Overview

Aplastic anemia occurs when the bone marrow - the spongy tissue inside bones responsible for blood cell production - becomes damaged and can't make enough blood cells. The term "aplastic" means the marrow is empty or contains very few blood cells, while "anemia" refers to low red blood cell counts.

This condition affects people of all ages but has two peak incidences: in children and young adults (15-25 years) and in adults over 60. The disorder affects approximately 2-4 people per million annually in Western countries, with higher rates reported in Asia. While rare, aplastic anemia is a medical emergency requiring prompt diagnosis and treatment.

The severity of aplastic anemia varies from mild to very severe. In severe cases, the extremely low blood cell counts can lead to life-threatening complications including severe infections, uncontrolled bleeding, and heart failure. With modern treatment approaches, including stem cell transplantation and immunosuppressive therapy, many patients can achieve long-term remission or cure.

Symptoms

The symptoms of aplastic anemia result from the deficiency of all three types of blood cells. The presentation can be gradual or sudden, and severity varies based on blood cell counts.

Symptoms from Low Red Blood Cells (Anemia)

Symptoms from Low White Blood Cells (Leukopenia)

  • Fever - often recurrent or persistent
  • Frequent or severe infections
  • Infections that don't respond well to treatment
  • Unusual infections from normally harmless organisms
  • Slow healing of cuts and wounds

Symptoms from Low Platelets (Thrombocytopenia)

Additional Symptoms

Causes

Aplastic anemia occurs when the bone marrow is damaged and can no longer produce adequate blood cells. This damage can result from various causes, though in many cases, the exact cause remains unknown (idiopathic).

Acquired Causes (Most Common)

Autoimmune Disorders: The most common cause in Western countries. The immune system mistakenly attacks and destroys bone marrow stem cells. This accounts for 60-70% of cases and responds well to immunosuppressive therapy.

Toxic Chemicals:

  • Benzene and petroleum products
  • Pesticides and insecticides
  • Industrial solvents
  • Some cleaning products

Medications:

  • Chemotherapy drugs
  • Chloramphenicol (antibiotic)
  • Gold compounds (for rheumatoid arthritis)
  • Anti-seizure medications
  • Some psychiatric medications

Viral Infections:

  • Epstein-Barr virus (EBV)
  • Hepatitis viruses
  • Parvovirus B19
  • HIV
  • Cytomegalovirus (CMV)

Radiation and Chemotherapy: High-dose radiation or chemotherapy for cancer treatment can damage bone marrow. This is usually temporary but can be permanent in some cases.

Inherited Causes

Fanconi Anemia: The most common inherited cause, involving defective DNA repair mechanisms. Usually diagnosed in childhood with associated physical abnormalities.

Other Inherited Syndromes:

  • Dyskeratosis congenita
  • Shwachman-Diamond syndrome
  • Diamond-Blackfan anemia
  • Congenital amegakaryocytic thrombocytopenia

Other Causes

  • Pregnancy: Rare cases of pregnancy-associated aplastic anemia
  • Paroxysmal nocturnal hemoglobinuria (PNH): Can evolve into aplastic anemia
  • Thymoma: Thymus gland tumors
  • Idiopathic: No identifiable cause (30-40% of cases)

Risk Factors

While aplastic anemia can affect anyone, certain factors increase the risk of developing this condition:

Environmental and Occupational Factors

  • Chemical exposure: Workers in industries using benzene, pesticides, or solvents
  • Radiation exposure: Nuclear plant workers, radiologic technicians
  • Agricultural workers: Exposure to pesticides and herbicides
  • Laboratory workers: Handling toxic chemicals

Medical History

  • Previous chemotherapy or radiation: For cancer treatment
  • Autoimmune disorders: Lupus, rheumatoid arthritis
  • Recent viral infections: Especially hepatitis, EBV, or parvovirus
  • Blood disorders: PNH or myelodysplastic syndromes

Genetic Factors

  • Family history: Of aplastic anemia or related disorders
  • Genetic syndromes: Fanconi anemia carriers
  • Asian ancestry: Higher incidence in some Asian populations
  • Age: Peak incidences in teens/young adults and over 60

Other Risk Factors

  • Pregnancy: Rare association
  • Certain medications: Long-term use of specific drugs
  • Male gender: Slightly higher incidence in males

Diagnosis

Diagnosing aplastic anemia requires comprehensive evaluation to confirm bone marrow failure and rule out other causes of pancytopenia. Early and accurate diagnosis is crucial for appropriate treatment.

