1. Myeloproliferative Disorder
STEM CELL DISORDERS WHEREBY YOU GET ABNORMAL PROLIFERATION IN ONE OR MORE CELL LINE DERIVED FROM A COMMON STEM CELL

2. THE INDIVIDUAL FEATURE OF THESE DISEASES RESULT FROM A:
DISTURBED HAEMOPOIETIC MICROENVIRONMENT
CLONAL ABNORMALITY
DISTURBANCE IN HAEMOPOIETIC REGULATION.

3. Myeloproliferative Disorder
Polycythaemia Ruba Vera
Myelofibrosis
Primary Thrombocytopenia
Chronic Myeloid Leukaemia
Myeloproliferative Disorder – unclassifiable
Chronic Eosinophilic Leukaemia

4. 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

5. CMPD Disease of Adults Peak Onset 50-70 6-9/100,000
Limited Geographical Based Data

6. PRIMARY THROMBOCYTHAEMIA
PLATELETS > 600 X 109/L
^ MEGAKARYOCYTES IN THE MARROW
CLONAL DISORDER OF THE MULTIPOTENTIAL STEM CELL

7. Primary Thrombocythaemi - Pathogenesis
Aetiology – Unknown
Megakaryocytic hyperplasia
Functionally abnormal platelets

8. Primary Thrombocythaemia Clinical Features
Asymptomatic
Vasomotor- 40%
Haemorrhage – 25%
Thrombosis – 20%
Splenomegaly
Recurrent Miscarriage

9. 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

10. PRIMARY THOMBOCYTOSIS
DIAGNOSIS:
EXCLUDE CAUSE OF REACTIVE THROMBOCYTOSIS.
EG: ACUTE HAEMORRHAGE
MALIGNANT DISEASE,
CHRONIC INFLAMM
DISORDER,
ACUTE INFLAM
POST-OP SPLENECTOMY
EXERCISE
IRON DEF.

11. PRIMARY THROMBOCYTHAEMIA
TREATMENT
MYELOSUPPRESIVE HYROXUREA ANAGRELIDE
ANTI-PLATELET AGENTS
INTERFERON

12. POLYCYTHAEMIA
Absolute polycythaemia
Relative polycythaemia

13. 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.

14. CLINICAL FEATURES OF P.R.V
Older Age , 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 %
Skin Change - Pletharic Facies, Acne Roscea,

15. CLINICAL FEATURES OF P.R.V. CONTD.
^ URIC ACID - GOUT
^ BP
SPLENOMEGALY - 50%
LAB * ^HB ^PCV - MALE - HB 17.5G/L, PCV > 0.51
- FEMALE HB15.5G/L, PCV > 0.46
^ WCC
^PLATELETS 50% X 109/L
^ B12
LEUCOCYTE ALKALINE PHOSPHATASE.
MARROW - HYPERCELLUAR

16. DIAGNOSTIC CRITERIA OF PPP OR PRV
^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/^B12
COURSE: % - MYELOFIBROSIS
2-10% - ACUTE LEUKAEMIA
RX VENESECTION REGULARILY
CHEMOTHERAPY , HYDROXYREA
ANTIPLATELET THERAPY

17. 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.

18. MANAGEMENT OF P.R.V PREVENTION OF VASCULAR OCCLUSIONS
DELAY MYELOFIBROTIC TRANSFORMATION
MINIMIZE ACUTE LEUKAEMIC TRANSFORMATION.
PHLEBOTOMY
MYELOSUPPRESSIVE
ANTIPLATELET AGENT.

19. P.R.V. COURSE: 15-20% - MYELOFIBROSIS 2-10% - ACUTE LUEKAEMIA RX:
VENESECTION REGULARLY
CHEMOTHERAPY 35p HYDROXYURIA
ANTIPLATELET THERAPY

20. MYELOFIBROSIS (agnogenic myeloid metaplasia)
1o DISORDER
- OR - AS PART OF OTHER MYELOPROLIFERATIVE DISORDERS
20% HAVE HX OF PRV
2ND LYMPHOPROLIFERATIVE, BENZENE, FLUORINE, ANSENIC

21. MYELOFIBROSIS (agnogenic myeloid metaplasia)
PATHOLOGY:
^ Connective tissue within the bone marrow.
^ Collagen
^ New bone formation
destruction of normal marrow microenvironment
^ circ stem cells: cells normally present in the marrow
Dysplastic Feature.
Extramedullary haemopoiesis - eg. liver.

22. 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

23. Myeloproliferative Disorders Chronic Granulocytic Leukaemia
First malignancy associated with a recurring chromosomal abnormality
Translocation of genetic material from chromosomes 9 22
Fusion gene fusion protein - pathogenesis

24. CHRONIC GRANULOCYTIC LEUKAEMIA = CHRONIC MYELOID LEUKAEMIA
1/100,000
MALE > FEMALE
5TH - 6TH DECIDE BUT CAN OCCUR AT ANY AGE
PH CHROMOCOSME - RECIPROCAL TRANSLOCATION BETWEEN CHROMOSOME
9 => 22 = ? AETIOLOGICAL SIGNIFICANCE OR ? MARKER DISEASE.
=> CLONAL DISORDER OF HAEMOPOIETIC STEM CELL
? PROCESS - GROWTH ADVANTAGE
=> X 30 FIELD ^ IN GRANULOCTE MASS

25. C.G.L. CLINICAL FEATURES: BIPHASIC OR TIRPHASIC DISEASE
CRONIC ACCELERATED
TRANSFORMATION
20% ASYMPTOMATIC
NON-SPECIFIC COMPLAINTS
SPLENAMEGALY AND HEPATOMEGALY

26. C.G.L. LAB FEATURES: LEUCOCYTOSIS - 100 -300 x 109/L. BASOPHILIA
THROMBOCYTOSIS
HYPERCELLULAR MARROW
PH POSITIVE IN 90%
INCREASED MARROW FIBROSIS.

27. C.G.L. TREATMENT OF C.G.L: BONE MARROW TRANSPLANT
CYTOREDUCTIVE THERAPY
TYROSINE KINASE INHIBITORS
E.G. HYDROXYUREA,
INTERFERON
MANAGEMENT OF METABOLIC COMPLICATIONS.