(All the articles published in past are available at www.shyamhemoncclinic.com)
Question: Dr. Chiragbhai, thank you for explaining in last part about diagnosis and treatment of eosinophilia including role of new medicines like imatinib, mepolizumab and other important aspects.
Ans: Now we are going to discuss a very important non malignant but serious blood disorder, frequently even more serious than many cancers, known as “APLASTIC ANEMIA”. Most doctors are familiar with this general term, but may not be aware of some important aspects, especially importance of early treatment and less number of transfusions for better outcome, and the risk of serious infections and early death in severe aplastic anemia.
Que: You are right. I have seen young patients dying in first one or two months after diagnosis, while they were still deciding about treatment. But what are the causes? How to prevent?
Ans: It is thought be related to autoimmune damage to bone marrow stem cells. In less than 10% cases, following causes can be found. They are important to know as some of these cases, such as drug induced, require withdrawal of offending drug.
1. Medicines: Old NSAIDs like phynylbutazone or indomethacin; anticonvulsants like carbamazepine, valproic acid, phenytoin; antithyroids like methimazole, propylthiouracil; antibiotics like sulfonamides, chloramphenicol; gold, arsenic (both sometimes used in ayurvedic medicines); chemotherapy in high doses.
2. Radiation in high doses
3. Chemicals: benzene (used in rubber factories etc), some pesticides fertilizers, solvents etc
4. Infections: EBV; viral hepatitis (non A, B, C ) – generally 2-3 months after hepatitis; parvovirus especially in immunocompromised patients; HIV; herpes viruses.
5. Immune diseases: SLE, GVHD, Eosinopilic fasciitis
6. Others: PNH, thymoma, anorexia nervosa, pregnancy
Once again, remember that over 90% patients have no obvious underlying cause.
Que: So, this is autoimmune destruction of stem cells, something like ITP?
Ans: Yes, but in ITP, antibodies destroy megakaryocytes. In aplastic anemia, lymphocytes destroy stem cells. There are no tests in clinical use for this mechanism however.
Patients present with pancytopenia and related symptoms such as fatigue, fever, sepsis or bleeding. There are no specific symptoms or signs. In fact, presence of lymphadenopathy or hepato or splenomegaly must alert one to look for other diagnoses.
Work up shows a hypocellular bone marrow. It is important to note that bone marrow aspirate is not sufficient for this diagnosis. A good trephine biopsy is MANDATORY to establish diagnosis.
Important differential diagnoses include 1. hypocellular myelodysplastic syndrome (ruled out by morphology of marrow cells and normal cytogenetics), 2. tumor infiltration or some infections causing marrow fibrosis (ruled out by marrow appearance), 3. viral hemophagocytic syndrome (careful examination of marrow will show macrophages with hemophagocytosis; very high ferritin etc), 4. Fanconi anemia related aplastic anemia (important to rule out in children, even if there are no classical congenital anomalies like bifid thumb), 5. PNH-paroxysmal nocturnal hemoglobinuria (suspected if high LDH or other signs of hemolysis).
A small PNH clone is frequently present in patients with aplastic anemia. There is no change in management for such patients nor in prognosis or treatment results. Hence it is not recommended to routinely test for PNH in all patients with aplastic anemia.
Grading of aplastic anemia is clinically useful in determining prognosis and urgency of starting treatment. Severe (with absolute neutrophil count of <500 or platelet <20,000) or very severe (ANC<200) need urgent treatment. Also, blood should be collected for HLA typing before starting any transfusions, especially in patients younger than 40 years, for potential treatment with transplant later.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com