Traumatic injury of the spleen was historically routinely treated with splenectomy. This leads to loss of immunity to encapsulated organisms, in particular streptococcus pneumoniae, and the risk of overwhelming post-splenectomy infection (OPSI) [13] with a mortality rate of 50–70 %. [14]. Moreover splenectomy is associated with other disadvantages including an increased risk of premature death [15].
Today, splenic conservation is preferred with surgery reserved for patients who are haemodynamically unstable or who have other injuries requiring laparotomy. The object of SAE is to improve the rate of splenic conservation in the nonsurgical management group. However, there is very limited evidence that SAE preserves splenic immune function. It is only in recent years that the immune function of the spleen has become better understood and useful assays have become available to evaluate splenic immune function directly.
The immune function of the spleen includes a specific role in the defence against encapsulated bacteria. Production of natural antibody and innate immunity against bacterial infection has been attributed to B1 cells and to IgM Memory B cells which are found in the splenic marginal zone (SMZ) as well as in the peripheral blood, tonsils, and lymph nodes [16, 17]. SMZ B cells require a functional spleen for optimal development and maintenance. The SMZ surrounds the white pulp of the spleen and is farthest away from the central arteriole. It may, therefore, represent a watershed zone which is more vulnerable than other zones to a fall in splenic perfusion pressure.
Around half of the B cells in the blood express the CD27 marker and are considered memory B cells [18, 19]. There are two populations of memory B cells—switched memory B cells and IgM memory B cells. Switched memory B cells produce high-affinity antibodies and protect against reinfection [20].
The role of IgM memory B cells is to respond rapidly to blood-borne polysaccharide antigens expressed by encapsulated bacteria. Upon stimulation, the prediversified IgM memory B cells initiate a T-cell-independent response, rapidly proliferating and differentiating into antigen-presenting cells or into IgM-, IgG- and IgA-secreting plasma cells. Unlike switched memory B cells, IgM memory B cells do not promote long-term protective humoral immune responses but give protection for approximately six months [21]. Deficiency or absence of IgM memory B cells is associated with increased frequency of pneumococcal infections and impaired response to polysaccharide pneumococcal vaccines [16].
IgM memory B cell levels are reduced or absent in splenectomised and asplenic individuals [12, 16, 20, 21]. A significant reduction or absence of IgM memory B cells is also found in patient groups with an intact spleen but known increased risk of invasive pneumococcal infection [18].
The level of circulating IgM memory B cells can therefore be considered to be a marker for splenic immune function, and for the degree of protection against infection and OPSI.
It is important to note that the spleen plays a role in preventing OPSI over and above the role of the SMZ environment for memory B cells. It entraps circulating pathogens during systemic infections. OPSI never occurs in individuals lacking IgM memory B cells but with an intact spleen, such as young children and some CVID patients [19]. This strengthens the case for preserving the spleen by embolisation.
Proximal SAE (PSAE) is performed by occluding the splenic artery just distal to the origin of the dorsal pancreatic artery. The aim of PSAE is to decrease splenic perfusion pressure and thereby increase the likelihood of haemostasis whilst preserving some perfusion of the spleen via collateral vessels [10]. It has been shown to reduce splenic intra-arterial blood pressure by >50 %, albeit in a study involving only 2 patients [22].
Distal embolisation is often used for the treatment of focal vascular injuries such as pseudoaneurysms or arteriovenous fistulae [4, 23]. Subsequent bleeding may occur because some vascular injuries are initially not detected at angiography or CT due to vasospasm [4, 23]. However, a recent meta-analysis found that the only difference in short-term outcomes between the two techniques was a higher rate of splenic infarcts after distal embolisation [10].
As it is currently utilised in the management of blunt splenic trauma, the effect of SAE on splenic function has not been well defined. One other group has reported that IgM memory B cell levels are preserved after SAE [24]. Their study only included 15 patients and they did not specify whether embolisation was proximal or distal.
Other groups have attempted to assess the effects of SAE on splenic immune function using previously available methods.
Bessoud and co-workers reported preservation of antibody responses to polysaccharide antigens in a series of 24 trauma patients who underwent proximal vessel SAE [25]. At 6–63 months after SAE, all of the patients had sufficient exposure-driven immunity against Haemophilus influenzae type b; 94 % had sufficient exposure-driven immunity against Pneumococcus and 83 % had a sufficient response to Pneumococcus vaccination.
Tominaga et al. [26] compared levels of CD3, CD4, CD8 cells, and IgG, IgM, C3 and Compliment Factor B between patients who had undergone combined (proximal plus distal) SAE, controls and splenectomy patients. They found that CD8 levels were significantly higher in the splenectomy group, whilst still within the normal range, but otherwise there were no differences between the three groups.
Neither of these studies, however, was able to measure splenic immune function directly. Our study, complementing that of Skattum et al. [24], has provided direct evidence of the impact of SAE on splenic immune function, and has provided evidence that both proximal and distal embolisation preserve splenic immune function by comparison with splenectomy.
We had hypothesised that distal embolisation would better preserve splenic function than proximal embolisation, since proximal embolisation leads to a global fall in splenic arterial perfusion pressure potentially putting all the splenic marginal zones at risk of infarction, whereas with distal embolisation only the embolised portions of the spleen are affected. Our results did not show a significant difference in IgM Memory B cells between the two groups, but did show a significant difference between the control group and the proximal but not the distal embolisation group. We conclude from this that there was a trend towards significance but that the numbers in the distal embolisation group were too small to prove this.
However both groups maintained IgM Memory B cell levels significantly higher than those in the splenectomy group, confirming that SAE by either method preserves splenic immune function better than splenectomy. In the absence of long-term follow-up data on infections from the splenic registry, it is however not yet possible to say whether or not these patients still require pneumococcal vaccination and antibiotic prophylaxis.
Our study has limitations and our numbers are too small to draw definite conclusions. A significant number of patients were lost to follow-up. Although patients were prospectively enrolled in the study, they were not randomised, and the choice of proximal versus distal embolisation was up to the individual operator. This introduces potential bias, and future studies should randomise patients with injuries where there is equipoise between the two methods. We were obliged to grade splenic injury using the method of Mirvis et al. [13] which does not take into account the degree of vascular injury, rather than the more recent modification of Marmery and Shanmuganathan [8], which differs subtly in that it incorporates splenic vascular injury as Grade IVa. This was because the thin-slice CT data were not archived to the picture archiving and communication system (PACS) in every case.
The SMZs are likely to be the most vulnerable to hypotension as described above. We were unable to control for the degree of hypotension due to blood loss experienced by patients, which is likely to have been most severe prior to the onset of treatment. It may be that hypovolaemic shock can cause damage to the marginal zones even in the absence of splenic trauma. The question of whether global hypotension contributes to hypoperfusion of the SMZs and subsequent loss of IgM Memory B cells could only be answered by an animal study.
In conclusion, our study provides further evidence to support the concept that splenic artery embolisation allows preservation of splenic immune function, and suggests that distal embolisation may better preserve immune function than proximal embolisation. Further research will be necessary to evaluate this hypothesis.