Overview of Acquired Bone Marrow Failure Syndromes PDF

OVERVIEW OF ACQUIRED BONE MARROW FAILURE SYNDROMES Dr Efobi PANCYTOPENIA  Reduction in blood count of all cells- red cells, white cells, platelets.  Causes include:  Aplasia  Acute leukaemia, myelodysplasia, myeloma  Bone marrow infiltration by lymphoma, solid tumors and tuberculosis ...

OVERVIEW OF ACQUIRED BONE MARROW FAILURE SYNDROMES Dr Efobi PANCYTOPENIA  Reduction in blood count of all cells- red cells, white cells, platelets.  Causes include:  Aplasia  Acute leukaemia, myelodysplasia, myeloma  Bone marrow infiltration by lymphoma, solid tumors and tuberculosis  Megaloblastic anemia  Paroxysmal nocturnal hemoglobinuria  Myelofibrosis  Hemophagocytic syndrome  Splenomegally  Increased peripheral destruction eg Systemic lupus erythematosus BONE MARROW FAILURE  Similar to failure of an organ like the heart to perform its physiological function of blood circulation, bone marrow failure refers to inability of the marrow to produce a normal number of red blood cells, granulocytes and platelets due to intrinsic disease of the bone marrow itself.  This does not include pancytopenia caused by folate or iron deficiency or erythropoietin deficiency as seen in chronic renal failure.  Bone marrow failure causes can be inherited or acquired  Examples of conditions that will lead to acquired bone marrow failure include: aplastic anaemia, leukaemias, myelodysplasia. APLASTIC ANAEMIA  It is a classical example of bone marrow failure  It is defined as a condition in which there is pancytopenia resulting from bone marrow hypoplasia, without bone marrow infiltration by abnormal cells or fibrous tissue.  It is classified into  Primary  Congenital: fanconi’s anemia, dyskeratosis congenita  Acquired: aplastic anaemia  Secondary types ACQUIRED APLASTIC ANEMIA  More common than the congenital type  Incidence is 1-2/ million population per year and is 2-3x higher in south east Asia and Japan  It has a bimodal age distribution of 10-25yrs and >60years  No sex preponderance CAUSES OF ACQUIRED AA  Primary: idiopathic  Secondary:  Ionizing radiation accidental exposure to radiotherapy, radioactive isotopes  Chemicals like: Benzene, organophosphates, pesticides, recreational drugs  Drugs like busulphan, melphalan, cyclophosphamide, anthracyclines. Some drugs cause AA due to idiosyncrasy eg chloramphenicol, sulphonamides, gold (gold sodium thiomalate), anti-inflammatory, antithyroid drugs, etc Paroxysmal nocturnal hemoglobinuria Viruses: viral hepatitis- (Non- A, non- B, non- C, non-G), EBV Autoimmune diseases like SLE Transfusion associated graft versus host disease Thymoma Pregnancy PATHOGENESIS  Reduction in number of hemopoietic pluripotential stem cells and a fault in the remaining stem cells affecting capacity to self renew, proliferate and differentiate  Defective Hemopoietic microenvironment that is not able to sustain hemopoiesis  Deficiency of growth factors stimulating hemopoiesis  Immune mediated destruction of hemopoietic stem cells. Some individuals have clones of cytotoxic T lymphocytes that induce apoptosis of hemopoietic progenitor cells.  A number of patients have loss of function mutation in genes of telomerase complex CLINICAL FEATURES  Clinical features may be insidious or acute with symptoms of anemia, neutropenia or thrombocytopenia. Patient might present with:  Weakness, easy tiredness, palor of palms and mucous membrane due to anemia  Bruising, bleeding gums, epistaxis, menorrhagia, bleeding into the retina leading to visual impairment due to thrombocytopenia  Recurrent infections  Past history of jaundice, suggesting associated aetiological factor, hepatitis  Obtain a detailed drug history  Recurrent infections from neutropenia especially Throat and mouth infections. Infections can be generalized.  Lymphadenopathy, spleen and liver are not enlarged on examination. This helps rule out other causes of bone marrow failure such as lymphomas and leukaemias.  NB: a careful history and examination is very important, to rule out congenital aplastic anaemia.  A child or young adult  Short stature  Skeletal anomalies  Skin pigmentation( café-au- lait spots)  Small eyes, small head, small male genitalia,VSD, mental retardation, learning difficulty, GI malformations- Fanconi’s anaemia  Leukoplakia, nail dystrophy, skin pigmentation- dyskeratosis congenital. INVESTIGATION  Tests for making a diagnosis:  FBC: anaemia, neutropenia, thrombocytopenia, reticulocytopenia  Peripheral blood film: normocytic, normochromic red cells, reduction in all cell lines and no abnormal cells  Bone marrow aspiration: hypoplasia with replacement of hemopoietic cells with fat cells. Predominant cells are plasma cells and lymphocytes.  Trephine biopsy: patchy cellular areas in a hypo cellular background .  Tests to determine the cause of Aplastic anaemia.  LFT[liver function test]: elevated transaminases and bilirubin may suggest previous hepatitis  Autoantibody screening: may reveal underlying systemic disease like SLE  Abdominal USS: to detect hepatosplenomegaly and intra abdominal lymph nodes enlargement.  Cytogenetic and molecular analysis is performed to exclude inherited forms of aplastic anemia and hypocellular myelodysplasia  Anti nuclear antibody and anti-DNA antibody screening for SLE  Hams test and flow cytometry for CD55 and CD59 antigen for PNH  Viral screening  GRADING OF AA  Severe AA  Reticulocyte count