infections caused by encapsulated organisms, most notably S pneumoniae. OPSI is characterized by rapid-onset, massive bacteremia, often without an identifiable primary source, a brief prodromal phase, and progression to septic shock that may be complicated by disseminated intravascular coagulation. Mortality rates of 60% to 70% have been reported in inadequately treated cases.[13]

In the normal spleen, the red pulp filters blood and removes senescent erythrocytes through phagocytosis, providing defense against intraerythrocytic parasites.[24] Loss of this function predisposes patients with asplenia to parasitic infections, including babesiosis and malaria. The white pulp contains organized T- and B-cell compartments that support adaptive immunity and antibody production, including a significant population of memory B cells, which are essential for humoral immune responses.[24] The absence of memory B cells in individuals with asplenia contributes to more severe infections. Additionally, the spleen serves as a reservoir for noncirculating, undifferentiated monocytes within the red pulp, which are mobilized in response to myocardial injury and contribute to tissue repair. Splenectomy eliminates this monocyte reserve, potentially impairing wound healing.[25]

Beyond its immunologic functions, the spleen contributes to vascular homeostasis, and asplenia has been associated with thrombotic complications. Vascular events have been reported most frequently in patients with hematologic disorders such as beta thalassemia, in whom thrombotic events occur in approximately 1.65%.[26] Increased rates of stroke, myocardial infarction, and coronary artery disease have also been observed.[27] These complications are thought to arise from chronic inflammation and endothelial dysfunction, leading to platelet activation and thrombosis.[24]

Asplenia is also associated with pulmonary hypertension, likely related to an increased thrombotic risk. The reported incidence ranges from 8% to 11.5% and is substantially higher in patients with hemoglobinopathies, reaching up to 30% in those with sickle cell disease or beta thalassemia.[24][28] Additional severe complications include adrenal hemorrhage, known as Waterhouse–Friderichsen syndrome, and purpura fulminans.[29] Both conditions require a high index of clinical suspicion, as early recognition and prompt management are essential to reduce morbidity and mortality.