Aplastic Anemia: Causes, Symptoms, Diagnosis, and Treatment

What is Aplastic Anemia?

Aplastic anemia (AA) is a rare but potentially life-threatening disorder of the hematopoietic system characterized by impaired bone marrow function. In this condition, the bone marrow loses its ability to produce a sufficient number of all three major types of blood cells: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). This leads to pancytopenia—a decrease in the concentration of all formed blood elements in the peripheral blood. The bone marrow becomes hypocellular, meaning it contains few blood-forming cells and is replaced by fatty tissue.

Causes of Aplastic Anemia

In most cases (about 70–80%), the cause of aplastic anemia remains unknown, and this condition is referred to as idiopathic aplastic anemia. It is believed that idiopathic AA is driven by an autoimmune process in which the body's own immune system mistakenly attacks and destroys bone marrow stem cells.

In other cases, AA can be secondary, developing under the influence of various factors:

• Medications: Certain drugs can cause bone marrow suppression. These include chemotherapeutic agents used in oncology, certain antibiotics (such as chloramphenicol), anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), and gold salts.
• Exposure to Toxins: Contact with certain chemicals, such as benzene and its derivatives, insecticides, herbicides, and other organic solvents, can trigger the development of AA.
• Viral Infections: Certain viral diseases can be associated with the development of aplastic anemia. These include viral hepatitis (especially hepatitis C, less commonly B), Epstein-Barr virus, cytomegalovirus, and HIV.
• Autoimmune Diseases: In rare cases, AA may be associated with other autoimmune conditions, such as systemic lupus erythematosus or rheumatoid arthritis.
• Pregnancy: In some women, aplastic anemia may develop during pregnancy, which is thought to be linked to immunological changes in the body.
• Inherited Syndromes: There are genetic disorders that predispose individuals to aplastic anemia. The most well-known is Fanconi anemia, as well as Diamond-Blackfan anemia (although it more commonly presents as pure red cell aplasia) and Shwachman-Diamond syndrome. These conditions are usually diagnosed in childhood.

Symptoms of Aplastic Anemia

The symptoms of aplastic anemia are caused by a deficiency of each type of blood cell:

• Symptoms related to anemia (lack of red blood cells):
  • Persistent fatigue, weakness, and decreased performance.
  • Paleness of the skin and mucous membranes.
  • Shortness of breath, especially during physical exertion.
  • Dizziness and headaches.
  • Rapid heartbeat (tachycardia).
• Symptoms related to leukopenia and neutropenia (lack of white blood cells, especially neutrophils):
  • Increased susceptibility to infections.
  • Frequent bacterial, viral, or fungal infections that can be severe and difficult to treat.
  • Fever of unknown origin.
  • Mouth and throat ulcers, stomatitis.
• Symptoms related to thrombocytopenia (lack of platelets):
  • Easy bruising and hematomas.
  • Petechiae (small pinpoint hemorrhages under the skin) and purpura (larger spots).
  • Nosebleeds (epistaxis) and gum bleeding.
  • Prolonged bleeding from minor cuts or injuries.
  • In severe cases, internal bleeding, including brain hemorrhages, which can be life-threatening.

Diagnosis of Aplastic Anemia

Diagnosing aplastic anemia requires a comprehensive approach and involves several stages:

• Complete Blood Count (CBC): The first step is to detect pancytopenia—a decrease in hemoglobin, red blood cells, white blood cells (especially neutrophils), and platelets. This usually presents as normochromic normocytic anemia, though macrocytosis may also be present.
• Bone Marrow Biopsy: This is a key diagnostic method. A bone marrow sample taken from the iliac bone is examined under a microscope. In aplastic anemia, a hypocellular bone marrow is found, where normal blood-forming cells are replaced by fatty tissue.
• Bone Marrow Aspiration: Often performed simultaneously with a biopsy. It allows evaluation of the cellular composition and helps rule out other conditions such as myelodysplastic syndrome, acute leukemia, or tumor metastasis.
• Ruling out Other Causes of Pancytopenia: It is important to differentiate AA from other conditions that can cause a decrease in all hematopoietic lineages, including:
  • Vitamin B12 or folic acid deficiency (megaloblastic anemia).
  • Systemic autoimmune diseases.
  • Certain infections.
  • Paroxysmal nocturnal hemoglobinuria (PNH), which can develop as a complication or concurrent condition of AA.
• Additional Tests: May include virological tests (for hepatitis, HIV, Epstein-Barr), autoantibody assays, genetic testing (to rule out inherited forms such as Fanconi anemia), and flow cytometry to detect a PNH clone.

Treatment of Aplastic Anemia

Treatment for aplastic anemia depends on the severity of the disease, the patient's age, and the availability of a compatible donor. The goal of therapy is to restore normal hematopoiesis in the bone marrow.

• Supportive Care:
  • Blood Transfusions: Packed red blood cells are transfused for severe anemia; platelet concentrates are given for thrombocytopenia accompanied by bleeding or high risk thereof. To prevent complications, transfused blood is often leukoreduced and irradiated.
  • Antibiotics and Antifungals: Used to treat and prevent infections, especially in the presence of pronounced neutropenia.
  • Growth Factors: Colony-stimulating factors (e.g., G-CSF) can be used to stimulate white blood cell production, but their role in the long-term management of AA is limited.
• Specific Therapy:
  • Immunosuppressive Therapy (IST): The main treatment method for patients who lack a compatible donor for transplantation or for elderly patients. It includes:
    • Antithymocyte Globulin (ATG): A medication that suppresses the immune system, allowing the body's own bone marrow stem cells to recover.
    • Cyclosporine: An immunosuppressant often used in combination with ATG to enhance the effect and prevent rejection.
  • Hematopoietic Stem Cell Transplantation (HSCT): A potentially curative method and the preferred choice for younger patients (typically under 40–50 years old) with severe aplastic anemia who have a fully matched related or unrelated donor. During HSCT, the damaged bone marrow is destroyed using chemotherapy or radiation therapy and then replaced with healthy donor stem cells.
  • Eltrombopag: A thrombopoietin receptor agonist that stimulates platelet production and has been shown to also improve the function of other hematopoietic lineages in some AA patients, especially when combined with IST.

Prognosis and Outlook

The prognosis for patients with aplastic anemia has improved significantly over recent decades thanks to advancements in diagnostic and treatment methods. Without treatment, severe aplastic anemia carries a very poor prognosis. However, with immunosuppressive therapy and, particularly, hematopoietic stem cell transplantation, most patients can achieve remission and lead full lives. Early diagnosis and timely initiation of appropriate therapy are key factors for a successful outcome. Patients require regular medical follow-up to monitor blood counts and timely detect potential complications or relapses.

Sources

Please note: The provided scientific publications do not pertain to the topic of aplastic anemia. Therefore, the article text does not contain source citations [1]–[8] for facts concerning aplastic anemia. These sources are listed here in accordance with the assignment requirements.

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• [3] Acephalgic Migraine Presenting as Episodic Fatigue and Nausea: A Case Report. (Clinical medicine & research, 2025). Acephalgic Migraine Presenting as Episodic Fatigue and Nausea: A Case Report.
• [4] Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia. (JCEM case reports, 2026). Addison-like Clinical Phenotype Without Adrenal Insufficiency: A Rare Manifestation of Pernicious Anemia.
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The information contained in this article is for reference purposes only and should not be used for self-diagnosis or self-treatment. Always consult a qualified medical professional for diagnosis and the selection of an optimal treatment plan.