OVERVIEW

What is aplastic anemia?

A blood system disorder caused by various factors leading to weakened or failed bone marrow hematopoietic function, resulting in deficiencies of certain critical blood components. This manifests primarily as anemia, bleeding, recurrent infections, and related symptoms.

The medical definition of this condition is: bone marrow hematopoietic failure characterized by reductions in one, two, or all three peripheral blood cell lineages—erythroid (hemoglobin, red blood cells, reticulocytes), myeloid (neutrophils, monocytes), and megakaryocytic (platelets).

Is aplastic anemia common?

Overall, aplastic anemia is a rare disease. Studies show its incidence is significantly higher in Asian countries than in Europe and America, with males more affected than females. In China, the incidence is approximately 7.4 cases per million people, predominantly chronic aplastic anemia.

SYMPTOMS

How to Detect Aplastic Anemia Early?

Be alert to the possibility of aplastic anemia if the following conditions occur frequently:

• Petechiae on the skin or bruising easily after minor bumps;
• Unexplained nosebleeds;
• Increased menstrual flow in women;
• Recurrent infections in the respiratory, digestive, or urinary systems;
• Pale complexion, fatigue, weakness, and reduced physical endurance.

Note that not all patients will exhibit these symptoms simultaneously—some may only show a few.

Why Does Aplastic Anemia Cause Bleeding?

In aplastic anemia, bone marrow failure leads to a significant reduction in platelet production. Since platelets are essential for clotting, patients experience bleeding symptoms such as skin petechiae, nosebleeds, or heavy menstrual bleeding.

Why Are Infections Common in Aplastic Anemia?

Due to bone marrow failure, the production of immune cells in the blood decreases sharply, weakening the body’s ability to fight infections.

Additionally, severe anemia further compromises immunity, resulting in recurrent, hard-to-control infections.

How Is Aplastic Anemia Classified?

It is generally divided into acute and chronic aplastic anemia:

• Acute Aplastic Anemia: Rapid onset and progression, short course. Anemia may be mild initially but worsens over time, with poor response to transfusions. Bleeding and infections dominate, affecting nearly all patients at diagnosis (also called Severe Aplastic Anemia Type I).
• Chronic Aplastic Anemia: Slow onset and progression, prolonged duration. Anemia is the primary symptom, often improving with transfusions. If symptoms worsen to match acute cases, it’s termed Severe Aplastic Anemia Type II.

Is Aplastic Anemia Dangerous? What Is the Mortality Rate?

Aplastic anemia is life-threatening, especially the acute form. Without prompt treatment, most patients succumb to severe, uncontrolled infections, bleeding, or anemia. Early mortality for acute cases reaches ~15%. Chronic cases progress slower but may transform into acute aplastic anemia, becoming critical.

What Diseases Can Aplastic Anemia Cause?

Complications are numerous, difficult to treat, and often fatal. They include disease-related effects and treatment side effects:

• Disease-related complications:
  • Uncontrolled anemia, bleeding, and infections;
  • Clonal disorders (e.g., progression to myelodysplastic syndrome or leukemia).
• Treatment-related risks:
  • Severe immunosuppression from therapy, worsening infections;
  • Post-transplant rejection (e.g., hemorrhagic cystitis);
  • Clonal disorders after combined immunosuppressive therapy.

CAUSES

What Causes Aplastic Anemia?

Aplastic anemia is primarily caused by genetic factors and acquired factors after birth:

• Genetic factors: Less common, caused by congenital chromosomal abnormalities, DNA defects, and other genetic factors;

• Most cases are due to acquired factors after birth, including drugs, physical, chemical, biological, and immune factors;

• Drug factors: The most common external causative agents, including gold salts, antithyroid drugs, nonsteroidal anti-inflammatory drugs, etc.;

• Physical factors: Such as ionizing radiation;

• Chemical factors: Certain harmful chemical agents;

• Biological factors: Commonly viral infections, with known causative viruses including hepatitis virus and rubella virus;

• Immune factors: May occur secondary to immune system disorders such as systemic lupus erythematosus and rheumatoid arthritis;

• In clinical practice, over half of patients have no identifiable cause, classified as idiopathic aplastic anemia.

Is the Onset of Aplastic Anemia Age-Related?

Aplastic anemia has two peak onset age groups: 5–25 years and over 60 years.

DIAGNOSIS

What tests should be done to diagnose aplastic anemia?

Aplastic anemia is diagnosed based on clinical manifestations, blood tests, bone marrow examination, etc. The most important tests for diagnosis include complete blood count (including reticulocyte count), bone marrow aspiration or biopsy. For infants, children, or patients suspected of congenital aplastic anemia, chromosomal testing should also be performed.

What is a bone marrow examination?

