Myeloproliferative disorders

UST. Tamer Imad

UMST, Head of haematology
 MYELOPROLIFERATIVE
DISORDERS
The term myeloproliferative disorders
(MPDs) describes a group of
conditions arising from bone marrow
stem cells and characterized by clonal
proliferation
These diseasesofare :-
one or more
haemopoitic components
1.Polycythaemia . in the bone
marrow.
2.Myelofibrosis .
3.Essential thrombo.cythaemia .
The disorders occurred due to there a
single acquired mutation of the cytoplasmic
tyrosine kinase Janus –associated kinase
2(JAK2) in the marrow and blood.
POLYCYTHAEMIAS
It is a raised packed cell volume (PCV)
>51 in males and 48 in females, with
increase in red cell mass above normal
range.
It can be 2 groups according to the
RCM:-
1-Absolute polycythaemia in which the
red cell mass (RCM) is above the normal
-:ABSOLUTE POLYCYTHAEMIA -1

Also known as true polycythaemia.

Divided into two groups :-
I. Polycythaemia vera .
II. Secondary polycthaemia .
POLYCYTHAEMIA VERA (RUBRA
VERA) :-
 It is a primary polycythaemia .
 It is a chronic, progressive and fatal disease,
in which the abnormality is an excess
production of the former element of blood
by hyperplastic BM.
 There is an apparent reduction in the
plasma concentration of erythropoietin in
response to the elevated PCV .
CLINICAL FEATURES:-

 Headaches.
 Plethoric appearance.
 Spleenomegaly.
 Hypertension.
 Peptic ulcer.
 Gout.
LABORATORY FINDING OF
:RUBRA VERA
•Marked increase in red cell mass; red cell count
exceed 7×1012/l .
•Hb raised : >18.0 g/dl .
•Pcv about 60 – 61%
•50% of patients showed increase in TWBC
mainly neutrophils, eosinoplils and basophils .
•2/3 of the patients showed increase platalets .
•Neutrophil alkaline phosphatase is increase .
•BM is hypercellular. Erythropoiesis,
granulopoiesis, and numbers of
megakaryocytes are all variably increase .
•The course of the disease : the disease is
often advanced when first detected, but may
run a prolonged course .
•Some patients can develop myelofibrosis or
acute leukaemia.
 SECONDARY
POLYCYTHAEMIA.
•A variety of uncommon, well-recognized, disorders
caused an increase erythropoietin secretion and
absolute polycythaemia .
•Patients may presents due to the underlying
pathology, or with an unexplained polycythaemia
Causes :-
1- Hypoxia :-
•High altitude : compensatory erythrocytosis that
develops in high altitude due to inadequate
oxygenation of blood as a result of the low
-Congenital heart disease :-
•Secondary polycythaemia develops in cyanotic
congenital heart disease because of shunting of blood
from the right to the left side of the heart .
-Chronic pulmonary disease :-
•It occur in some lung diseases in which there is
interference with oxygenation of pulmonary blood,
producing lower arterial oxygen saturation
-Smoking .
 2-Inappropriate erythropoietin secretion:-
-Renal disorders :-
-Liver diseases :

2- Relative polycythaemia:-
•Dehydration.
•Redistribution of body fluids.
 Primary
thrombocythaemia
•It is a clonal disorder involving a multipotent stem
cells, characterized by megakaryocytic proliferation in
the BM and raised circulating platelet numbers .
Synonyms include :-
Essential thrombocythaemia .
Primary haemorrhagic thrombocythaemia .
•It can be asymptomatic or presented with vascular
occlusive and haemorrhagic .
aboratory finding :-

•Platelets count is raised in the range of 600-

2500×109/l .
•Two-third of patients show reduced platelet
aggregation, 20% have evidence of hypo-and hyper-
aggregation .
•Reduced dense bodies and α-granules contents of
platelets has been shown .
•Plasma high molecular weigh v-WF multimers and
ristocetin cofactor are reduced .
•The Hb and PCV are normal or modestly reduced .
•The red cell morphology is normal .
•WBC is increase above 12×109/l. occasionally
eosinophilia or basophilia .
•Marrow aspiration is difficult, aspirated material
reveals aggregated platelets .
•Trephine sections show hypercellularity with
decreased fat spaces. There is marked increase in
megakaryocytes which are typically larger and have
a greater nuclear segmentation, they are often in
clusters .
•There is increase in reticulin .
 Myelofibrosis

•It is a disease of old age group, characterized by

increase fibroblastic activity in the haemopoietic
marrow resulting in great increase in reticulin and
collagen fibres.
•It is a primary disorder .
•Chronic granulocytic leukaemia and polycythaemia
vera may transform to myelofibrosis .
Pathogenesis :-
•Proliferation of connective tissue element within
the BM is a constant feature .
•There is an increase in reticulin fibres with
progressive collagen deposition .
•This collagen is principally type III .
•Simultaneously, there is increasing marrow
vascularity and increase collagen type IV .
•Chronic myelofibrosis may be accompanied by new
bone formation .
Laboratory finding :-

•The peripheral blood film shows :-

•Leucoerythroblastic changes, with a large number
of nucleated red cells .
•Anisocytosis and poikiolocytosis, with tear-drop red
cells, macrocytosis may occur .
•WBC count may be normal, elevated, or decrease .
•The platelet count is also variable .
•Platelet function is defective in up to 50% of
patients .
•Bone marrow aspiration is usually unsuccessful,
(dry tap ) .
•Trephine biopsy is essential for diagnosis .
•Morphological features in the bone marrow:-
•At first, there is hyperplasia of all hemopiotic cells,
usually with a normal distribution .
•At a later stage, there are decreasing numbers of
haemopoietic cells with an increase fat contents and
this is accompanied by increasing fibroblastic
proliferation .