Myeloproliferative Disorders

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Myeloproliferative Disorders
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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 isnt 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.
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• These disorders include
• 1. Chronic myeloid leukaemia CML
• 2. Polycythaemia Vera PRV in RBC.
• 3. Essential Thrombocythemia for the platelets.
• 4. primary Myelofibrosis

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• These disorders have possibility to
• progression from one to another
• e.g. PRV to Myelofibrosis, and may
• be terminated to AML.

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• 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.

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• Polycythaemia categories.
• POLYCYTHAEMIA VERA.
• SECONDARY POLYCYTHAEMIA.
• HYPOXAEMIA PO2 lt 92
• RENAL DISEASE
• TISSUE HYPOXIA - HIGH AFFINITY HB
• TUMOURS - HEPATOMAS, FIBROIDS, CEREBELLAR
• HAEMANGIOBLASTOMAS
• HIGH ERYTHROPOIET PRODUCTION
• IDIOPATHIC ERYTHROCYTOSIS.

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• 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.

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• Bone marrow panmyelosis

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Investigations of Polycythaemia

• PULSE OXIMETRY
• RENAL - URINALYSIS RENAL ULTRASOUND
• ABDOMINAL ULTRASOUND
• NEUTROPHIL COUNT
• PLATELET COUNT
• MARROW CYTOGENETICS
• MARROW EXAMINATION AND CULTURE
• SERUM ERYTHROPOIETIN ASSAYS.

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• 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.

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• 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.

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• Platelets more than 4500 000/ cumm in the
  peripheral blood

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• Megakaryocytic proliferation in the bone marrow

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• Clinical Features
• Asymptomatic
• Haemorrhage 25
• Thrombosis 20
• Splenomegaly 30
• Recurrent Miscarriage

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• Primary Myelofibrosis

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• 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

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• 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.

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• Peripheral blood shows teardrop cells and
  leukoerythroblastosis.

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• Bone marrow fibrosis

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• Extramedullary hematopoiesis in the spleen 

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• 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-ß),
  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-ß
  and bFGF production.

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• 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.

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• 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).