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 1
st
and 2
nd
criteria
with either 3
rd
or 4
th
one. But in absence of 3
rd
and 4
th
criteria then presence of any 2 of the following minor
criteria can make diagnosis:
1.
platelets count more than 400 ×10
9
/L.
2.
neutrophils count more than 10 ×10
9
/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 ×10
9
/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.g. benzene.