Functional Hyposplenism - Causes, Diagnosis, and Treatment

Introduction

Spleen is considered a vital organ as it protects against infection. In functional hyposplenism (FH), the function of the spleen reduces. The finding of such patients is similar to splenectomized (spleen removed) patients. Clinical manifestations of FH are described under the term post-splenectomy syndrome. In this syndrome, encapsulated microorganism infections are increased. These are life-threatening infections.

In severe cases, thrombocytosis (increased platelet count) occurs, leading to an increased risk of thromboembolic events. These events are life-threatening as blood clots get stuck and cause obstruction. Spleen is a graveyard for red blood cells, but in FH, the removal of non-functional red blood cells from the circulation is affected. So non-functional red blood cells can be seen in peripheral blood in the form of Howell-jolly bodies (basophilic nuclear remnants). Functional hyposplenism may eventually proceed to functional asplenism.

What Are the Causes Associated With Functional Hyposplenism?

The conditions that decrease the body's immunity can cause FH are listed below.

• Autoimmune Disorders: Systemic lupus erythematosus, vasculitis, rheumatoid arthritis.

• Hematologic Disorders: Sickle cell disease, acute leukemia, bone marrow transplantation.

• Hepatic Disorders: Alcoholic liver disease, hepatitis, portal hypertension, primary biliary cirrhosis.

• Gastrointestinal Diseases: Celiac disease, Crohn's disease, ulcerative colitis.

• Circulatory Disorders: Splenic or celiac artery thrombosis, splenic vein thrombosis.

• Infectious Diseases: AIDS.

• Miscellaneous: Sarcoidosis, amyloidosis, total parenteral nutrition.

What Is the Pathophysiology of Functional Hyposplenism?

The exact reason for the development of FH is not known.

• In sickle cell anemia, in which FH is associated, initially, the spleen is enlarged because of excessive red blood cell entrapment.

• In advanced cases, spleen degeneration and atrophy occur. The condition is also known as autosplenectomy.

• When FH occurs in celiac disease, it is considered that it may be due to excessive loss of lymphocytes in the condition through enteric mucosa due to this atrophy of the spleen's reticuloendothelial blockade. Blockage of reticuloendothelial (clearance of particles and forms a part of the immune system) occurs due to circulating immune complexes.

• FH in neoplastic and hematologic disorders is mainly due to tumor cells' infiltration of splenic tissue.

What Are the Clinical Manifestations of Functional Hyposplenism?

In splenectomized patients, overwhelming post-splenectomy infection (OPSI) is encountered. The most commonly responsible microorganisms for OPSI are Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenzae type B, and less widely involved Klebsiella pneumonia, Salmonella Typhi.

Clinical manifestation includes:

• The primary source of infection is not so apparent in such patients.

• Prodromal symptoms are present, which are of short duration and non-specific.

• Encapsulated microorganisms cause massive bacteremia (bacteria in the blood).

• Septic shock with disseminated intravascular coagulopathy (a severe condition associated with abnormal blood clotting) is seen in such patients.

• Mortality rates range from 50 to 70% in such patients.

• Death may occur in a short period, usually within 24 to 48 hours.

• Bilateral adrenal hemorrhage is seen (Waterhouse-Friderichsen syndrome). This condition occurs when adrenal glands fail to function properly.

• There is an increased white blood cell count, and mild thrombosis-like hematological abnormalities are common in patients with FH.

• There is an increased risk of thrombotic events.

How to Diagnose Functional Hyposplenism?

An exact diagnosis is made after proper physical examination, blood investigation, and imaging modality. Confirmation of the diagnosis is also based on microscopic findings and the presence of morphologically abnormal red blood cells in peripheral blood.

Methods of diagnosis are as follows:

1. Howell Bodies Present in Peripheral Blood Smear - RBC nuclear remnants are called Howell-Jolly bodies. The spleen does not eliminate these nuclear remnants due to FH. Instead, they are seen on peripheral blood smears under routine optical microscopy. It appears purple (basophilic) color through Hematoxylin and eosin staining.

2. Pitted Erythrocytes Quantification - For FH diagnosis, it is considered the gold standard. A blood smear's presence of depressions on the RBC surface is called a pit. Not seen in routine peripheral smears but in the use of special equipment applied to optical microscopy.

3. Spleen Scintigraphy Using Technetium-99m - For diagnosing FH in the past, liver and spleen scintigraphy and using Technetium-99m sulfur colloid were used. Suppose the uptake is less than it is suggestive of FH. Nowadays, spleen scintigraphy with heat-damaged Technetium-99m labeled RBC is performed, and it is advantageous as it also helps determine the spleen's spleen function.

4. Immunological Test - Immunological function of the spleen can be determined through new techniques. There is presence of a strong positive correlation between functional splenic volume and the percentage of IgM and CD27 cells in hyposplenic patients.

What Is the Differential Diagnosis Associated With Functional Hyposplenism?

• Amyloidosis (It is a disease where a protein called amyloid gets built up in the organs).

• Bone marrow transplant (It is a procedure that replaces bone marrow with healthy cells).

• Celiac disease (It is an immune reaction that occurs because of intake of gluten).

• Glomerulonephritis (It is an inflammation affecting glomeruli of the kidneys).

• Graves disease (It is an immune disorder resulting in overproduction of thyroid hormones).

• Inflammatory bowel disease (It is characterized by inflammation in the lining of the digestive tract).

What Are the Guidelines for Treatment and Prevention in Patients of Functional Hyposplenism?

• Prevention in patients of FH is mainly done through vaccine and antibiotic prophylaxis. Immunization against Streptococcus pneumonia is the most common cause of severe infections in hyposplenic patients, Haemophilus influenzae type B, and Neisseria meningitidis.

• Annual influenza vaccine is given in splenectomy patients along with antibiotic prophylaxis. For vaccines, a schedule is shown, and it should be followed as per guidance.

• Routine antibiotic prophylaxis is not suggested for all patients of FH, but it is indicated in certain patients.

• Before any antibiotic prophylaxis, resistance to local microorganisms should be taken into consideration so appropriate antibiotic prophylaxis is selected.

• The education of the patient and their family is essential in such cases.

• In case of symptoms, immediate medical help must be provided to reduce the comorbidity.

• Symptoms such as high fever, malaise, and shivering may also develop.

• The patient should always keep a supply of Penicillin or Amoxicillin ready to use a pneumococcal conjugate vaccine, a polysaccharide vaccine that should be given to all at-risk patients.

• It is seen that the percentage of severe infections reduced after immunization with the pneumococcal vaccine.

• Antibody measurements on annual basis levels should be done, and if levels are found to be low, then revaccination should be done.

Conclusion

FH has fatal complications, so proper diagnosis, prevention, and treatment are necessary to prevent further complications. Immunization is a must for patients at risk. Vaccination against pneumococcus should be given to all hyposplenism subjects. Education is essential to reduce complications further and tell them about possible dangers and measures required to take action.