Giuseppe Leone1 and Eligio Pizzigallo2
1Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma. 2Università “G. d’Annunzio”, Chieti. (Italy)
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Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram-negative (G-) bacteria. The underlying disease is the most important factor in determining the frequency and severity of infections. So, splenectomy for malignant diseases has the major risk of infections.
A 73-year-old man, affected by
splenic lymphoma with massive splenomegaly underwent to elective
splenectomy at seventy. He has been suffering from splenic lymphoma for
ten years and on therapy with Chlorambucil and Rituximab; the
indication for splenectomy was an enormous spleen resistant to chemo -
immunotherapy and a mild thrombocytopenia. He received the 23-valent
pneumococcal polysaccharide vaccine (PNEUMOVAX 23) after surgery that
he repeated two years later. Three years after his surgery, he calls
his primary care doctor because he has fever and cephalgia. What is the
appropriate management? Patients splenectomized for a hematologic
disease are at major risk than subjects splenectomized for trauma?
Which prophylactic measures and which therapy are indicated?
Splenectomy, while often necessary in otherwise healthy patients after major trauma,[2-3] find its primary indication for patients with an underlying malignant or nonmalignant hematologic diseases (Table 1).[2-12] Rarely spleen rupture can occur spontaneously, more frequently in a pathological spleen for infectious or/and hematologic diseases[13-17] and in patients on anticoagulation. People without risk factors or previously diagnosed disease can, even if rarely, undergo to splenic rupture for minor trauma o if treated with high dose of growth factors for stem cell harvest. Furthermore, functional asplenia, due to auto infarction, frequently develops in subjects with sickle cell anemia Also, hyposplenism states are common in patients with chronic graft-versus-host disease after stem-cell transplantation, severe celiac disease, and untreated human immunodeficiency virus infection.
Table 1. Causes of splenectomies in different series.
Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools (Figure 1,2). Reduction of splenectomy is even more evident after trauma since splenic preservation has become a well-reported and accepted principle.[8,21] Splenectomy for cancer staging is infrequently performed, and no longer requested for Hodgkin Disease (HD) staging, as in the past,. The introduction of rituximab has reduced the necessity of splenectomy for some lymphoproliferative diseases, hemolytic anemia and ITP. At present the splenectomy sometimes can also be avoid by treating resistant ITP patients with thrombopoietin-receptor agonists.[12,23] All these data infer that the indications for splenectomy continue to evolve, with a progressive reduction, more evident after trauma and in malignant hematologic diseases.
|Figure 1. Number of splenectomy throughout the recent years.|
|Figure 2. Number of splenectomy throughout the recent years.|
splenectomy, even if with different modalities including laparoscopic
splenectomy and partial splenectomy,[24,25] continue to be a current
surgical practice. Approximately 25,000 surgical splenectomies are
performed annually in the United States; and, the total number of
asplenic persons in the United States is currently estimated at 1
million, including 70,000 to 100,000 persons with sickle cell
disease. Data in the other countries are not available. In clinical
practice splenectomy is performed worldwide for different reasons
according to the prevalence of different pathologies, circumstances and
availability of drugs, found in every country (Table 1).
In high-income countries, like USA, Australia, Europe at present, the proportion of splenectomy secondary to trauma represents the 15-30% of all cases (Table 1).[2,5,7,8] This percentage is lowering, Some years ago (2001) Bisharat reported a percentage of splenectomy due to trauma in 50% of adults and 30% of children. However, in high-income countries there is a clear decrease over calendar time in the incidence of splenectomy for all indications except nonmalignant hematologic diseases (Figure 1 and 2).
In the low-income country and war period, the proportion of trauma splenectomy could be higher.
Khamechian report in Iran a percentage of 75% of trauma splenectomy and Deodhar report similar results in India (Table 1).
Among the non-traumatic splenectomy hematologic indications are prevalent but differ in the various countries and the different series. In Europe and USA the prevalent indications of splenectomy are represented by the lymphoproliferative diseases (more frequently in the hospitals with prevalent oncological patients, such as the Memorial Sloan-Kettering Cancer Center, New York, USA and by the ITP (more frequently in the General Hospitals, as reported by two important series of American College of Surgeons and by the Swedish Study. In Asia and in Africa hemoglobin disorders are the prevalent indication for splenectomy (Table 2).[30,31]
|Table 2. Percentage of splenectomy in the different hematologic pathologies, according different countries and times.|
Programmed splenectomy is made more and more frequently by
laparoscopy, which is mostly utilized for benign spleen-related
diseases.[24,32] However at variance with European and USA experience,
in the Chinese and Asian series, portal hypertension and hypersplenism,
secondary to cirrhosis is an important cause of splenectomy.[32,33] The
study of Wang et Coll. retrospectively reviewed 302 consecutive
patients who underwent laparoscopic splenectomy. 65% of patients had a
benign spleen-related disease, 14% a malignant spleen-related disease
and 21% portal hypertension. In a similar Italian series portal
hypertension does not appear as cause of splenectomy.
