This document discusses various types of bone marrow failure syndromes including aplastic anemia, Fanconi anemia, pure red cell aplasia, myelophthisic anemia, and polycythemia. Aplastic anemia is a syndrome of chronic primary hematopoietic failure caused by a stem cell defect that results in pancytopenia. Fanconi anemia is an inherited disorder characterized by bone marrow hypoplasia and physical abnormalities. Pure red cell aplasia is a primary marrow disorder where only erythroid progenitors are suppressed. Myelophthisic anemia occurs when solid tumors destroy bone marrow architecture. Polycythemia is a myeloproliferative disorder resulting in increased red blood

1. Aplastic Anemia
Dr.CSBR.Prasad, M.D.,

2. Definition
• Aplastic anemia refers to a syndrome of
chronic primary hematopoietic failure and
attendant pancytopenia
– Anemia
– Neutropenia, and
– Thrombocytopenia

3. Mechanisms
Stem cell defect:
• Autoimmune (Most common)
• Inherited or
• Acquired

4. Major Causes of Aplastic Anemia

5. Aplastic Anemias
Fanconi anemia
• AR disorder
• Defect in DNA repair
• Marrow hypoplasia
• Hypoplasia of kidney, spleen
• Hypoplastic anomalies of bone – Thumb, Radius

6. Fanconi anemia

7. Aplastic Anemias - Pathogenesis
Environmental factors trigger the production of
genetically altered stem cells
1. Immunologically mediated suppression of
stem cells
By cytokines released by T cells
2. Intrinsic abnormality of stem cells
↓ proliferation & differentiating capacity

8. Pathophysiology of aplastic anemia

9. Aplastic Anemias - Morphology
• BM Aspiration – Dry tap
• BM biopsy – Diagnostic
• BM – markedly hypocellular
• Empty marrow spaces - fat, fibrous tissue,
lymphocytes, plasma cells

10. Aplastic anemia

11. Morphology

12. Aplastic Anemias
PBS
• NCNC, slight macrocytosis
• Reticulocytosis is absent
• Leukopenia
• Thrombocytopenia

13. Clinical Features
• Can occur at any age
• Onset is usually insidious
• Initial manifestations vary depending on the
affected cell line
• Splenomegaly is absent
• Reticulocytopenia is the rule
If it is present, the diagnosis of
aplastic anemia should be
seriously questioned

14. Aplastic Anemia
• DD
– MDS
– Aleukemic leukemia
Treatment
• Allogenic BMT
• Antithymocyte globulin along with
cyclosporine

15. Mary Curie

16. Pure Red Cell Aplasia

17. • It’s a primary marrow disorder in which only
erythroid progenitors are suppressed
• Causes:
– Thymoma
– Large granular lymphocytic leukemia
– Drug exposures
– Autoimmune disorders
– Parvovirus infection B19

18. Myelophthisic anemia

19. Myelophthisic anemia
SOL destroys BM architecture & depresses its
productive capacity
Causes
1. Metastatic cancer –
lung, breast, prostate, thyroid
2. Multiple myeloma, leukemia, lymphoma
3. Myelofibrosis
PBS - Leukoerythroblastosis

20. Polycythemia

21. Polycythemia
• Myeloproliferative disorder
– Unregulated proliferation of erythroid elements in
BM
– ↑ Erythrocyte concentration in peripheral blood
• Also ↑ other blood cells
• Synonyms: Polycythemia rubra vera, primary
polycythemia, erythemia

22. Polycythemia
• Polycythemia Vera – primary
• Secondary Polycythemia
– Appropriate to erythropoietin production
• High altitude
• COPD
• Obesity
– Inappropriate to erythropoietin production
• Tumors – RCC, HCC, uterine leiomyoma
• Renal ischemia
– Familial Polycythemia
• Relative Polycythemia
– Gaisbock’s syndrome
– Dehydration

23. Polycythemia Vera
• Unknown cause
• Possible mechanisms
– Erythropoietin independent proliferation of
neoplastic stem cells
– Hypersensitivity of erythroid stem cells to
erythropoietin
– Hypersensitivity of erythroid stem cells to insulin
growth factors
– Abnormal GF that act on normal stem cells

24. Polycythemia Vera – C/F
• 40- 60 years
• M>F
• Gradual in onset
• Headache, weakness, pruritis, weight loss,
fatigue
• GIT bleeding, menorrhagia, hemoptysis
• MI, Renal vein thrombosis, cerebral ischemia

25. Plethora of polycythemia

26. Polycythemia Vera – C/F
• Splenomegaly – 75%
• Hepatomegaly – 50%
• Hypertension – 50%
• Long standing cases – myelofibrosis – 30%
• 10% cases develop into acute leukemia

27. Polycythemia Vera – Lab findings
• Absolute Erythrocytosis: > 6-10millions/cumm
• Hemoglobin: > 18 gm%
• PCV > 48% in F, > 52% in M
• ESR – 2-3mm/ hour
• Reticulocyte count – normal / mildly increased
• Leukocytosis: > 12,000/mm3
• Platelet count - ↑
• PBS – NNBP, MCHC

28. Polycythemia Vera – Lab findings
• BM –
– hypercellular
– 95% cases - ↑ megakaryocytes
– ↑ reticulin
• Treatment
– Phlebotomy
– Myelosuppresive therapy

29. END

30. Dr.CSBR.Prasad, M.D.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.
csbrprasad@reiffmail.com