Topics Covered in This Page
Approach to Pancytopenia: 2 Bottom Line Points Etiology: Primary BM disease vs Systemic Disease Narrowing DDx: Based on BM biopsy findings along with other clinical features
Etiology - Due to Primary Bone Marrow Disease
- Myelophthistic Anemia: Myelofibrosis, myeloid metaplasia, ineffective erythropoiesis
- MDS, PNH, BM Lymbhoma, Aleukemic Leukemia etc
- Due to Systemic Disease: Infection (TB, Leishmaniasis, Brucellosis); Metobolic (B12, Folic Acid, Alcohol); Immune Mediated (SLE, Sarcoidosis); Hypersplenism
Narrowing DDx - Due to Hypocelluar BM (5 Groups):
- Congential Aplastic Anemia
- Fanconi Anemia
- Dyskeratosis Congenita
- Shwachman-Diamond Syndrome
- Amegakaryocytic thrombocytopenia
- Reticular Dysgenesis
- Acquired Aplastic Anemia
- Chemicals/Drugs
| Benzene | | Solvents | | Glue vapors |
| Anticonvulsants: carbamazepine, hydantoins, phenacemide | | Antibiotics: sulfonamides, chloramphenicol | | Non steroidal anti-inflammatory drugs (NSAIDs): phenylbutazone, indomethacin | | Anti-thyroid medications: methimazole, propylthiouracil | | Gold | Arsenicals
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- Cytotoxic Drugs or Radiation
- Viral Infections (EBV, HIV, Seronegative Hepatitis )
- Immune Disorders
| Eosinophilic fasciitis | | Systemic lupus erythematosus (can also cause hyper cellular marrow) | | Graft versus host disease |
- Idiopathic
| Thymoma | | Pregnancy | | Anorexia nervosa |
- PNH
- Hypoplastic MDS
- Large Granular Lyphocytic Lymphoma
- Despite Cellular BM: Primary BM Disease vs. Secondary to Systemic Disease (Table 107-1)
| Primary BM Disease | Secondary to systemic ds | | MDS | Hypersplenism | | PNH | B12 / Folate deficiency | | Myelofirbosis | SLE | | Myelopthisis | Overwhelming Infection | | BM Lymphoma | Alcohol | | Aleukemic Leukemia | Brucellosis | | Hairy Cell Leukemia | Sarcoidosis | | | Tuberculosis | | | Lishmaniasis |
- References
- Table 107–1 Differential Diagnosis of Pancytopenia Harrison's Textbook of Internal Medicine
Clinical Questions
23 y/o M is seen for petechial lesions. No Fever, or Chills. These are non-palpable petehice. Hgb is 7.2, WBC 1.2 (N: 34 %, L 63 %), ANC 400, Platelet 18000. What is the next step to do . USG abdomen is done. Liver and Spleen are of normal size.
HIV, B12, Folate. All were normal or non-reactive.
Next step is. BM biopsy. Findings include.
Erythroid: 21 % Meta / myelocyte: 5 % Lymphocytes: 41 % Neutrophil: 29 % Monocyte: 2 % Plasma Cell 1 % Blasts: 0 % Eosinophils: 1 %
Overall Markedly Hypocellular Iron stain: Markedly reduced Myeloid: Normal Morphology seen Megakaryocytes: Not seen
What is the diagnosis: Aplastic Anemia: Aplastic anemia is typically a disease of a young.
How severe is the aplastic anemia. Severe: ANC 200-500, Platelet < 20000, Absoulte reticulocyte count < 40,000. Very severe: ANC < 200
With a Hypocellular Bone Marrow, What is the DDx.
| Congential Disorders | | Acquired Disorders | - Often present with abrupt onset of low blood counts in a healthy individual
- Seronegative hepatitis or medical drug use often precede this
| | Fanconi Anemia | - DNA repair defect
- Can present as a marrow failure in a normal-appearing adults
| Chemical Drugs | No use of chemical drugs, but need to ask about NSAIDS | | Dyskeratosis Congenita | - Can present as a marrow failure in a normal-appearing adults
| Cytotoxic Drugs or Radiation | No such use of cytotoxic drugs or radiation |
Shwachman-Diamond Syndrome | | Viral / other Infections
- HIV
- EBV (IM)
- Seronegative Hepatitis
- Miliary TB
| - HIV is negative
- Hepatitis in the previous 1-2 months is seen in 5 % of such case series
- Rarely follows Infectious Mononucleosis
- Tests for EBV or seronegative Hepatitis should be done
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Amegakaryocytic thrombocytopenia | - Typically presents early in the age
- Acquired form may present later
- Typically, present with only thrombocytopenia
| Immune Disorders
- SLE
- Eiosinophilic Fascitis
- GVHD
| - None were present in this patient
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Reticular Dysgenesis | - Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate.
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558504/
| Idiopathic Causes (Thymoma, Pregnancy, Anorexia Nervosa) | - Needs to be assessed for Thymoma
| | | | Other Acquired Causes:
- PNH
- Hypoplastic MDS
- Large Granular Lympocytic Lymphoma
| - PNH in younger individual may later develop frank aplastic anemia years later. Similraly, patient with aplastic anemia upfront may develop hemolytic anemia years later. So, either of the presentation can occur. Hence, PNH is still a possibility.
- Hypoplastic MDS is favored by morphologically abnormalities. This is especially in Megakaryocytes, and Myeloid precursor cells, and cytogentic testings.
- No Lymphoma were seen
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Next step: - Diepoxybutaine or Mitomycin C induced chromosomal breakdown test in peripheral blood to test for Fanconi Anemia. Very short telomere telomerase is often seen.
- Chromosome studies of BM cells are often reveling in MDS
- Flow cytometry offers a sensitive diagnostic tests for PNH
- Serological Studies for EBV, and HIV should be done if not done
- Review the concern for Miliary TB
What determines the prognosis
Cell counts
Absoulte retic count > 25K/uL, and Lymphocytes >1K/uL confers better prognosis in the era of effective immunosupressive therapies
References: - Pancytopenia Harrison's Textbook of Internal Medicine
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