A 30-year-old male is applying for life insurance. He describes a severe case of infectious mononucleosis complicated by splenic rupture and subsequent splenectomy at the age of 21. Fourteen days after the splenectomy, a series of vaccines was administered.
Regular follow up with his family physician has occurred since then, which included revaccination every five years. The applicant has been in good health, but he did see an urgent care doctor four years ago and was diagnosed with a sinusitis, but he was successfully treated with antibiotics. He was given a prescription for antibiotics to have on hand at home to be used for any future similar infections. His doctor mentions in the note that he counseled the patient regarding the increased risk of severe infections in asplenic patients, including “life threatening sepsis and death”. The Insurance lab is WNL.
What are the mortality considerations for those with a prior history of splenectomy performed for non-malignant reasons?The spleen is an important human organ which has multiple functions. It is involved in the humoral and cellular immunity activities of the human body which help protect from illness. The
spleen removes bacteria as well as damaged red blood cells from the blood stream. It stores platelets and white blood cells. The blood vessels in the spleen can dilate significantly, which allows the storage of extra blood to be used in an emergency. However, the spleen’s presence is not essential for survival, and a splenectomy is sometimes medically necessary for a variety of reasons.
Incidence
Splenectomy occurs in the United States approximately 25,000 times each year. There are over one million people in the US who are living and asplenic.
Mortality implications
There is an increased all-cause mortality associated with undergoing a splenectomy. Perioperative mortality is of concern especially when the splenectomy is performed in an emergency situation.
When the splenectomy was performed as part of the treatment for a malignancy or other serious chronic illness, there is increased mortality associated with the underlying illness. However, even
in those without an underlying severe chronic illness, the lack of a fully functional spleen can independently impact survival (see Table 1).
Table 1: Complications of Splenectomy Reported in the Literature
Pneumonia
| Solid tumors (e.g., colon, liver, lung, prostate)
| DVT
|
Meningitis
| Hematological cancers (e.g., Hodgkin lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma)
| Pulmonary embolism
|
Sepsis
| | Portal vein thrombosis
|
There is a lifelong increased risk of severe bacterial infections, including sepsis. There is also increased risk of developing venous thromboembolism. Finally, several observational studies have shown asplenic individuals to have an increased risk of developing malignancies. This occurs even in those who had the splenectomy performed initially for non-malignant reasons.
Asplenia
Asplenia or relative asplenia is associated with many conditions. Congenital absence of the spleen occasionally occurs, although it’s rare. Surgical splenectomy is performed for life saving treatment of traumatic splenic injuries. Malignant conditions occasionally require splenectomy.
Non-malignant conditions also can occasionally require a splenectomy for treatment. Examples include a variety of hematologic, immunological or infectious conditions (see Table 2).
Table 2: Conditions Associated with Absolute or Relative Need for Splenectomy (Not Inclusive)
| Primary splenic malignancy or splenic involvement of adjacent tumors (e.g., gastric, pancreatic) | Hereditary sphyerocytosis
| Trauma
|
| Hematogical malignancies (e.g., acute leukemia, chronic myeloid leukemia, chronic lymphatic leukemia) | Sickle cell disease
| Spontaneous rupture secondary to infection |
Metastasis
| Immune thrombocytopenic purpura
| Splenic artery aneurysm
|
| | Hypersplenism
| Splenic cysts
|
| | Thalassemia
| Portal hypertension
|
| | Autoimmune hemolytic anemia
| Metabolic storage disorders (e.g,, amyloidosis, Gaucher’s disease) |
Finally, functional asplenia is associated with several conditions such as uncontrolled HIV or chronic graft versus host disease after transplantation.
Infectious mononucleosis as a cause of splenectomy
One of the conditions that can lead to a splenectomy is when an overwhelming infection occurs. Infectious mononucleosis (IM), as seen in this illustrative case, is one of these infectious diseases associated with surgical splenectomy.
IM is frequently associated with splenomegaly (approximately 50-100% of cases). Rarely splenomegaly can lead to splenic rupture (one or two cases per thousand). This rupture can occur spontaneously or can be associated with trauma occurring while the spleen is markedly enlarged.
In fact, when atraumatic splenic rupture occurs, approximately 27% are secondary to infections, with infectious mononucleosis being a prominent cause. The altered architecture of the spleen as well as possible sudden portal venous pressure increases are theorized as etiologic components to the increased incidence of splenic rupture in IM. Conservative non-operative treatment is the
preferred management of splenic rupture, although splenectomy is sometimes required. Splenectomy occurs typically as an emergency operation since splenic rupture can be life threatening.
Mortality concern: infections/sepsis
One of the major mortality concerns in post-splenectomy individuals is sepsis. The spleen is very effective in clearing bacteria from the bloodstream and is imperative to maintaining a highly effective humoral immune system.
Virulent, encapsulated bacteria are more dangerous and more apt to create severe life-threatening illnesses in those without a functioning spleen. In addition, the deficiency of IgM antibodies and depressed T-cell function associated with the absence of a healthy spleen can lead to devastating results from infectious agents.
Mortality can be as high as 50% with sepsis. Sepsis can be very sudden in onset and in some cases can be catastrophically severe with deterioration and death occurring within hours. Because of this, clinicians typically suggest treating febrile illnesses aggressively to avoid this complication. For those individuals who are immunocompromised (e.g., chronic immunosuppressive drug use, HIV, congenital agammaglobulinemia, cancer and transplant
patients) there is an increased risk for severe infections and sepsis.
