maj gen (r) masood anwar. bone marrow failure syndromes can be defined as a group of diseases in...
TRANSCRIPT
![Page 1: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/1.jpg)
BONE MARROW FAILURE SYNDROMES
Maj Gen (R) Masood Anwar
![Page 2: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/2.jpg)
BONE MARROW FAILURE SYNDROMES
Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce mature and functional blood cells in required quantities. In peripheral blood it will manifest as pancytopenia, bicytopenia or some times monocytopenia.
![Page 3: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/3.jpg)
Suppression of normal bone marrow maturation (ineffective haemopoiesis)
Destruction or suppression of stem cells and/or microenvironment
Replacement of normal bone marrow with abnormal tissue or cells
Destruction of bone marrow with disease
CAUSES
![Page 4: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/4.jpg)
Most common cause is ineffective haemopoiesis because of Vitamin B12 and/or Folate deficiency – 29%
Aplastic anaemia – 22-27% All other causes for remaining <50%
CAUSES IN PAKISTAN
![Page 5: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/5.jpg)
Aplastic Anaemia is defined as pancytopenia in the peripheral blood with hypoplastic bone marrow and no evidence of any primary disease infiltrating, replacing or suppressing active haematopoiesis.
DEFINITION
![Page 6: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/6.jpg)
APLASTIC ANAEMIA
![Page 7: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/7.jpg)
Abnormalities of Stem cell Abnormalities of Stroma Abnormalities of cytokines
PATHOPHYSIOLOGY
![Page 8: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/8.jpg)
◦ Failure of stem cells to grow in normal culture
◦ Failure of normal stem cells to grow in patient
stromal cell culture
◦ High CSF releaser levels
◦ Decreased response of stem cells to CSF and EPO
PATHOGENESISExperimental findings
![Page 9: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/9.jpg)
EXTRINSIC AGENT
INTRINSIC DEFECT
SILENT IMMUNE MILD TO MODERATE
AUTOREACTIVITY
ACUTE DESTRUCTION
PATHOGENESIS
![Page 10: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/10.jpg)
Direct Injury (Secondary or Acquired)◦ Drugs (Iatrogenic), radiation, viruses◦ Drug toxicity is through intermediate
metabolites◦ Bind covalently to marrow cell proteins and
DNA leading to DNA damage and apoptosis◦ Radiation causes direct damage to DNA◦ Viruses intercalate with DNA
PATHOPHYSIOLOGY
![Page 11: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/11.jpg)
Immune Mediated (idiopathic)◦ Improvement in pancytopenia after failed
allogeneic BMT Immunosuppressive conditioning (ALG or
Cyclophosphamide) intended to allow engraftment of donor marrow might have promoted the function of host marrow*
BMT of an identical twin also requires immunosuppression
PATHOPHYSIOLOGY
![Page 12: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/12.jpg)
Immune Mediated (idiopathic)◦ Improvement in pancytopenia after failed
allogeneic BMT Immunosuppressive conditioning (ALG or
Cyclophosphamide) intended to allow engraftment of donor marrow might have promoted the function of host marrow*
BMT of an identical twin also requires immunosuppression
PATHOPHYSIOLOGY
![Page 13: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/13.jpg)
Immune Mediated (idiopathic)◦ Trials of IST (Immunosuppressive Therapy)◦ Most successful regimens have been multi-drug
combinations◦ Effectiveness of such trials strongly suggest
immune mediated cause of the disease
PATHOPHYSIOLOGY
![Page 14: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/14.jpg)
![Page 15: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/15.jpg)
Congenital Acquired
AETIOLOGY
![Page 16: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/16.jpg)
Skeletal◦ Short stature◦ Microcephaly◦ Radial anamolies◦ Hip and spine anamolies
Skin◦ Hyperpigmentation◦ Hypopigmentation
Genitiurinary tract◦ Renal tract anamolies◦ Hypogonadism
Craniofacial Gastrointestinal Cardiac No associated abnormalities
FANCONI ANEMIA
![Page 17: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/17.jpg)
FANCONI ANAEMIA
SHORTSTATURE
![Page 18: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/18.jpg)
FANCONI ANAEMIA
RADIAL ABNORMALITIES
![Page 19: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/19.jpg)
FANCONI ANAEMIA
RENALANAMOLIES
![Page 20: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/20.jpg)
CHROMOSOMAL FRAGMENTATION
![Page 21: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/21.jpg)
Primary Idiopathic Secondry
◦ PNH◦ Radiation◦ Chemicals◦ Viruses◦ Drugs
Regularly causing – cytotoxic Probably causing – chloramphenicol Rarely causing – Quinine etc
◦ Stroma and growth factors
ACQUIRED APLASTIC ANAEMIA
![Page 22: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/22.jpg)
Low Hb/Hct, TLC and platelet count defined for the age and sex together with hypocellular marrow
Conveniently divided into three groups for therapeutic decisions Non Severe Aplastic Anaemia
(NSAA) Severe Aplastic Anaemia (SAA) Very Severe Aplastic Anaemia
(VSAA)
DIAGNOSTIC CRITERIA
![Page 23: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/23.jpg)
Presenting complaints – anaemia, infection, bleeding
History – family, personal, occupational, drugs Physical examination – liver, spleen, lymph nodes Blood counts
◦ Hb <10 g/dl◦ Neutrophil count <1.0 X 10^9/l◦ Platelet count <100 X 10^9/l◦ Reticulocyte count (corrected) <1%◦ MCV ~100 fl
Bone marrow◦ Aspirate◦ Biopsy
DIAGNOSIS
![Page 24: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/24.jpg)
BONE MARROW ASPIRATE
![Page 25: Maj Gen (R) Masood Anwar. Bone marrow failure syndromes can be defined as a group of diseases in which occurs failure on the part of bone marrow to produce](https://reader035.vdocument.in/reader035/viewer/2022081512/56649ccc5503460f94995a02/html5/thumbnails/25.jpg)
BONE MARROW TREPHINE BIOPSY