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Myeloproliferative Disorders
Myeloproliferative disorders make up a group of chronic conditions
characterized by clonal proliferation of one or more marrow cell linage.
It is important to determine if it is clonal or not because if it isn’t clonal
that means it is a reactive.
process such as increasing RBC in hypoxia, increasing WBC in
infections, and increasing platelets
in haemorrhage.
Remember that the most physical sign in all myeloproliferative
disorders is the splenomegaly.
These disorders include:
1. Chronic myeloid leukaemia ‘CML’
2. Polycythaemia Vera ‘PRV’ in RBC.
3. Essential Thrombocythemia for the platelets.
4. primary Myelofibrosis
These disorders have possibility to
progression from one to another
e.g. PRV to Myelofibrosis, and may
be terminated to AML.
Polycythaemia Vera (PRV)
A neoplastic (clonal) stem cell disorder, leads to excessive
production of all myeloid cell lines, predominantly red cells.
Clinical features
The increase in whole blood viscosity causes vascular occlusion
and ischemia, compounded by the increase in platelets.
Headaches, Itch, Thrombosis, TIA, stroke, and Splenomegaly are
also findings.
Polycythaemia categories.
POLYCYTHAEMIA VERA.
SECONDARY POLYCYTHAEMIA.
HYPOXAEMIA PO2 < 92%
RENAL DISEASE
TISSUE HYPOXIA - HIGH AFFINITY HB
TUMOURS - HEPATOMAS, FIBROIDS, CEREBELLAR
HAEMANGIOBLASTOMAS
HIGH ERYTHROPOIET PRODUCTION
IDIOPATHIC ERYTHROCYTOSIS.
WHO criteria for PRV diagnosis.
Major criteria
1- Hemoglobin more than 18.5/dL in men and more then 16.5/ in women.
2-presence of JAK2 mutation.
Minor criteria
1-Bone marrow panmyelosis.
2-Low serum erythropoietin.
3-Endogenous colony formation in vitro.
Diagnosis requires both major and one minor or first major and two minor.
Bone marrow panmyelosis
Investigations of Polycythaemia
PULSE OXIMETRY
RENAL - URINALYSIS + RENAL ULTRASOUND
ABDOMINAL ULTRASOUND
NEUTROPHIL COUNT
PLATELET COUNT
MARROW CYTOGENETICS
MARROW EXAMINATION AND CULTURE
SERUM ERYTHROPOIETIN ASSAYS.
Essential Thrombocythemia (ET)
The malignant proliferation of megakaryocytes ,Constitutive
production of thrombopoietin by liver” results in a raised level of
circulating platelets those are often dysfunctional.
Prior to making a diagnosis of ET it is essential to exclude reactive
causes of increase platelets.
WHO Criteria for ET diagnosis.
1-Platelets count more than 450 000/cumm.
2-Megakaryocytic proliferation in the bone marrow.
3-Not meeting the criteria of other myeloproliferative disorders.
4-demostration of JAK2 mutation and in absence of JAK2 mutation,
there is no evidence of reactive thrombocytosis.
Diagnosis requires all these criteria.
Platelets more than 4500 000/ cumm in the peripheral blood
Megakaryocytic proliferation in the bone marrow
Clinical Features
Asymptomatic
Haemorrhage – 25%
Thrombosis – 20%
Splenomegaly – 30%
Recurrent Miscarriage
Primary Myelofibrosis
Background
Primary Myelofibrosis , first described by Heuck in 1879,
is a clonal disorder arising from the neoplastic
transformation of early hematopoietic stem cells.
primary Myelofibrosis is characterized by anaemia, bone
marrow fibrosis, extramedullary hematopoiesis,
leukoerythroblastosis, teardrop-shaped red blood cells
(RBCs) in peripheral blood, and hepatosplenomegaly
Diagnostic WHO criteria of primary myelofibrosis
Major criteria
1-Megakaryocytic proliferation with marrow fibrosis.
2-Not meeting the WHO criteria of other myeloproliferative disorders
3-Demonstration of JAK2 mutation.
Minor criteria
1-Leucoerythroblastosis.
2-Increased LDH level
3-Anaemia.
4-Splenomegaly.
Diagnosis requires all 3 major and 2 minor.
Peripheral blood shows teardrop cells and leukoerythroblastosis.
Bone marrow fibrosis
Extramedullary hematopoiesis in the spleen
Pathophysiology
The cause of the excessive marrow fibrosis observed in primary
myelofibrosis remains unclear.
Platelets, megakaryocytes, and monocytes are thought to secrete
several cytokines, such as transforming growth factor beta (TGF-β),
platelet-derived growth factor (PDGF), and basic fibroblast growth
factor (bFGF), which may result in fibroblast formation and
extracellular matrix proliferation.
In addition, endothelial proliferation and growth of capillary blood
vessels in the bone marrow are observed and may be a result of
TGF-β and bFGF production.
Clinical features
One fourth of patients with primary myelofibrosis are asymptomatic,
and the diagnosis is made as a result of detecting splenomegaly or
checking blood cell counts for an unrelated cause.
Symptoms may occur as a result of anemia, splenomegaly,
hypermetabolic states, extramedullary hematopoiesis, bleeding,
bone changes, portal hypertension, and immune abnormalities.
Anemia may occur as a result of ineffective erythropoiesis, erythroid
hypoplasia, and hypersplenism.
Splenomegaly may result in early satiety and left upper quadrant
discomfort. Splenic infarcts.
Physical signs
Splenomegaly is the most common finding in patients with primary
myelofibrosis, and it is present in approximately 90% of patients.
Hepatomegaly is also observed in 60-70% of patients with this
disease.
Pallor is observed in 60% of patients.
Other physical findings include petechiae and ecchymosis (20%),
lymphadenopathy (10-20%), signs of portal hypertension (10-18%),
and gout (6%).