There are several strategies used to mitigate the risk of infection after a splenectomy (see Table 3). To decrease the chance for contracting these potentially dangerous post-splenectomy
infections, aggressive immunization is recommended.
Table 3: Treatment after Splenectomy
| Pneumococcal - both types (Pneumovax-23 and Prevnar 13) Revaccination every five years
| Prophylactic
| Education
|
| HiB (Haemophilus influenza type B) Revaccination not required
| Early treatment
of febrileillnesses
| Early clinical evaluation after an animal bite, tick bite or any febrile illness |
Meningococcal - both types (MenACQWY and MenB) Revaccination every five years for MenACWY vaccine
| |
|
| Influenza Revaccination every year
| | |
| Tetanus, diptheria, pertussis Routine revaccination
| | |
Zoster
(if 50 years old or older)
| | |
Since most causes of sepsis are from Streptococcus pneumonae (pneumococcus), this organism is especially important to target. However, other bacteria (e.g., Haemophilus influenzae type b (Hib)) and viruses (i.e., influenza) are also targets of immunization. Revaccination is sometimes required.
Unfortunately, immunization is not 100% effective in preventing all cases of infections from the targeted organisms. In addition, other infectious agents (e.g., Escherichia coli, Staphylococcus aureus) have no immunization option. These organisms can be extremely virulent and pose a danger in patients without an intact spleen.
To mitigate the risk for developing the most severe complications of an acquired infection, patients are typically educated on the importance of prompt clinical evaluation when an infection occurs. Urgent care is needed anytime there is a febrile illness or an illness with severe symptoms. Antibiotics are frequently prescribed early in the infectious illness course.
Prophylactic antibiotics are sometimes recommended in certain post-splenectomy patients, especially for those who have had an episode of post-splenectomy sepsis or those in the first one to two years after splenectomy.
Other causes of increased mortality
Although sepsis is the most common illness impacting mortality in asplenic individuals, there have also been reports in the literature of other causes of increased mortality. These includes both thrombotic disease and malignancy.
One study published in 2013 by S. Kristinsson et al in Supportive Care in Hematology evaluated the records from 8,149 cancer-free veterans who underwent splenectomy. Follow-up in this study
occurred for up to 27 years following surgery.
Researchers observed an increased rate of thrombotic disorders (e.g., deep venous thrombosis and pulmonary embolism: rate ratios=2.2).
Researchers also observed an increase in the development of cancer. Certain solid tumors (e.g., buccal, esophagus, liver, colon, pancreas, lung and prostate: rate ratios=1.3-1.9) and hematologic malignancies (e.g., non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia and any leukemia: rate ratios=1.6-3.0) were observed. Risk for these complications was observed even 10 years after the splenectomy.
An increased risk of developing cancer as noted in the Kristinsson et al study has been associated with a splenectomy in other studies as well. However, there are studies which cast doubt on an increased risk of malignancy after splenectomy. For instance, one large study published in 1995 by Mellemkjoer et al in Cancer observed no increased risk of malignancy in the 6,315 trauma associated splenectomized patients. Further studies are needed to evaluate the risk of cancer in splenectomized patients.
The CDC estimates the average risk in the general population for thromboembolic disease to be approximately one to two per 1,000 people per year with an estimated 60,000-100,000
Americans dying annually from this condition. As mentioned above, splenectomized patients are thought to be at increased risk of venous thromboembolism.
While thromboembolic complications can occur in any blood vessel, the risk is especially prevalent in the splenic and venous portal (SPV) system. The risk is highest in the first few months after splenectomy; however, some estimate the risk to remain elevated by threefold a year or more after the procedure.
Returning to the case
This otherwise healthy 30-year-old patient has an interesting history of infectious mononucleosis complicated by a ruptured spleen which required a splenectomy. His family doctor has
identified him as having an increased mortality risk and has initiated several mitigating activities to offset this risk.
He has been vaccinated regularly, has been educated regarding the importance of prompt care for infectious conditions and has had good surveillance. There have been no thrombotic or malignancy complications. He has had occasional infections but has consulted a physician early in the disease and has responded promptly.
Although a history of a splenectomy is associated with an increased mortality risk, there does not appear to be a significantly increased mortality risk in this case.
References
Aldrete JS. Spontaneous rupture of the spleen in patients with infectious mononucleosis. Mayo Clinic Proceedings. 1992;67(9):910.
Asgari MM, and Begos DG. Spontaneous splenic rupture in infectious mononucleosis: a review. Yale Journal Biol Med. 1997;70(2):175.
CDC.gov. https://www.cdc.gov/ncbddd/dvt/data.html Accessed 5/20/2019.
Mellemkjoer, L. et al Cancer risk after splenectomy. Cancer 1995;75: 577-583.
Putukian, M et al. Mononucleosis and Athletic Participation: An Evidence-Based Subject Review. Clin J Sport Med 2008;18:309-315.
Rodeghiero, F et al. Short- and long-term risks of splenectomy for benign haematological disorders: should we revisit the indications? British Journal of Haematology. 2012;158:16-29.
Rubin, L et al Care of the Asplenic Patient. NEJM. 2014;371: 349-56.
Schrier, S et al. Approach to the adult with splenomegaly and other splenic disorders. UpToDate. Last referenced 3-28-2019.
Thomsen, R.W. et al. Risk of venous thromboembolism in splenectomized patients compared with the general population and appendectomized patients: a 10-year nationwide cohort study.
Journal of Thrombosis and Haemostasis, 8:1413-1444.
