1b BONE MARROW FAILURE Year 4 Internal Medicine Notes

1b BONE MARROW FAILURE Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 BONE MARROW FAILURE DR ALEX MOGERE Consultant Physician Slide 2 OBJECTIVES Definition Classification Aetiology Pathology Clinical features Lab Investigation Treatment Slide 3 Definition Specific failure of bone marrow B cells to produce the normal number of mature cells resulting in peripheral blood cytopenias Bone marrow failure is also known as APLASTIC ANAEMIA Slide 4 CLASSIFICATION Primary- Idiopathic Secondary \n– Exposure to toxic agents eg drugs, chemicals, viruses Associated with-Fanconi’s anemia, infective hepatitis, pancreatic insufficiency, PNH, pure red cell aplasia (both congenital & acquired) Slide 5 AETIOLOGY 1- Inevitable – Ionizing radiation & cytotoxic drugs 2- Idiosyncratic – Idiopathic, drug induced, viruses (hepatitis, EBV, HIV, HPV, Dengue fever, Parvovirus ), some mycobacteria, commercial solvents 3- Inherited-Fanconi’s, Dyskeratosis congenita, diamond-blackfan anemia,others 4- Industrial- Benzene Slide 6 5- Immune- Drug induced, viruses (EBV), SLE 6- Infiltrations\n-infective- Leishmaniasis, miliary TB\n-storage disorders- Gaucher’s,\n-malignancies- lymphomas, plasma cell dyscrasias, metastatic carcinomas, myeloproliferative disorders both leukemic & non-leukemic Slide 7 DRUGS STONGLY LINKED TO APLASTIC ANAEMIA 1 – Antibiotics – chloramphenicol, sulphonamides including cotrimoxazole 2 – NSAIDS – phenyl butazone, gold salts, indomethacin, benoxaprofen, piroxicam 3 –Antithyroids – thiouracils, carbimazole 4 – Antimalarials – amodiaquine, pyrimethamine 5 – Anticonvulsants – phenytoin 6 – Antidepressants – chlorpromazine, prothiaden Slide 8 PATHOLOGY Postulated mechanisms; 1 – Qualitative Common Stem cell defect 2 - Defective bone marrow microenvironment 3 - Immune suppression Slide 9 DDX OF ACQUIRED BMF PNH MDS Large granular lymphocytic leukemia Immune pancytopenias in CTD eg Refractory anemia in SLE AML Hairy cell leukemia(B Lymphocytes) anemia Slide 10 CLINICAL FEATURES Primary much less common than Secondary Primary occurs in all ages but rare in infants & children. It maybe acute or chronic. Secondary occurs in all ages. It may be acute or chronic Slide 11 Features due to Cytopenia 1 – Anaemia – lassitude, fatiguability, dyspnoea 2 – Leukopenia – fever, chills, mouth ulcers, recurrent infections 3 – Thrombocytopenia – echymoses, petechiae, haemorrhage Slide 12 Features due to cause Chemical toxicity – rash, pruritus, arthralgia Drugs – signs &symtoms of the original condition for which the drug was used Marrow infiltrations - s & s of the infiltrative disease Features of the associated diseases Slide 13 LABORATORY FEATURES 1 – TBC – low Hb, low rbc,normal indeces\n-low wbc – total with neutropenia\n- low platelets 2 – PBF – normocytic normochromic with \nabsent polychromasia 3 – ESR – raised 4 – BMA – hypoplastic/aplastic or a dry tap or \nmarrow infiltrations 5 - Trephine – reduced haemopoeitic tissue with \nincreased fat spaces & stroma 6 – Others – due to asociated conditions, infiltrative conditions,diseases Slide 14 TREATMENT 1 – SUPPORTIVE\nAnaemia – packed rbc if in failure\nInfections – relevant antibiotics\nHaemorrhage – platelet concentrates\nSplenectomy – is indicated if;\n-transfusion dependent or\n-not responding to therapy Slide 15 2 – DEFINITIVE TREATMENT 1 – BMT – young & HLA matched 2 – Immunosuppression – ALG\n-highdose steroid\n-cytotoxics 3 – Androgens – oxymetholone & steroids 4 – Others – growth factors 5 – Treatment of cause or original disease Slide 16 Ct Tx ATG OR ALG should be given with corticosteroids to prevent serum sickness High dose methylprednisolone (20mg/kg/day with rapid taper), if ATG /ALG is expensive Cyclosporine therapy at a dose of 200-400mg/d has a reported 85% hematologic remission rate Androgens are poorly tolerated by females and children(but include testosterone proprionate, nandrolone decanoate, oxymetholone etc) Danazol is a non masculinizing androgen that may be useful Hematopoietic growth factors eg G-csf,GM-csf in neutropenic cases Slide 17 THANK YOU!