The purpose of this study was to examine the different clinical scenarios encountered in patients having an infection and concurrent SI. To this end, we investigated various etiologies in order to elucidate the overall relationship between infection and SI and found that the etiologies were largely divided into i) thrombotic events due to IE or sepsis, ii) events due to the presence of intracellular organism, and iii) events due to synergy of localized infection and other risks.
Thrombogenic events can be considered as the main mechanism underlying infection-induced SI (35.3% in this study). Infection can cause thrombosis by various mechanisms. Under inflammatory conditions, increased cytokine production due to sepsis disrupts the coagulation system , activating platelets by the action of the pro-inflammatory mediators, such as platelet-activating factors , as well as the action of P-selectin, which increases systemic inflammation and leads to platelet adhesion . The functioning of the elements of the anti-coagulation mechanism, including anti-thrombin, the protein C system, and inhibitors of the tissue factor pathway, can be compromised by infection . In IE, vegetation occurs in the damaged endothelium. The degree of adhesion may vary depending on the type of organism involved . The common pathogens involved include Staphylococcus, Streptococcus and Enterococcus as well as other fungal species. The occurrence of antiphospholipid syndrome or disseminated intravascular coagulation in association with severe infection can also be considered a thrombogenic event.
In this study, 27 patients (26.7%) were classified as having miscellaneous systemic infections; the causative pathogens in most of these cases were intracellular organisms. Malaria and babesiosis have previously been shown to cause SI [17, 18]. Both are parasitic diseases in which the parasites infect the red blood cells (RBCs). In these diseases, parasitemia and destruction of RBCs result in hemostasis and cytokine-induced thrombosis, which serve as the main causes of SI; however, the exact mechanism by which SI occurs in these diseases remains unclear. Orientia tsutsugamushi infection was frequently identified in several of our patients. This organism is known to cause endothelial dysfunction, leading to triggering of fibrin formation and platelet adhesion and aggregation by endothelial cells . Additionally, endothelial dysfunction contributes to the impairment of the protein C system . Antiphospholipid syndrome is another cause of endothelial dysfunction . In addition to the conditions revealed in this study, Q fever, herpes infection, brucellosis, typhoid, and murine typhus  are other conditions that cause SI due to endothelial dysfunction. When physicians encounter cases of SI, they must take into consideration the possibility of infection with different pathogens capable of causing endothelial dysfunction. It is worth noting that most of the patients in this group (miscellaneous systemic infection) also have splenomegaly. In addition to endothelial dysfunction, vessel compression accompanying splenomegaly may be considered as one of the causes of splenomegaly, but there are no clear studies on this. Identifying the presence or absence of splenomegaly in SI patients may be helpful in differentiating those patients with intracellular organism from other patients with SI. In addition, the fact that the patients in the miscellaneous systemic infection group did not show multi-organ occlusion can help differentiate them from other SI patient groups.
Most patients with localized infection and SI had at least one risk factor. The following risk factors — trauma, surgery, pancreatitis, pancreatic tumor, and portal vein thrombosis — which were seen at a rate of 11.9% in this study, are generally considered unrelated to infection, except for pancreatic abscess, splenic abscess, and pylephlebitis (liver abscess)[21, 22]. Hematologic malignancy, vasculitis, hypercoagulative status, and atrial fibrillation, however, are thought to lead to splenic infarction because of their varied associations with infection. Hematologic malignancy is thought to be associated with splenomegaly and/or hyperviscosity under acute leukemic conditions. However, infections due to an immunocompromised status should always be monitored, and attention should be paid to the increased tendency of thrombosis due to infections. Patients with connective tissue disorders may develop splenic infarction as a result of vasculitis, splenomegaly, and antiphospholipid syndrome (22). Infections in patients with vasculitis are generally thought to be secondary to an immunocompromised status, but the possibility of infection exacerbating connective tissue diseases should also be taken into consideration . Exacerbation of atherosclerosis due to infection is sometimes ignored in clinical practice. Our findings revealed that atherosclerotic disease was the most common risk factor (22/101, 21.8%) for SI in patients with infection. Several studies have shown that infection exacerbates atherosclerosis . However, acute infection alone is unlikely to cause a rapid enough aggravation of atherosclerosis to cause SI. Other studies suggest that occlusion may be associated with vasospasm. Arterial spasms can be caused by the increased production of the cytokine interleukin-1 and reduced bioavailability of nitric oxide during acute infection (19). In patients with atrial fibrillation, infections can promote SI by enhancing thrombogenic tendencies. Infection can lead to atrial fibrillation, but only two of our patients developed paroxysmal atrial fibrillation, and most patients with atrial fibrillation had had it before.
These above mentioned conditions must be differentiated using various approaches. First, it is important to differentiate between bacteremia and IE. Then, efforts should be made to identify the underlying diseases or risk factors. If no other risk factors are identified, infection by intracellular organisms should be ruled out. In this study, we found that the presence of intracellular organisms was associated with splenomegaly without infarction in other organs. These findings may help differentiate the causes of various SI, but a comprehensive evaluation of the patient’s underlying disease and history is important. Further, it is difficult to make a diagnosis of splenic infarction with a localized infection alone, and, in this case, the doctor must check whether the patient with SI has other risk factors.
Our study has a few limitations. First, this study was a retrospective investigation; however, a prospective study on this topic is difficult to perform because of the nature of SI. To overcome the drawbacks of a retrospective study design, we took into account various risk factors for SI and analyzed their potential correlations for the development of SI. Second, specific pathogen(s) could not be identified in some of the investigated cases. Third, the findings of this study are based on the experience at a single tertiary hospital, and it may be difficult to apply these findings elsewhere, particularly because diseases such as malaria and scrub typhus show significant regional variation in incidence. Nevertheless, the purpose of this study was to examine the nature of the relationship between infection and SI rather than to analyze the exact etiology of SI.