1 stem cell disorders whereby you get abnormal proliferation in one or more cell line derived from a...
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STEM CELL DISORDERS WHEREBY YOU GET ABNORMAL
PROLIFERATION IN ONE OR MORE CELL LINE DERIVED FROM A
COMMON STEM CELL
Myeloproliferative Disorder
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THE INDIVIDUAL FEATURE OF THESE DISEASES RESULT FROM A:
•DISTURBED HAEMOPOIETIC MICROENVIRONMENT
•CLONAL ABNORMALITY
•DISTURBANCE IN HAEMOPOIETIC REGULATION.
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Myeloproliferative Disorder
• Polycythaemia Ruba Vera
• Myelofibrosis
• Primary Thrombocytopenia
• Chronic Myeloid Leukaemia
• Myeloproliferative Disorder – unclassifiable
• Chronic Eosinophilic Leukaemia
• Chronic Myeloid Leukaemia
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CMPD- COMMON FEATURES
• Proliferation and differention of one or more stem cell.
• Raised W.C.C.. HB, Platelets
• Organomegaly
• Extramedullary Haematopoiesis
• Clinical, Laboratory and Morphological overlap
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CMPD
• Disease of Adults
• Peak Onset 50-70
• 6-9/100,000
• Limited Geographical Based Data
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PLATELETS > 600 X 109/L
^ MEGAKARYOCYTES IN THE MARROW
CLONAL DISORDER OF THE MULTIPOTENTIAL STEM CELL
PRIMARY THROMBOCYTHAEMIAPRIMARY THROMBOCYTHAEMIA
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Primary Thrombocythaemi - Pathogenesis
Aetiology – Unknown
Megakaryocytic hyperplasia
Functionally abnormal platelets
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Primary ThrombocythaemiaClinical Features
• Asymptomatic
• Vasomotor- 40%
• Haemorrhage – 25%
• Thrombosis – 20%
• Splenomegaly
• Recurrent Miscarriage
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PRIMARY THROMBOCYTOSIS
DIAGNOSTIC CRITERIA
PLATELET COUNT > 600X109/L FOR OVER 2 MONTH WITH NO CAUSE OF REACTIVE THOMBOCYTOSIS, NO EVIDENCE OF PRV, MYELOFIBROSIS, MYELODYSPLASIA AND NO PH CHROMASOME
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PRIMARY THOMBOCYTOSIS
DIAGNOSIS:EXCLUDE CAUSE OF REACTIVE THROMBOCYTOSIS.EG: ACUTE HAEMORRHAGEMALIGNANT DISEASE,CHRONIC INFLAMMDISORDER, ACUTE INFLAMPOST-OP SPLENECTOMYEXERCISE IRON DEF.
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PRIMARY THROMBOCYTHAEMIA
TREATMENT
MYELOSUPPRESIVE HYROXUREA ANAGRELIDE
ANTI-PLATELET AGENTS
INTERFERON
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POLYCYTHAEMIA
• Absolute polycythaemia
• Relative polycythaemia
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ABSOLUTE POLYCYTHAEMIA
. PRIMARY POLYCYTHAEMIA - POLYCYTHAEMIA RUBRA VERA
- ERYTHROPOIETIC RECEPTOR GENE MUTATION. 2. SECONDARY POLYCYTHAEMIA
- HYPOXAEMIA POO
< 92%
- RENAL DISEASE - TISSUE HYPOXIA - HIGH AFFINITY HB
- TUMOURS - HEPATOMAS, FIBROIDS, CEREBELLAR- HAEMANGIOBLASTOMAS- HIGH ERYTHROPOIET PRODUCTION
3 IDIOPATHIC ERYTHROCYTOSIS.
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• Older Age - 50 - 60, Female > Male• Vascular Complications - Arterial = Venous• Cerebral + Coronary - Headache - Dizziness• Due to Small Vessel Occlusion.• => 30-50% - Thrombotic - Art = Venus, Sml & Lrg
Vessels• - Haemorrhagic• Peptic Ulceration - ^ Histamine Levels• Prutritis - 20-25%• Skin Change - Pletharic Facies, Acne Roscea,
CLINICAL FEATURES OF P.R.V
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CLINICAL FEATURES OF P.R.V. CONTD.
