This document discusses aplastic anemia, a condition characterized by pancytopenia and bone marrow hypocellularity. It defines aplastic anemia, discusses its causes (acquired from things like radiation, drugs, viruses, immune diseases, or inherited genetic syndromes), epidemiology, pathophysiology, clinical features including symptoms and examination findings, diagnostic testing including blood tests and bone marrow biopsy, and treatment options including hematopoietic stem cell transplantation, immunosuppression, supportive care, and prognosis.

1. - Dr Rahul Arya
- Assistant Professor
- Department of Medicine

2. DEFINATION
• Aplastic anemia is pancytopenia with bone marrow hypocellularity.

3. CAUSES
Acquired
1. Secondary
i. Radiation
ii. Drugs and chemicals- Benzene, allopurinol, leflunomide, gold, etc
iii. Viruses
a. Epstein-Barr virus
b. Hepatitis (non-A, non-B, non-C hepatitis)
c. Parvovirus B19
d. HIV-1 (AIDS)

4. iv. Immune diseases
a. Eosinophilic fasciitis
b. Hyperimmunoglobulinemia
c. Large granular lymphocytosis (LGL)
d. Thymoma/thymic carcinoma
e. Graft-versus-host disease in immunodeficiency

5. v. Paroxysmal nocturnal
vi. hemoglobinuria (PNH)
vii. Pregnancy
viii. Idiopathic

6. Inherited
i. Fanconi anemia
ii. Dyskeratosis congenital
iii. Shwachman-Diamond syndrome
iv. Amegakaryocytic thrombocytopenia
v. Familial aplastic anemias

7. EPIDEMIOLOGY
• Men and women are affected with equal frequency.
• The age distribution is biphasic, with the major peak in the teens and
twenties and a second rise in older adults.

8. PATHOPHYSIOLOGY
• Bone marrow failure results from severe damage to the
hematopoietic cell compartment.
• In aplastic anemia there is replacement of the bone marrow by fat.
• Early hematopoietic cells, Committed and primitive progenitor cells
are virtually absent.
• An intrinsic stem cell defect exists for the constitutional aplastic
anemias.

9. CLINICAL FEATURES- HISTORY
• Aplastic anemia can appear abruptly or insidiously.
• Bleeding is the most common early symptom
• Easy bruising, oozing from the gums, nose bleeds, heavy menstrual flow,
petechiae.
• Symptoms of anemia are also frequent, including lassitude, weakness, shortness
of breath, and a pounding sensation in the ears.
• Patients often feel and look remarkably well despite drastically reduced blood
counts.

10. • Prior drug use, chemical exposure, and preceding viral illnesses must
often be elicited.

11. Physical Examination
• Pallor
• Petechiae, ecchymoses, retinal hemorrhages.
• Lymphadenopathy and splenomegaly are highly atypical of aplastic
anemia.

12. LABORATORY STUDIES
 Blood
• large erythrocytes and a paucity of platelets and granulocytes.
• Mean corpuscular volume (MCV) is commonly increased.
• Reticulocytes are absent or few, and lymphocyte numbers may be
normal or reduced.

13.  Bone Marrow
• The bone marrow is usually readily aspirated but dilute on smear, and
the fatty biopsy specimen may be grossly pale on withdrawal.
• In severe aplasia, the smear of the aspirated specimen shows only red
cells, residual lymphocytes, and stromal cells.
• Biopsy shows mainly fat under the microscope, with hematopoietic
cells occupying <25% of the marrow space.

14. TREATMENT
 HEMATOPOIETIC STEM CELL TRANSPLANTATION
• This is the best therapy for the younger patient with a fully
histocompatible sibling donor.
• For allogeneic transplant from fully matched siblings, long-term
survival rates for children are approximately 90%.

15.  IMMUNOSUPPRESSION
• Antithymocyte globulin (ATG) in combination with cyclosporine.
• It induces hematologic recovery in 60–70% of patients.
• Relapse is frequent.
• Horse ATG is administered as intravenous infusions over 4 days.
• Methylprednisolone is administered with ATG to ameliorate the immune
consequences of heterologous protein infusion.
• Cyclosporine is administered orally at an initial high dose, with subsequent
adjustment according to blood levels obtained every 2 weeks.

16. SUPPORTIVE CARE
• Infection in the presence of severe neutropenia must be aggressively
treated by prompt institution of parenteral, broad-spectrum antibiotics.
• Both platelet and erythrocyte numbers can be maintained by transfusion.
• RBCs should be transfused to maintain a normal level of activity, usually at
a hemoglobin value of 7 g/dL.
• A regimen of 2 units every 2 weeks will replace normal losses in a patient
without a functioning bone marrow.
• In chronic anemia, the iron chelators, deferoxamine and deferasirox, should
be added at approximately the fiftieth transfusion to avoid secondary
hemochromatosis.

17. PROGNOSIS
• The natural history of severe aplastic anemia is rapid deterioration and
death.
• The major prognostic determinant is the blood count.
• Severe disease has been defined by the presence of two of three
parameters:
- absolute neutrophil count <500/Μl
- platelet count <20,000/μL
- corrected reticulocyte count <1%.