Myeloproliferative disorders

Myeloproliferative disorders
They describe the inter-relationship exist between acute and chronic myeloid leukemias. They include:
1. Polycythemia rubra vera (primary polycythemia).
2. Essential thrombocythemia (primary thrombocytosis).
3. Myelofibrosis.

In early stages of MPD, the following features are seen:
• Generalized bone marrow proliferation with extension to long bones of limbs.
• Large number of marrow megakaryocytes which often have abnormal nuclei and occur in clusters.
• Increase fine fibrillar reticulin and sometimes, there is collagen deposition.
• Platelets dysfunction.

Polycythemia
It is a raised packed cells volume (PCV) above 51% in males and 48% in females. It is classified into:
• Absolute polycythemia : raised red cells mass.
1. Primary polycythemia.
2. Secondary polycythemia.
3. Idiopathic erythrocytosis.
• Apparent polycythemia: red cells mass is within normal.

Diagnostic criteria of polycythemia rubra vera (primary):
1. Red cell mass more than 25% above mean normal predicted value.
2. No evident cause for secondary polycythemia (with arterial O2 saturation above 92%).
3. Palpable splenomegally.
4. Evidence of clonal disorder e.g. abnormal marrow karyotype.
Diagnosis is made in presence of 1st and 2nd criteria with either 3rd or 4th one. But in absence of 3rd and 4th criteria then presence of any 2 of the following minor criteria can make diagnosis:
1. platelets count more than 400 ×109/L.
2. neutrophils count more than 10 ×109/L.
3. splenomegally by ultrasound (in absence of liver disease).
4. characteristic BFU-E growth or low serum erythropoietin level.

Causes of secondary polycythemia:
• Hypoxia with normal erythropoietin:
1. living at high attitude.
2. hypoxic lung diseases e.g. chronic obstructive lung disease (COPD).
3. cyanotic congenital heart diseases e.g. tetralogy of Fallot s.
4. smoking.
5. methemoglobinemia.
6. red cells metabolic defects.
• Inappropriate erythropoietin secretion:
1. renal tumor or ischemia.
2. hepatoma.
3. uterine fibroid.
4. bronchial CA.
5. pheochromocytoma.
• Miscellaneous causes:
1. neonatal polycythemia.
2. androgen therapy.
3. Cushing s disease.




Primary thrombocythemia
It characterizes by increased megakaryocytes proliferation in the marrow and raised circulating platelets count.

Clinical picture:
• Mean age at presentation is 60 years.
• 50% of patients are asymptomatic.
• Most common presenting symptom is vascular occlusion (thrombosis).
• Hemorrhage is another presenting feature, sometimes both thrombosis and hemorrhage in the same patient.

Diagnostic criteria:
1. platelets count more than 600 ×109/L.
2. no evidence of raised red cell mass.
3. negative Philadelphia chromosome.
4. no evidence supporting diagnosis of myelofibrosis.
5. no cause for reactive Thrombocytosis.

Causes of reactive Thrombocytosis:
1. acute bleeding.
2. inflammatory diseases e.g. rheumatoid arthritis.
3. malignancy.
4. infection.
5. post-operatively.
6. splenectomy.
7. exercise.
8. iron deficiency anemia.




Myelofibrosis
It is a clonal disease and fibrosis is secondary phenomenon. The criteria required for making diagnosis are:
1. Establishing that fibrosis is primary (i.e. it arises from intrinsic marrow disease rather than secondary to a systemic disease).
2. Distinguish myelofibrosis from other myeloproliferative disorders by these features.
• Huge splenomegally.
• Marrow fibrosis more than one third of adequate section of marrow biopsy.
• .Leuko-erythroblastic blood picture.
• Red cell mass isn t increased.
• Negative Philadelphia chromosome.
• Absence of systemic disorders.
The diagnosis of osteo-myelosclerosis requires the presence of sclerotic changes (detected by X ray) in the axial skeleton or long bones.
Systemic disorders that are associated with bone marrow fibrosis are:
1. Chronic myeloid leukemia.
2. Acute myeloid leukemia (AML-M7).
3. Myelodysplastic syndrome (MDS).
4. Hairy cell leukemia (HCL).
5. Metastatic CA.
6. Lymphomas (HD & NHL).
7. Systemic mastocytosis.
8. Chronic infections e.g. TB
9. Post radiation.
10. Exposure to chemicals e.