Overwhelming Post-Splenectomy Infection: A Case Report With Cause and Manner of Death Considerations

INTRODUCTION

The spleen is a visceral organ in the abdomen that serves both immunologic and hematologic functions. It is the largest collection of lymphoid tissue in the body. It is often prone to trauma, particularly in blunt force injuries of the abdomen (1). As the presence of the spleen is not essential for survival in human beings, it may be removed in association with trauma, as well as for non-traumatic causes. With its removal, the immunologic functions of the spleen are lost, and infection with encapsulated organisms is occasionally observed (2).

Overwhelming post-splenectomy infection (OPSI), formerly known as post-splenectomy sepsis, is a clinical syndrome occurring in patients following removal of the spleen. OPSI was first described in children in the early 1950s by King and Schumacker (3). It was subsequently observed in adults following splenectomy. The clinical course is fulminant, frequently fatal, and typically involves infection by encapsulated bacterial pathogens (4). Encapsulated bacteria are covered with a polysaccharide layer that provides protection from host immune systems. Streptococcus pneumoniae is implicated about half of the time. Together, Haemophilus influenza, Neisseria meningitidis, and group A streptococcus account for an additional 25% of cases (4,5). Encapsulated organisms such as these are particularly resistant to phagocytosis and, following splenectomy, these organisms have the opportunity to thrive in the absence of opsonization and phagocytosis by splenic macrophages.

Although strict diagnostic criteria for OPSI are not available, it is frequently characterized by a viral-like illness followed by an emerging septic clinical picture necessitating hospitalization and emergent medical therapy (4). Death frequently occurs within several hours. OPSI most frequently occurs shortly after splenectomy (often within 2 years); however, later examples occurring more than 10 years after splenectomy have been described (6–10), including up to over 50 years (11). While some series describe increased duration since splenectomy as protective, others do not describe a decline in risk with time elapsed (11–13).

CASE REPORT

A 44-year-old, Caucasian man with a past medical history of splenectomy, abdominal incisional hernia repairs (complicated by small bowel obstruction), and remote alcohol abuse with pancreatitis, presented to the hospital after his girlfriend found him unresponsive. The day prior to being found unresponsive, the decedent had experienced worsening myalgias, as well as vomiting and general “flu-like” symptoms. Review of medical history found that splenectomy had been performed for blunt impact injuries related to a motor vehicle crash 18 years prior to presentation. No history of other potentially immunocompromised conditions was known. No documentation was found regarding the decedent having received a pneumococcal vaccine in the interval since splenectomy.

On presentation, the decedent was noted to be febrile (39.7°C), tachycardic, tachypneic, and hypotensive. The patient was only responsive to deep pain and had a mottled appearance. Petechiae of the skin were noted in addition to hemorrhagic blisters of the oral mucosa. Laboratory studies revealed a metabolic acidosis (with elevated lactate), decreased fibrinogen with elevated D-dimer, thrombocytopenia with increased international normalized ratio (INR). Laboratory evidence of acute kidney and liver injury was also present. The electrocardiogram was unremarkable except for tachycardia, and diagnostic imaging revealed an interstitial lung pattern with hepatic enlargement and steatosis. The decedent was emergently intubated, which was complicated by a period of cardiac arrest of approximately 3 minutes duration prior to the return of spontaneous circulation.

The clinical picture was consistent with disseminated intravascular coagulation/sepsis, and the decedent experienced refractory shock through routine resuscitative measures. He was transferred to a tertiary care facility where his shock persisted despite advanced therapeutic interventions, including inotropic support. Blood cultures collected at the original hospital grew Streptococcus pneumoniae in two of two culture bottles. Despite broad-spectrum antibiotic coverage and vigorous cardiopulmonary support measures, the decedent expired approximately 29 hours after admission to the hospital. Given his history of remote trauma and clinical diagnosis of overwhelming postsplenectomy infection, he was referred to the Medical Examiner's Office for further investigation and certification. The degree to which prior splenectomy contributed to susceptibility for sepsis could not be further elucidated in this case beyond the temporal relationship of the splenectomy to terminal septic presentation. The patient demonstrated no other risk factors for pneumococcal sepsis.

The cause of death was certified as overwhelming postsplenectomy infection (streptococcal sepsis) following remote splenectomy for the treatment of blunt impact abdominal injuries. The manner of death was listed as accidental.

DISCUSSION

OPSI is a clinical syndrome that occurs in individuals who have previously undergone splenectomy for any indication and subsequently develop a fulminant septic clinical picture, often with fatal outcome within 24–48 hours of the onset of symptoms. Strict diagnostic criteria are not well-established, but the estimated prevalence of OPSI following splenectomy is less than 1% (with higher rates reported in children), with a mortality of up to 50%–70% (4). The lifetime risk of OPSI in all patients following splenectomy is estimated to be 5% (12). Infection is characterized by encapsulated bacterial organisms, with Streptococcus pneumonia being the most frequently encountered, although additional organisms have also been described (12). The clinical course is marked by a hyperdynamic cardiovascular state with refractory shock, which ultimately results in circulatory collapse and death.