Initial Evaluation

Medical History: Detailed assessment of symptoms, medication use, chemical exposures, recent infections, family history of blood disorders, and previous cancer treatments.

Physical Examination: Checking for signs of anemia (pallor), bleeding (bruises, petechiae), infection, enlarged organs, and physical abnormalities suggesting inherited syndromes.

Blood Tests

Complete Blood Count (CBC):

  • Low red blood cells (anemia)
  • Low white blood cells (leukopenia)
  • Low platelets (thrombocytopenia)
  • Low reticulocyte count (young red blood cells)

Additional Blood Tests:

  • Blood smear examination
  • Liver and kidney function tests
  • Vitamin B12 and folate levels
  • Iron studies
  • Viral studies (hepatitis, HIV, EBV, parvovirus)
  • Autoimmune markers
  • Flow cytometry for PNH

Bone Marrow Examination

Bone Marrow Aspiration and Biopsy: The definitive test for aplastic anemia. Shows:

  • Markedly reduced cellularity (empty marrow)
  • Increased fat cells replacing blood-forming cells
  • Absence of abnormal cells (ruling out leukemia)
  • No fibrosis or infiltration

Severity Classification

Based on blood counts and marrow cellularity:

  • Non-severe: Does not meet criteria for severe
  • Severe: Marrow cellularity <25% plus two of:
    • Neutrophils <500/μL
    • Platelets <20,000/μL
    • Reticulocytes <20,000/μL
  • Very severe: Meets severe criteria plus neutrophils <200/μL

Additional Tests

  • Chromosome breakage test: For Fanconi anemia
  • Telomere length measurement: For dyskeratosis congenita
  • HLA typing: If transplant is considered
  • Imaging studies: Chest X-ray, ultrasound for organ assessment

Treatment Options

Treatment for aplastic anemia depends on the severity of the condition, the patient's age, overall health, and availability of a matched donor. The goal is to restore bone marrow function and manage complications.

Supportive Care

Essential for all patients while awaiting definitive treatment:

Blood Transfusions:

  • Red blood cell transfusions for severe anemia
  • Platelet transfusions for bleeding or very low counts
  • Use irradiated, leukocyte-reduced blood products
  • Minimize transfusions if transplant is planned

Infection Prevention and Treatment:

  • Prophylactic antibiotics and antifungals
  • Prompt treatment of fevers and infections
  • Isolation precautions when neutrophil count is very low
  • Good hygiene and dental care

Growth Factors:

  • G-CSF (granulocyte colony-stimulating factor) for severe neutropenia
  • Erythropoietin (limited effectiveness)
  • Thrombopoietin receptor agonists (investigational)

Definitive Treatments

Hematopoietic Stem Cell Transplantation (HSCT):

  • Treatment of choice for young patients (<40 years) with matched sibling donor
  • Cure rates: 80-90% with matched sibling donor
  • Alternative donor options: matched unrelated, haploidentical, cord blood
  • Conditioning regimens vary based on age and donor type
  • Risks: graft-versus-host disease, rejection, infections

Immunosuppressive Therapy (IST):

  • First-line for patients without matched donor or age >40
  • Standard regimen: Anti-thymocyte globulin (ATG) + cyclosporine
  • Response rates: 60-70% at 6 months
  • May add eltrombopag (TPO agonist) to improve response
  • Requires 3-6 months to see response
  • Risk of relapse: 30-40%

Treatment Algorithm

For Severe/Very Severe Aplastic Anemia:

  • Age <40 with matched sibling: HSCT
  • Age <40 without matched sibling: IST or matched unrelated donor HSCT
  • Age 40-70: IST first-line, consider HSCT if IST fails
  • Age >70: IST with dose modifications

Emerging Therapies

  • Eltrombopag as first-line with IST
  • Alemtuzumab (alternative to ATG)
  • Haploidentical transplantation advances
  • Gene therapy for inherited forms
  • Novel immunosuppressive combinations

