Aplastic anemia Flashcards
What is aplastic anemia?
Aplastic anemia (AA) is a life-threatening form of bone marrow failure. AA refers to pancytopenia in association with bone marrow hypoplasia/aplasia, most often due to immune injury to multipotent hematopoietic stem cells. The term “aplastic anemia” is a misnomer because the disorder is characterized by pancytopenia rather than anemia alone.
Pancytopenia:
- Neutropenia
- Thrombocytopenia
- Anemia
What is the etiology of aplastic anemia?
AA is associated with loss of hematopoietic stem cells (HSC) → Bone marrow cell damage, normal cells are replaced by fat.
- Idiopathic in > 50% of cases: Possibly immune-mediated.
- Medication side effects: carbamazepine, methimazole, NSAIDs, chloramphenicol, propylthiouracil, sulfa drugs, cytostatic drugs (esp. alkylating agents and antimetabolites).
- Toxins: benzene, cleaning solvents, insecticides, toluene.
- Ionizing radiation.
- Viruses: parvovirus B19, HBV, EBV, CMV, HIV.
- Fanconi anemia. Hereditary disease (autosomal recessive) leading to bone marrow failure.
What is the epidemiology of aplastic anemia?
AA is a rare disorder. Half of cases of AA occur in the first three decades of life.
What are some clinical manifestations of aplastic anemia?
The patient with AA most commonly presents with recurrent infections due to neutropenia, mucosal hemorrhage or menorrhagia due to thrombocytopenia, or fatigue, pallor and cardiopulmonary findings associated with progressive anemia.
- Infections are typically bacterial, including sepsis, pneumonia, and urinary tract infection; invasive fungal infection is a common cause of death, especially in patients with prolonged and severe neutropenia.
- Other patients are asymptomatic and present with abnormal blood counts.
What do CBC and peripheral blood smear show?
Complete blood count reveals pancytopenia (ie, neutropenia, thrombocytopenia, and anemia) along with reticulocytopenia.
Neutropenia < 0,5 x 109 /L
Platelets < 20 x 109 /L
The peripheral blood smear typically reveals normocytic red blood cells, but they may be macrocytic (ie, mean cell volume >100 fL). Abnormal cells (eg, myeloblasts, atypical lymphoid cells) are not present unless there is an associated hematologic disorder.
How do you diagnose aplastic anemia?
Diagnostic criteria: AA is defined as pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate or marrow fibrosis.
CBC:
- Pancytopenia (in contrast to aplastic crisis characterized by anemia only)
- Normocytic or macrocytic anemia
- Reticulocyte count: low
- EPO level: high
Bone marrow biopsy findings:
- Hypocellular fat-filled marrow (dry bone marrow tap)
- RBCs normal morphology.
Can be classified into severe, very severe and non-severe AA based on the neutrophil count, platelet count, and reticulocyte count.
What is the treatment approach?
- Cessation of the causative agent. Examples are some medications, or treatment of an infection.
- Supportive therapy (management of cytopenia)
- Treatment of infections (antibiotics, antifungal or antiviral in some cases)
- Blood transfusion
- Platelet transfusion - Bone marrow stimulants (e.g., GM-CSF) in some cases. Erythropoietin in some cases.
- Immunosuppressive therapy. Used to prevent further autoimmune marrow destruction.
- Cyclosporine: often used together with Antithymocyte globulin (ATG), or antilymphocytic globulin. (often used)
(- Tacrolimus)
(- Eltrombopag)
(- Alemtuzumab (Anti-CD52 agent that suppresses T cells).) - Consider hematopoietic cell transplantation (HCT) in young patients. Good option in patients without a cause below the age of 50 years. If no donor start the immunosuppressive therapy (ATG+cyclosporine produces overall response rates of approximately 60 to 80%)
Allogeneic transplantation:
- Brother or sister, best if a twin,
- HLA system compatible family donor.
- HLA system compatible non-family donor.
