When Haemopoiesis goes wrong Flashcards
What are Myeloproliferative neoplasms?
Group of diseases of Bone Marrow in which excess cells are produced (Cancers)
How do Myeloproliferative neoplasms arise?
Genetic mutations in the precursors of the myeloid lineage in the bone marrow
4 Major Types of Myeloproliferative neoplasms
-POLYCYTHAEMIA VERA (excess erthyrocytes)
-ESSENTIAL THROMBOCYTHAEMIA (Overproduce Megakaryocytes - too many platelets)
-PRIMARY MYELOFIBROSIS (Haematopoietic tissue replaced by connective tissue, generation of blood cells impaired PANCYTOPENIA OCCURS)
-CHRONIC MYELOID LEUKAEMIA (excess Granulocytes)
What is Polycythaemia?
Disease state
When volume percent of erythrocytes in blood (Haematocrit) exceeds:
-52% males
-48% females
What is Absolute Polycythaemia ?
How can it be caused?
Increase in the number of erythrocytes increases % RBC in blood
Primary - Bone marrow abnormality
Secondary - Increased erythropoietin
Relative Polycythaemia
Decrease in plasma volume causing increased % of Erythrocytes in blood
What Gene mutation causes (Primary) Polycythaemia Vera? (PV)
Mutation in JAK2 gene
Clinical Features associated with Polycythaemia vera basically from blood being thicker
Thrombosis
Haemorrhage
Headache dizziness
Splenomegaly
Gout
burning pain in hands and feet
Most common cause of morbidity and death associated with Polycythaemia Vera is?
Thrombosis
What is thrombosis?
When blood clots block arteries or veins
Treating Thrombosis
Phlebotomy (removing excess erythrocytes)
Aspirin (has anti-platelet effect)
Hydroxycarbamide (Inhibitts DNA synthesis and so replication)
What is secondary Polycythaemia?
Increase percentage of erythrocytes in blood due to increased production of ERYTHROPOIETIN
What are the Causes of Secondary Polycythaemia?
Something that leads to increased production of Erythropoietin
Chronic Hypoxia (living at high altitude, severe COPD, heavy cigarette use or cyanotic heart disease)
Renal disease
Tumours releasing Erythropoietin
What is Thrombocytosis?
Increased platelet count (above normal range)
Thrombocytosis is common reaction to
Infections
Inflammation
Thrombocytosis that is caused by a Myeloproliferative neoplasm is called
Essential Thrombocythaemia
What is Essential Thrombocythaemia?
Chronic blood cancer (myeoproliferative neoplasm)
Overproduction of platelets due to overproduction of Megakaryocytes
What causes Essential thrombocythaemia?
Mutations in JAK2 genes
Mutations in Thrombopoietin receptor
Symptoms of Essential Thrombocythaemia
Numbness of extremities
Thrombosis (stroke/peripheral gangrene)
Hearing and Vision disturbances (microvascular complications)
Head aches
Burning pains of hands and feet (Erythromelalgia)
Treating for Essential Thrombocythaemia
Low risk = Aspirin (anti-platelet properties)
High risk = Hydroxycarbamide
Anything that reduces platelet count
What is Thrombocytopenia?
Lower than normal range of platelets
Opposite of Thrombocythaemia/thrombocytosis
Inherited or Aquired
The general principles that causes Aquried thrombocytopenia?
Decreased platelet PRODUCTION
Increased platelet CONSUMPTION
Increased platelet DESTRUCTION
What is Immune thrombocytopenia purpura (ITP)
Autoimmune disease that causes Thrombocytopenia
Antiplatelet auto antibodies bind to platelets
T cell activit against platelets and megakaryocytes
What is Primary myelofibrosis?
Myeloproliferative neoplasm where proliferation of mutated Haematopoietic stem cells then cause replacement of bone marrow with scar tissue (collagen)
Why does Primary Myelofibrosis often show enlarged liver and spleen?
Mutated bone marrow progenitor cells migrate to liver and spleen (extramedullary haematopoiesis)
What causes Primary Myelofibrosis?
Often mutations of JAK2 genes
What is Secondary Myelofibrosis/when does it occur?
When myelofibrosis has occurred as a result of Polycythaemia Vera or essential thrombocythaemia
Symptoms of primary myelofibrosis
Hepatosplenomegaly
Bruising
Fatigue (anemia symptoms)
Weight loss
Fever
Portal hypertension
Treatment for Primary myelofibrosis
Mainly supportive
Hydroxycarbamide
Folic acid (help prevent anaemia)
Splenectomy
ruxolitinib (inhibitor of JAK2)
Thinking about Leukaemia Types
Acute or Chronic and what lineage do the abnormal malignant cells arise from
Acute leukaemias
Large number of immature blast cells overwhelm ability of bone marrow to make mature blood cells
Rapid bone marrow failure
Chronic leukaemias
Slow to cause symptoms
Often as a result of a differentiated cell being malignant
What is Chronic Myeloid Leukaemia?
Unregulated growth of myeloid cell in bone marrow
Causes accumulation of mature Granulocytes (mainly neutrophils)
What causes Chronic myeloid leukaemia?
Chromosomal translocation called PHILADELPHIA CHROMOSOME
What occurs as a result of the Philadelphia chromosome?
Oncogenes gene fusion with tyrosine kinase activity
Proliferation, differentiation and inhibition of apoptosis
What is Aplastic anaemia?
Damaged bone marrow and hematopoietic stem cells
Causes PANCYTOPENIA
Aplastic meaning
Inability of stem cells to generate mature blood cells
What can cause aplastic anaemia?
Autoimmunity
Chemicals
Drugs
Radiation
What is a neoplasm?
A Cancer
