Hematological Manifestations of Celiac Disease

Introduction:

Hematologic manifestations are very commonly seen as a result of autoimmune disorders. Autoimmune disorders are a frequent cause of systemic diseases all over the world. One such autoimmune disorder causing clinical manifestations is celiac disease. Celiac disease primarily affects the gastrointestinal system. However, the disease also affects the circulatory system and causes various hematologic manifestations in the human body.

What Is Celiac Disease?

Celiac disease is a persistent autoimmune disorder that is triggered by the ingestion of foods containing gluten. Once gluten-containing foods are taken, antibodies are produced by the immune system against tissue transglutaminase (tTG), and gliadin is present as a significant component in gluten. These antibodies are key players in the autoimmune response that characterizes celiac disease. The immune system mistakenly identifies gluten as a threat and launches an attack. Tissue transglutaminase is an enzyme also found in the small intestine, and antibodies against it are commonly detected in the blood of individuals with celiac disease. These antibodies contribute to the inflammation and irreversible damage of the intestinal lining (specifically the villi of the small intestine) seen in celiac disease.

How Does Celiac Disease Cause Hematological Manifestations?

Celiac disease is a common autoimmune etiological factor known to cause manifestations within the intestinal tract and extraintestinal organs. The skin, nervous system, and circulatory system are commonly affected due to celiac disease. There are several mechanisms involved in creating hematologic clinical manifestations.

• In celiac disease, the villi in the small intestine are severely damaged irreversibly, causing impairment in the absorption process. Loss of absorption or malabsorption can directly lead to nutritional deficiencies. Nutrients, especially iron, vitamin B12, or folate, are essential for the circulatory system and blood formation. Dysregulation in this process can cause hematological manifestations.

• The autoimmune response triggered in the body occurs for a chronic period. This chronicity can abruptly interrupt the normal hematopoietic processes within the body and contribute to secondary complications.

• Immune-mediated mechanisms may also play a role in conditions like autoimmune hemolytic anemia (antibodies target red blood cells).

• Furthermore, the systemic inflammatory milieu in celiac disease may increase the probability of such individuals to an elevated risk of developing lymphoproliferative disorders, further complicating the hematologic profile.

Thus, hematological manifestations are important clinical aspects that should be adeptly diagnosed and treated.

What Are the Hematological Manifestations of Celiac Disease?

A broad spectrum of diseases affects various blood components in celiac disease. The most common are:

• The most common hematologic manifestation seen commonly in celiac disease is anemia. This is because there is a deficit in iron absorption in the intestine, thus leading to iron deficiency anemia. In some cases, people may have chronic disease anemia due to the systemic inflammation associated with celiac disease. Megaloblastic anemia can also be seen as a result of dysfunctional vitamin B12 and folate absorption from the intestine. Iron supplementation is administered to discern the cause of anemia between celiac disease and other factors. However, anemia persists despite iron supplementation in celiac disease as it also requires treatment of the underlying etiology of celiac disease. This approach aids in distinguishing anemia attributable to celiac disease from other etiologies.

• The immune-mediated process in the body seen in celiac disease also acts against the platelets (thrombocytes) in the body. Thus, platelet destruction and impaired production lead to thrombocytopenia and thrombocytosis (excessive number of platelets) in some individuals. Thrombocytosis also occurs as a result of a dysfunctional spleen (hyposplenism).

• Vitamin K deficiency commonly occurs as a result of celiac disease. This can cause bleeding in people.

• Reduced numbers of white blood cells, especially neutrophils, are observed in celiac disease patients.

• Celiac disease is also associated with an increased probability of lymphoproliferative disorders. The most common is non-Hodgkin lymphoma; in rare cases, Hodgkin lymphoma is seen. Chronic inflammation with aberrant immune response is considered the causative factor for the incidence of lymphoproliferative disorders.

• Due to deficiency and dysfunctional clotting factors, the body's bleeding and clotting mechanisms are altered in celiac disease. The most common bleeding sites are the nose, urinary tract, and mucosa lining the nose and oral cavity.

• Thrombosis, particularly venous thrombosis, is seen in celiac disease. This manifests as diseases like deep vein thrombosis and induces a state of hypercoagulability in the body. Platelet abnormalities, along with increased homocysteine levels and deficient protein S in the blood, are considered to be responsible for the thrombotic events noted in celiac disease.

• Selective IgA deficiency, often associated with celiac disease, can predispose individuals to autoimmune phenomena. One such complication is autoimmune hemolytic anemia.

• The continuous process of autoimmunity in the body of patients with celiac disease can lead to the destruction of the splenic tissue. This can cause changes in the blood parameters and increase the risk of infectious agents, especially those triggered by bacteria with capsules, such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.

How to Manage Hematologic Manifestations of Celiac Disease?

Timely and adept diagnosis is possible when regular laboratory hematological examinations are done to identify any abnormalities at an early stage.

• Since the causative factor for this chronic autoimmunity in the body is gluten, following a gluten-free diet becomes mandatory.

• Adequate nutrients (vitamin B12, iron, and folate) should be supplemented externally to optimize the hematologic parameters.

• Individuals with celiac disease, particularly those with persistent or severe hematologic manifestations, may require screening for associated conditions such as lymphoproliferative disorders.

• In cases of refractory celiac disease or severe autoimmune complications such as autoimmune hemolytic anemia, immunomodulatory therapies (consisting of corticosteroids, immunosuppressants, or other biological agents) may be considered.

• Given the increased risk of thrombotic events in individuals with celiac disease, particularly those with additional risk factors such as immobility or concurrent inflammatory conditions, thromboprophylaxis or anticoagulant therapy may be indicated.

• Patients with hyposplenism should also receive vaccination against infectious agents and antibiotic prophylaxis to curb the incidence of infections.

Conclusion:

The hematologic manifestations of celiac disease represent a diverse spectrum of abnormalities with significant clinical implications. From anemia and thrombocytopenia to lymphoproliferative disorders and autoimmune phenomena, celiac disease can exert profound effects on the hematopoietic system. Research is required to understand the underlying pathophysiology and curate medical treatment accordingly.