Disseminated intravascular coagulation (DIC) and purpura fulminans are well-described complications of severe pneumococcal infection, which may occur even in immunocompetent individuals with normal splenic function (14). Streptococcus pneumoniae can produce fulminant sepsis with multiorgan failure, as in our patient, but there are traditionally characteristic cutaneous findings as well. Another differential diagnosis to consider would be DIC and multiorgan failure due to Capnocytophaga canimorsus (15). As such, discerning social history and contact with cats or dogs could help determine etiology.

In the present case, the decedent had a splenectomy 18 years prior to presentation. Although this length of time is longer than average (with most fatalities being reported within the first few years after splenectomy), it is not absent from the literature (5,8–11). The decedent's laboratory studies on presentation were consistent with sepsis, and subsequent blood cultures were positive for pneumococcus. No discrete focus of infection was identified, although the chest radiograph suggested a potential pulmonary origin. The cause of death was recorded as overwhelming post-splenectomy infection (streptococcal sepsis) based on these factors as well as the general clinical impression of the decedent's treating physicians.

The death was referred to the Medical Examiner's Office because of the clinical diagnosis of OPSI and the history of splenectomy for previous trauma. This referral was appropriate as OPSI, by its very name, implies the role of the splenectomy in the fatal chain of causation. The time interval between splenectomy and OPSI would, then, be irrelevant in the establishment of a proximate cause of death in keeping with standard forensic practice (16).

Regardless of the time elapsed between splenectomy and OPSI, it may be argued that the link between OPSI and splenectomy is tenuous and the role of splenectomy in the proximate causation of death is questionable. It is true that the vast majority of patients who undergo splenectomy do not develop OPSI and, conversely, encapsulated bacteria are capable of producing fatal, fulminant, septic courses in the absence of splenectomy (17). While this objection is valid, we argue that it is predicated on the misinterpretation of an intermediate cause of death (sepsis) as a proximate cause, when it is well-established that sepsis has multiple etiologies and OPSI is one. It is true that fatal pneumococcal sepsis has been well-documented in immunocompetent individuals, which does complicate causal attribution in individual cases, but it cannot be ignored that OPSI is classically associated with asplenia. Laboratory or clinical evidence of the patient's baseline immune function prior to death would be helpful to draw a more definitive conclusion, but these are potentially not available in many cases. To dismiss the contribution of splenectomy to a fatal infection with sepsis in the absence of this information would be pedantic.

Further, the fact that most splenectomy patients do not develop OPSI is no reason to discount the well-established immunologic functions of the spleen in response to encapsulated bacteria, and the increased incidence of OPSI in patients following splenectomy can be reasonably assumed to result from the loss of these functions. It is worth noting that, in addition to OPSI, splenectomy is associated with an increased risk of infection in general (18). In addition to the well-established risk of infection with encapsulated organisms, post-splenectomy patients may also be at increased risk for severe infection from tick-borne pathogens, including babesiosis or anaplasmosis. These infections may follow a more severe clinical course in asplenic individuals due to impaired clearance of the intraerythrocytic organisms. Thus, asplenic susceptibility to these organisms further complicates attribution of causation, as there are multiple potential culprits for the sepsis. Identifying the infectious etiology via laboratory testing and/or record review can help bolster certainty with the cause and manner of death determinations.

The rarity of OPSI may prompt the certifier to seek other significant conditions that may have resulted in this clinical picture, but we recommend that all OPSI deaths be reported to the appropriate medicolegal death investigation agency for additional historical review and potential certification. Many splenic injuries will be accidental (e.g., falls, motor vehicle crashes, etc.) and can be designated as such. In instances where splenectomy was performed as a consequence of injury inflicted upon the decedent either by themselves or by another person, consideration of manners of death as suicide or homicide, respectively, should be seriously considered.

A final point for consideration is the OPSI deaths following splenectomy for non-traumatic causes (e.g., sickle cell disease, congenital red blood cell abnormalities, etc). Here, the death investigation agency may opt to refer these cases back to the reporting institution for certification of cause with natural manner. In jurisdictions where the manner of death of “therapeutic complication” is available, responsibility for certification should be accepted by the medicolegal authority, as this would be the most appropriate manner of death designation. The underlying cause of death would be the indication for splenectomy, and mention of the splenectomy in the cause of death statement would be in keeping with accepted practice in this manner of death designations (19). It would not be appropriate in any circumstance to consider the mere passage of time as an indication to exclude the underlying cause of splenectomy for manner of death considerations.

CONCLUSION

OPSI is a frequently fatal, rare condition observed in patients with variable intervals of time between the removal of the spleen and the terminal infection. The rapid clinical decline may prompt referral of the death to the medicolegal authority, but we recommend referrals of all such cases, as the proximate cause of death may be obscure and ultimately prove to be unnatural for purposes of death certification. Investigation into the indication for splenectomy should clarify these issues.