1. MLAB 1415-Hematology Keri Brophy-Martinez
Hypoproliferative Anemias

2. Overview Disorders Anemia Defect Acquired Congenital
Normocytic or Macrocytic
Normochromic
Bone marrow hypocellularity
Defect
Depletion, damage or inhibition of stem and/or progenitor cells

3. APLASTIC ANEMIA Aplastic anemia
Disorder (or group of disorders) characterized by aplasia of bone marrow or its destruction by chemical agents or physical factors. All cell lines are affected.
Aplasia
Failure of a tissue or organ to develop normally

4. Pathophysiology
Aplastic anemia is caused by an immune process, either antibodies directed against the stem cell or a cellular immune mechanism (T-lymphocyte) that suppresses stem cell prolieferation
Bone marrow fails due to the immunologically mediated tissue-specific destruction

5. Phases
I: Onset
After an initiating event (i.e. viral infection) the hematopoietic cells are destroyed by the immune system
Small numbers of surviving stem cells can support adequate hematopoiesis for some time, but eventually the circulating cell counts become very low and clinical symptoms appear

6. Phases II: Recovery III: Late Disease
Either a partial response or a complete response can occur, initially, without increased number of stem cells
III: Late Disease
Years after recovery, blood counts may fall as pancytopenia occurs or as abnormal clones of stem cells emerge.
Often leads to PNH( paroxysmal noctural hemoglobinuria), AML (acute myelogenous leukemia) or MDS (myelodysplasia)

7. Aplastic Anemia Two Groups Acquired Congenital Majority of cases
Surface after age 60
Congenital
2-5 years old
15-25 years old

8. APLASTIC ANEMIA Acquired Idiopathic or primary with no clear cause
Secondary due to
Chemical agents such as benzene, insecticides, weed killers
Drugs such as chloramphenicol (antibiotic) and phenylbutazone (anti-inflammatory), chemotherapy drugs (busulfan, vincristine), anticonvulsants (Dilantin)
Ionizing radiation from nuclear fallout, x-rays or radiation therapy, radium
Infections such as hepatitis, Epstein-Barr virus, CMV, HIV
Miscellaneous - pregnancy, malnutrition, immunologic dysfunction

9. APLASTIC ANEMIA Congenital/ Inherited Aplastic Anemia Fanconi’s anemia
Genetic predisposition to bone marrow failure
Chromosomal breaks, gaps, exchanges
25- 30% cases of childhood aplastic anemia
Twice as common in males than females

10. Clinical Features Low birth weight Skin hyperpigmentation Short statue
Dyspnea
Bleeding
Infections
Skeletal disorders

11. Aplastic anemia : Lab Features
Total Bone marrow failure
Hypocellular: 70% fat
Pancytopenia= all cell lines affected

12. Aplastic Anemia: Lab Features
↓ RBC, hgb (<7), hct (<20), retic (absolute and corrected)
↓ WBC (<1.5) , absolute neutrophil count (<0.5)
Relative lymphocytosis due to the neutropenia
↓ platelets (<20,000-60,000)
P.B
Normocytic/macrocytic,normochromic
Moderate anisocytosis, poikilocytosis
NRBCs, teardrops*

13. Treatment
Treatment of choice is bone marrow transplantation. If this is not an option, immunotherapy is given. Spontaneous recovery may occur if the offending agent is removed.
Prognosis is poor, high mortality rate..2 years
Complications include
Bleeding
Iron overload due to transfusions

14. Pure red cell aplasia Rare condition
Red cell precursors in the bone marrow are decreased
Presence of peripheral blood anemia

15. Pure Red Cell Aplasia Congenital Acquired Diamond-Blackfan anemia
Defect in erythroid precursors
Acquired
Hemolytic crises
Infection with parvovirus, EBV, viral hepatitis
Malnutrition
Certain drugs or neoplasms

16. Other Hypoproliferative Anemias
Defective hormonal stimulation of erythroid progenitor cells
Kidney Disease
Endocrine Disorders
Lab findings reflect anemia and pathologies of primary disorder

17. References
Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: F.A Davis.
McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology . Upper Saddle River: Pearson Education, Inc.