Normal bone marrow is the environment where blood cells proliferate and grow. The "infancy, childhood, and adolescence" stages of blood cells appear in appropriate proportions within it. A bone marrow examination involves extracting bone marrow tissue through aspiration, processing it, and then magnifying the cellular components under a microscope to display them as images. This helps assess bone marrow proliferation and detect any abnormalities.

Since bone marrow is the primary hematopoietic organ, its disorders can directly affect blood composition in blood vessels, making it a crucial test for diagnosing hematologic diseases.

What are the blood test findings in aplastic anemia?

To diagnose aplastic anemia at the first visit, at least two of the following three criteria must be met:

• Hemoglobin < 100 g/L;
• Platelets < 50 × 10⁹/L;
• Neutrophils < 1.5 × 10⁹/L.

These three criteria are the basic conditions for diagnosing aplastic anemia, but diagnosis cannot rely solely on them. A doctor must combine clinical manifestations and bone marrow examination results for confirmation.

What are the bone marrow findings in aplastic anemia?

In aplastic anemia patients, blood cells at various growth stages are reduced to varying degrees or even completely absent.

• Acute aplastic anemia bone marrow findings include:

• Hypocellularity in multiple sites: Bone marrow hypoplasia in two or more aspiration sites.

• Trilineage hematopoietic cell reduction: Decreased erythroid lineage (producing reticulocytes, red blood cells), myeloid lineage (producing white blood cells, neutrophils, monocytes), and megakaryocytic lineage (producing platelets).

• Bone marrow cellularity < 25% of normal.

• If bone marrow cellularity is < 50% of normal, hematopoietic cells should be < 30%.

• (2) Chronic aplastic anemia bone marrow findings show reduction in one, two, or all three lineages (erythroid, myeloid, megakaryocytic), with at least one site of hypoplasia.

What are the related or similar diseases to aplastic anemia?

These include leukemia, paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), Fanconi anemia, etc. Differential diagnosis mainly relies on bone marrow examination to assess proliferation, hematopoietic cell ratios, and abnormal hematopoiesis. Genetic testing may be required if necessary.

TREATMENT

How is aplastic anemia treated?

The treatment of aplastic anemia is mainly divided into supportive therapy and targeted therapy.

• Supportive therapy: This can be considered "symptomatic treatment," primarily aimed at preventing and managing complications caused by anemia, leukopenia, or thrombocytopenia, such as anemia, bleeding, and infections. Treatment methods include:

• Blood transfusion: For example, red blood cells, platelets, or granulocytes can be transfused to correct anemia, thrombocytopenia, and granulocytopenia, respectively.

• Use of immunomodulators: These can enhance immunity and improve the body's resistance.

• Proper daily care to reduce the risk of infections and bleeding.

• Targeted therapy: This can be considered "root treatment," aiming to replenish and replace damaged hematopoietic stem cells and improve bone marrow hematopoietic function. Main treatment methods include bone marrow transplantation, combined immunosuppressive therapy, and androgen combined with cyclosporine intervention therapy.

What is hematopoietic stem cell transplantation?

Hematopoietic stem cell transplantation, also known as bone marrow transplantation, involves the intravenous infusion of hematopoietic stem cells—the "seeds" that produce blood cells—to rebuild the patient's normal hematopoietic and immune systems. Hematopoietic stem cells can be sourced from bone marrow, mobilized to peripheral blood by hematopoietic factors, or obtained from umbilical cord blood. These stem cells can all be used to reconstruct the hematopoietic and immune systems. Patients who respond poorly to conventional treatments (such as drugs or surgery) usually require hematopoietic stem cell transplantation.

What are the types of hematopoietic stem cell transplantation?

• Autologous hematopoietic stem cell transplantation: The stem cells come from the patient's own bone marrow or peripheral blood. (Normally, there are no hematopoietic stem cells in peripheral blood. Special methods are used to release stem cells from the bone marrow into the peripheral blood, which are then collected through cell technology.)
• Syngeneic hematopoietic stem cell transplantation: Transplantation between identical twins.
• Allogeneic hematopoietic stem cell transplantation: Transplantation between parents, siblings, or unrelated donors.

What is the most important condition for aplastic anemia patients undergoing bone marrow transplantation?

The most critical condition for aplastic anemia patients undergoing bone marrow transplantation is successful matching, meaning the HLA compatibility between the recipient and the hematopoietic stem cell donor, with minimal or no rejection.

What are HLA and HLA matching?

HLA (human leukocyte antigen) is a glycoprotein located on chromosomes. This glycoprotein is genetically controlled and uniquely expressed in each individual, serving as a distinctive "identity" marker. HLA matching means that the glycoprotein representing the donor's "identity" is similar or identical to that of the recipient, allowing acceptance without rejection.

How effective is hematopoietic stem cell transplantation for treating aplastic anemia?

Currently, hematopoietic stem cell transplantation is the most effective method for completely curing aplastic anemia, with successful matching being the most critical condition for transplantation success.

