Autoimmune Cytopenias: Cluster of Blood Disorders

What Is Cytopenia and What Are Its Types?

Cytopenia means a low level of certain blood cells in the body, including red blood cells, white blood cells, and platelets. Cytopenia can be classified based on its etiology and the type of blood cells affected in this condition.

Classification of cytopenia related to the underlying cause of the low blood cell count includes -

• Autoimmune Cytopenia - This occurs when a person has an autoimmune condition causing the body's immune system to attack healthy blood cells. This abnormal reaction of the immune system leads to a reduction in the level of one or more blood cells.

• Refractory Cytopenia - This occurs when the bone marrow (spongy tissue present inside some bones that produce blood cells) is not able to produce normal amounts of mature and healthy blood cells.

Classification based on the type of blood cell affected -

• Anemia - Condition with low red blood cell levels leading to a reduction in the amount of oxygen the body receives.

• Leukopenia - Low white blood cell levels. This can make the body more prone to infections.

• Thrombocytopenia - Low platelet levels leading to problems with blood clotting.

• Pancytopenia - Low levels of all blood cell types.

What Is Autoimmune Cytopenia?

Autoimmune cytopenias are a group of disorders in which the hematopoietic cells get destroyed by the immune system of the body. The destruction of hematologic cell lineages occurs in this condition, including white blood cells (neutrophils), red blood cells, and platelets. A single lineage disease means only one type of cell is affected, and it can be characterized by the production of autoantibodies against the body’s cells, such as red blood cells (AIHA - autoimmune hemolytic anemia), platelets (ITP - autoimmune thrombocytopenia), and neutrophils (AIN - autoimmune neutropenia). However, in the case of multilineage disease combination of these conditions may occur.

What Are the Different Autoimmune Cytopenia Conditions?

Autoimmune cytopenia is a type of cytopenia that further include some of the conditions which are explained below -

1. Autoimmune Hemolytic Anemia (AIHA) -

This condition is defined as the destruction of mature red blood cells (RBCs). This is caused by the anti-RBC autoantibodies produced by autoreactive B lymphocytes. The destruction of RBCs by the autoantibodies can occur due to numerous mechanisms such as phagocytosis (destruction) of erythrocytes (red blood cells) by autoantibodies and activated by macrophages (a type of white blood cell). AIHA is usually divided into two types - warm and cold, depending upon the thermal characteristics (reactivity at 37°C or 4°C) of the autoantibody formed.

a) Warm Autoimmune Hemolytic Anemia - This is the most prevalent form of autoimmune hemolytic anemia (AIHA), representing 60 to 70 percent of all cases.

• Clinical Features - Fatigue and jaundice.

• Laboratory Tests -

  • CBC (complete blood count).

  • Reticulocyte count.

  • Bilirubin levels.

  • Lactate dehydrogenase (LDH enzyme blood test).

  • Direct Coomb’s test (to detect antibodies that are present on the surface of red blood cells).

  • Blood smear examination for spherocytes (smaller size round red blood cells).

• Treatment -

  • Steroids.

  • Splenectomy.

  • Erythropoiesis-stimulating agents (ESA).

  • Rituximab.

b) Cold Autoimmune Hemolytic Anemia -

• Clinical features -

  • Fatigue.

  • Jaundice.

  • Passage of brown urine

• Laboratory Tests -

  • CBC (complete blood count).

  • Blood smear examination for agglutination, spherocytes, or erythrophagocytosis (ingestion of red blood cells by macrophages).

  • Direct Coomb’s test (to detect antibodies that are present on the surface of red blood cells).

• Treatment -

  • RBC transfusion.

  • Chlorambucil.

  • Cyclosporine.

  • Rituximab.

Secondary Causes of AIHA -

Autoimmune hemolytic anemia (AIHA) can also occur due to some other conditions, which include -

• Idiopathic.

• Drug-induced such as Cephalosporins, α-methyldopa, Penicillins, and Quinidine.

• Lymphoproliferative disease -

  • Chronic lymphocytic leukemia (cancer of the blood and bone marrow).

  • Non-Hodgkin's lymphoma (a cancer of the lymphatic system).

• Autoimmune disease -

  • Systemic lupus erythematosus or SLE (an autoimmune condition causing widespread inflammation and tissue damage in the affected organs).

  • Autoimmune lymphoproliferative syndrome or ALPS (genetic disorder associated with an excessive number of lymphocytes).

• Infections -

  • Human immunodeficiency virus.

  • Hepatitis B virus (HBV),

• Previous allogeneic blood transfusion.

• Hematopoietic stem cell transplant.

• Organ transplant.

• Immune deficiency such as COVID.

2. Autoimmune Thrombocytopenia (ITP)-

This is an autoimmune condition characterized by an unexplained low platelet count of less than. 20 000 (20x109/L) or lower (normal level of platelets 150,000 to 400,000 per mL or 150 to 400 x109/L of blood) and mucocutaneous bleeding. ITP is classified as acute, in case the duration is six months or longer, and chronic in case the duration is more than six months. The incidence of this disorder in adults is around six new cases per 100,000 per year. This disease is also common in children, with an estimated incidence between 4.0 and 5.3 per 100,000. However, according to various investigations, it has been found that this condition may present at any age in any gender and peaking at the age of five.

Children and adult-onset ITP may present differently. In children, it may lead to sudden onset of purpura or petechiae is seen often followed by a viral illness, and 80 percent of the cases resolve within one year. In adults, onset is insidious, and the disease often takes a chronic course.

Causes -

• Idiopathic.

• Infections such as hepatitis C or HIV.

• Post-vaccination.

• Lymphoproliferative disease:

  • Chronic lymphocytic leukemia (cancer of the blood and bone marrow).

  • Hodgkin's lymphoma and Non-Hodgkin's lymphoma (cancers of the lymphatic system).

  • Large granular lymphocytic leukemia or LGL (rare white blood cell cancer).

Investigations -

• Platelet count.

• Antigen-specific autoantibody assays.

• Blood smear examination to exclude pseudo thrombocytopenia and confirm large platelets.

Treatment -

• Steroids.

• Splenectomy.

• Rituximab.

• Intravenous immunoglobulin (IVIG).

3. Autoimmune Neutropenia (AIN) -

This is a rare group of diseases characterized by the production of IgG autoantibodies against neutrophils, causing phagocytosis and problems with the spleen. AIN can be of two types primary or secondary, depending upon the causative agent. Patients with autoimmune neutropenia may be either entirely asymptomatic or may suffer recurrent infections.

Laboratory testing is required to confirm the diagnosis; once the count of neutrophils is lower than 0.5 × 109/L, the risk of infections is high.

Management of autoimmune neutropenia usually depends upon the patient's age and frequency of infection. This is most common in infants and is self-limiting. If it is associated with other autoimmune conditions, then treatment with the following medications is recommended -

• Steroids.

• Rituximab.

• Intravenous immunoglobulin (IVIG).

Conclusion:

An autoimmune cytopenia is a group of complex conditions, and therefore a correct diagnosis and close observation are of paramount importance in treating these conditions. The incorporation of clinical history and lab investigations plays a key role in the diagnosis of the underlying secondary cause of the condition. After diagnosis, these conditions are easy to manage. They can be treated without any complications, and in some severe cases, the treatment may be intense and of long duration, depending upon the situation.