^ URIC ACID - GOUT^ BPSPLENOMEGALY - 50%LAB * ^HB ^PCV - MALE - HB 17.5G/L, PCV > 0.51 - FEMALE HB15.5G/L, PCV > 0.46^ WCC^PLATELETS 50% - 400 - 800X 109/L^ B12 LEUCOCYTE ALKALINE PHOSPHATASE.MARROW - HYPERCELLUAR
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^RCM > 36ML/KG IN MALES - 32ML/KG IN FEMALES NO EVIDENCE OF A CAUSE OF SECONDARY POLYCYTHAEMIA INCLUDING ARTERIAL OXYGEN SATURATION > 92%
+ SPLENOMEGALY (PALPABLE)IF (-) SPLENOMEGALY PALPABLE - PLATELET > 400 - ^WCC > 12 - ^ LAP/^B12COURSE: 15-20% - MYELOFIBROSIS 2-10% - ACUTE LEUKAEMIARX VENESECTION REGULARILY CHEMOTHERAPY , HYDROXYREA ANTIPLATELET THERAPY
DIAGNOSTIC CRITERIA OFPPP OR PRV
DIAGNOSTIC CRITERIA OFPPP OR PRV
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Investigation of Polycythaemia
• RED CELL MASS STUDIES AIM IS TO INVESTIGATE/EXCLUDE A CAUSE OF SECONDARY POLYCYTHAEMIA
• CLINICAL EVALUATION• PULSE OXIMETRY • RENAL - URINALYSIS + RENAL ULTRASOUND• ABDOMINAL ULTRASOUND• NEUTROPHIL COUNT• PLATELET COUNT• MARROW CYTOGENETICS• MARROW CULTURE• SERUM ERYTHROPOIETIN ASSAYS.
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• PREVENTION OF VASCULAR OCCLUSIONS• DELAY MYELOFIBROTIC
TRANSFORMATION• MINIMIZE ACUTE LEUKAEMIC
TRANSFORMATION.• PHLEBOTOMY• MYELOSUPPRESSIVE• ANTIPLATELET AGENT.
MANAGEMENT OF P.R.VMANAGEMENT OF P.R.V
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P.R.V.
COURSE:
15-20% - MYELOFIBROSIS
2-10% - ACUTE LUEKAEMIA
RX:
VENESECTION REGULARLY
CHEMOTHERAPY 35p HYDROXYURIA
ANTIPLATELET THERAPY
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MYELOFIBROSIS(agnogenic myeloid metaplasia)1o DISORDER
- OR - AS PART OF OTHER MYELOPROLIFERATIVE DISORDERS
20% HAVE HX OF PRV
2ND LYMPHOPROLIFERATIVE, BENZENE, FLUORINE, ANSENIC
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MYELOFIBROSIS(agnogenic myeloid metaplasia)PATHOLOGY:^ Connective tissue within the bone marrow.^ Collagen^ New bone formationdestruction of normal marrow microenvironment^ circ stem cells: cells normally present in the
marrow Dysplastic Feature.Extramedullary haemopoiesis - eg. liver.
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MYELOFIBROSIS(agnogenic myeloid metaplasia)SYMPTOMS:
OFTEN ASYMPTOMATIC:
BONE MARROW FAILURE
^ SPLEEN - LUQ PAIN
METABOLIC CONSEQUENCE OF M/P DISORDER - SWEATS ^URIC ACID GOUT, RENAL COLIC
BLEEDING DIATHESIS
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Myeloproliferative DisordersChronic Granulocytic Leukaemia• First malignancy associated with a recurring
chromosomal abnormality
• Translocation of genetic material from chromosomes 9 22
• Fusion gene fusion protein - pathogenesis
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CHRONIC GRANULOCYTIC LEUKAEMIA = CHRONIC MYELOID LEUKAEMIA
1/100,000 MALE > FEMALE5TH - 6TH DECIDE BUT CAN OCCUR AT ANY AGEPH CHROMOCOSME - RECIPROCAL
TRANSLOCATION BETWEEN CHROMOSOME9 => 22 = ? AETIOLOGICAL SIGNIFICANCE OR ?
MARKER DISEASE.=> CLONAL DISORDER OF HAEMOPOIETIC STEM
CELL ? PROCESS - GROWTH ADVANTAGE=> X 30 FIELD ^ IN GRANULOCTE MASS
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CLINICAL FEATURES:
BIPHASIC OR TIRPHASIC DISEASE
CRONIC ACCELERATED
TRANSFORMATION
20% ASYMPTOMATIC
NON-SPECIFIC COMPLAINTS
SPLENAMEGALY AND HEPATOMEGALY
C.G.L.
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C.G.L.
LAB FEATURES:
LEUCOCYTOSIS - 100 -300 x 109/L.
BASOPHILIA
THROMBOCYTOSIS
HYPERCELLULAR MARROW
PH POSITIVE IN 90%
INCREASED MARROW FIBROSIS.
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C.G.L.
TREATMENT OF C.G.L:BONE MARROW TRANSPLANTCYTOREDUCTIVE THERAPY TYROSINE KINASE INHIBITORSE.G. HYDROXYUREA, INTERFERONMANAGEMENT OF METABOLIC
COMPLICATIONS.