Long-term Management

  • Regular monitoring of blood counts
  • Screening for clonal evolution (PNH, MDS, AML)
  • Iron chelation if multiple transfusions
  • Hormone replacement therapy if needed
  • Psychological support

Prevention

While many cases of aplastic anemia cannot be prevented, especially inherited forms and idiopathic cases, certain measures can reduce the risk of acquired aplastic anemia:

Chemical and Environmental Safety

  • Avoid benzene exposure: Use protective equipment in industrial settings
  • Limit pesticide exposure: Use alternatives when possible, wear protective gear
  • Proper ventilation: When using solvents or chemicals
  • Follow safety protocols: In laboratories and industrial workplaces
  • Regular monitoring: For workers in high-risk occupations

Medication Safety

  • Use medications known to cause aplastic anemia only when necessary
  • Regular blood count monitoring when on high-risk medications
  • Inform doctors of any blood disorders before starting new medications
  • Consider alternatives to chloramphenicol and other high-risk drugs

Infection Prevention

  • Hepatitis vaccination (A and B)
  • Practice safe sex to prevent HIV and other infections
  • Good hygiene to prevent parvovirus and other infections
  • Prompt treatment of infections

Genetic Counseling

  • For families with inherited bone marrow failure syndromes
  • Prenatal testing available for some conditions
  • Sibling testing if family member diagnosed
  • Consider HLA typing of family members

When to See a Doctor

Aplastic anemia can be life-threatening, so prompt medical attention is crucial when symptoms develop. Early diagnosis and treatment significantly improve outcomes.

Seek Immediate Medical Attention For:

Emergency Symptoms Requiring Immediate Care:

  • Severe bleeding that won't stop
  • High fever with severe neutropenia
  • Confusion or altered mental status
  • Severe chest pain or breathing difficulty
  • Signs of stroke (sudden weakness, speech problems)
  • Severe headache with visual changes

Schedule an Appointment If:

  • Family history of aplastic anemia or related disorders
  • Exposure to chemicals or radiation
  • Taking medications associated with aplastic anemia
  • Persistent minor symptoms (mild fatigue, occasional bruising)
  • Need for genetic counseling

Related Conditions

Several conditions may present similarly to or occur alongside aplastic anemia:

Frequently Asked Questions

Is aplastic anemia cancer?

No, aplastic anemia is not cancer. It's a bone marrow failure syndrome where the marrow stops producing blood cells. However, some patients may develop blood cancers like leukemia later, and treatments may be similar to cancer therapies.

Can aplastic anemia be cured?

Yes, aplastic anemia can be cured, especially with stem cell transplantation from a matched donor. Cure rates are highest (80-90%) in young patients with matched sibling donors. Immunosuppressive therapy can also lead to long-term remission in many patients.

Is aplastic anemia hereditary?

Most cases (80-85%) are acquired and not hereditary. However, inherited forms like Fanconi anemia do exist. If you have aplastic anemia, genetic testing can determine if it's inherited, which is important for family planning and sibling screening.

What is the life expectancy with aplastic anemia?

With modern treatment, many patients have normal or near-normal life expectancy. Young patients who receive successful transplants are often cured. Even with immunosuppressive therapy, 5-year survival rates exceed 80% for those who respond to treatment.

Can I work or go to school with aplastic anemia?

This depends on your blood counts and treatment phase. During severe neutropenia, you may need to avoid crowds and sick contacts. Many patients return to normal activities once blood counts improve with treatment. Your healthcare team will provide specific guidelines.

What foods should I avoid with aplastic anemia?

When neutrophil counts are low, avoid raw or undercooked meats, eggs, unpasteurized dairy, raw vegetables, and fruits that can't be peeled. A low-bacteria diet may be recommended during severe neutropenia. Iron-rich foods are generally encouraged unless you have iron overload from transfusions.

References

  1. Killick SB, et al. (2023). Guidelines for the diagnosis and management of adult aplastic anaemia. British Journal of Haematology.
  2. DeZern AE, Churpek JE. (2023). Approach to the diagnosis of aplastic anemia. Blood Advances.
  3. Peffault de Latour R, et al. (2022). Diagnosis and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program.
  4. Young NS. (2023). Aplastic Anemia. New England Journal of Medicine.
  5. National Heart, Lung, and Blood Institute. (2023). Aplastic Anemia and Myelodysplastic Syndromes.