• For matched sibling donor transplants (identical twins, siblings, or parents), the 5-year survival rate in major domestic and international hematology treatment centers exceeds 90%.
• For matched unrelated donor transplants, the efficacy is poorer, with a long-term survival rate of about 30%. This option is currently only considered for patients who fail immunosuppressive therapy and lack a matched sibling donor.

What is immunosuppressive therapy for aplastic anemia?

It refers to the use of chemical or biological agents targeting specific antibodies to suppress abnormal immune responses in the body. In other words, drugs are used to inhibit abnormal immune reactions, allowing normal immune responses to function effectively.

What are the immunosuppressive therapies for aplastic anemia?

• ATG + CsA combined immunosuppressive therapy is the standard regimen for severe aplastic anemia, involving anti-lymphocyte globulin (ALG)/anti-thymocyte globulin (ATG) combined with cyclosporine A (CsA).

• For non-severe aplastic anemia, androgen and/or cyclosporine intervention therapy is primarily used in China.

How effective is ATG+CsA therapy for aplastic anemia?

For patients lacking HLA-matched sibling donors, older patients at high transplant risk, or those unable to afford the high treatment costs, hematopoietic stem cell transplantation may not be an option. In China, most severe aplastic anemia patients receive immunosuppressive therapy, with a 1-year survival rate of about 80%, 2-year survival rate of about 70%, and 3-year survival rate of about 60%.

How long does the treatment for aplastic anemia last?

The duration of treatment depends mainly on the therapeutic response. Patients who do not meet clinical cure criteria require long-term medication until the criteria are met. For patients undergoing hematopoietic stem cell transplantation, long-term use of anti-rejection drugs is necessary based on disease progression.

Is hospitalization mandatory after aplastic anemia diagnosis?

Whether hospitalization is required depends on the severity of the condition:

• Newly diagnosed patients with severe infections, bleeding, anemia, or those undergoing combined immunosuppressive therapy or hematopoietic stem cell transplantation should be hospitalized.
• Patients in stable condition without severe complications generally minimize hospital stays to prevent nosocomial infections.

How should aplastic anemia patients choose transfusion therapy?

• Patients with severe anemia, serious infections, high bleeding risk, or active bleeding must receive transfusions.
• For chronic aplastic anemia patients, long-term anemia and thrombocytopenia reduce adverse reactions to hypoxia and low coagulation. If hemoglobin >60 g/L, no severe infection, platelet count >30×10^9/L, and no bleeding, transfusions may be avoided, but close monitoring and care are essential.
• Patients preparing for hematopoietic stem cell transplantation should minimize transfusions. If necessary, irradiated blood (specially treated to reduce impact on stem cell transplantation) is preferred.

Can aplastic anemia be completely cured?

Aplastic anemia is a disease that can potentially be cured with standardized treatment, though further research is needed on its pathogenesis and treatment options.

Non-severe cases have a relatively better prognosis, but challenges include long treatment duration, varied responses to therapy, complications, and possible relapse. Advances in bone marrow transplantation have improved outcomes for some severe cases.

Additionally, a small percentage of non-severe aplastic anemia patients may experience spontaneous remission.

What are the criteria for curing aplastic anemia?

• Resolution of anemia and bleeding symptoms.
• Hemoglobin ≥120 g/L for males and ≥100 g/L for females.
• White blood cell count ≥4×10^9/L.
• Platelet count ≥80×10^9/L.
• No relapse after 1 year of follow-up.

What is bone marrow suppression in aplastic anemia?

Bone marrow suppression refers to abnormal hematopoietic function caused by drugs, radiation, etc. It is common after chemotherapy or radiotherapy. Chemotherapy drugs target rapidly dividing tumor cells but also affect normal tissues like bone marrow and hair follicles. Bone marrow suppression leads to reduced blood cell production, causing anemia (low red blood cells), infections (low white blood cells), and bleeding (low platelets). Severe cases can be fatal due to infections or bleeding. Therefore, chemotherapy patients require regular blood tests to monitor for bone marrow suppression, with treatment adjustments if needed.

DIET & LIFESTYLE

What should aplastic anemia patients pay attention to during outpatient maintenance treatment?

• Patients receiving outpatient maintenance treatment must take medications on schedule. The main medications for non-severe aplastic anemia patients are cyclosporine and/or androgens. Regular monitoring of cyclosporine levels, blood counts, and liver/kidney function is required as directed by the doctor;
• Strengthen care, maintain environmental hygiene, and reduce infection risks;
• Promptly address dental caries and acne that may occur during treatment, and prevent infections;
• Seek immediate medical attention if fever, skin bleeding spots, or bruising appear.

PREVENTION

How to Prevent Aplastic Anemia?

Since aplastic anemia results from a combination of genetic and environmental factors, there is no 100% guaranteed method to prevent it.

Maintaining a healthy diet, exercising regularly, and avoiding exposure to toxic chemicals and ionizing radiation can help reduce the risk of aplastic anemia.