Complications of Splenectomy
InfectionsCommonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients.[2-8] They can produce a serious fulminant illness, called overwhelming post-splenectomy infection (OPSI), that carries a high mortality rate.[4,8,36,37,38] However, in the years, the bacterial pattern of splenectomy sepsis have been changing. The most important capsulated pathogen is Streptococcus pneumoniae (Str. Pneumoniae), but Haemophilus influenza (H. Influenzae) and Neisseria meningitidis (N. meningitidis) are also significant. In a study of 1991, reporting 349 episodes of sepsis in patients with asplenia, 57% of infections and 59% of deaths were caused by Str. pneumoniae. Furthermore, 6% of infections were caused by H. influenzae, with a mortality rate of 32%; N. meningitidis was the organism in 3.7% of cases in the same study. Today, after the introduction of vaccination, and oral penicillin antibiotics, patients submitted to splenectomy can suffer from disparate strains of bacterial infection, which are not strictly correlated with the splenic function. In fact, particularly in the post-intervention phase, the type of bacteria isolated in the blood is not so different from those found in other abdominal interventions. So, gram- bacteria are prevalent (51% in the Australian report).[6,8,38] At present in vaccinated patients, the rate of sepsis by pneumococcus is very low. In fact, encapsulated bacteria, such as pneumococcus, meningococcus, and H. influenzae, were rarely encountered in Australian and Danish cohort Series,[6,11,38] in whom vaccination was routinely adopted.
Early InfectionsInfections related to splenectomy can occur early in direct association with intervention (post-operative infectious complications) and late in connection only with the reduced immunological defense induced by splenectomy. Infective complications account for most of the perioperative morbidity and include lower respiratory tract infections, intra-abdominal collections, wound infection and non-specific infections requiring antibiotics.[5-10] The Danish series reports 3812 persons who underwent splenectomy from 1996 to 2005. The maximum relative risk of infection and death was within the first 90 days of intervention, attaining a RR of about 20 fold higher in all indication groups than in the general population comparisons, whereas odds ratios in comparison with appendicectomized patients ranged from 1.0 to 12.7.
|Figure 3. Relative risk of infections after splenectomy with different matchings.|
Late InfectionsPATIENTS SPLENECTOMIZED AFTER TRAUMA WITHOUT A PREVIOUS PATHOLOGY.
Overwhelming Post-Splenectomy Infection (OPSI)
|Table 3. Rate of severe infections in patients splenectomized for different diseases.|
Prevention of infections in patients with an absent or dysfunctional spleen
|Table 4. Dose and time administration of Vaccines.|
Splenectomy, even if the
incidence of OPSI is reducing in high-income countries for the
widespread pneumococcal vaccination, also represent today's an
important risk factor for infections. The introduction of conjugate
vaccines also in the older population could induce a further reduction
of sepsis from encapsulated bacteria. The case reported at the incipit
of this review presented meningitis with a culture of liquor positive
for Str. pneumoniae. The
addition of a conjugate vaccine could have increase the immunological
response reducing the risk of infection. In the high-income countries,
the antipneumococcal vaccination is adequate, at least in terms of
primary vaccination with Pneumovax, but conjugate vaccines have not
been introduced so far in most of the countries. In contrast,
vaccination against N. meningitidis serogroups A + C was insufficient
and introduction of vaccination against B serotype is warranted. There
is a need to improve the awareness among healthcare professionals of
the greatly increased risk of severe infection with encapsulated
bacteria post-splenectomy and how these infections, in particular,
overwhelming post-splenectomy infection, can be prevented. However, at
present gram- negative sepsis are prevalent. Further work is required
to characterize these infections and determine whether or not they were
related to asplenia.
OPSI continue to be described in 1-1.5 patients/year also in vaccinated patients, but Streptococcus pneumoniae, which was in the past the major cause of morbidity and mortality among such patients, has become infrequent as a cause of infections, at least in European series. Poorly controlled iron overload can be the cause of Gram-negative infections that are still frequently diagnosed in post-splenectomy patients for congenital hemoglobin disorders. This information needs to be taken into account when a splenectomized patient presents with fever and/or sepsis. At the first indication of systemic infection (high fever) all patients should have access to primary care and start urgent treatment with appropriate antibiotics, (in general treatment with a third generation cephalosporin, either alone or in combination with other antibiotics that are active against Gram-negative pathogens, should be promptly initiated in order to save the patient’s life). In patients taking prophylaxis treatment should be from an antibiotic class likely to be non-cross resistant. Choice of antibiotic should be made concerning appropriate microbiological advice and local protocols. The importance of the primitive disease remains fundamental in determining the rate and the severity of infections and the overall survival.