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MEH > When haemopoesis goes wrong > Flashcards

When haemopoesis goes wrong Flashcards

1
Q

what are myeloproliferative neoplasms (MPNs)

A

diseases of the bone marrow where excess cells are produced due to mutations in the precursors of myeloid lineage in bone marrow

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2
Q

what are the 4 major types of myeloproliferative neoplams

A
  • polycythaemia vera excess erythrocytes
  • essential thrombocythaemia overproduction of megakaryocytes leading to excess platelets
  • primary myelofibrosis initial proliferative phase followed by replacement of haematopoietic tissue by connective tissue leading to pancytopenia
  • chronic myeloid leukaemia excess granulocytes
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3
Q

what is polycythaemia

A
  • volume percent of erythrocytes in blood (haematocrit) exceeds 52% in males or 48% in females
  • high haematocrit and haemoglobin
  • increase can be due to increase in number of erythrocytes (absolute) or due to decrease in plasma volume (relative)
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4
Q

types of absolute polycythaemia

A

primary
- abnormality originates in bone marrow
- polycythaemia vera

secondary
- caused by increased levels of erythropoietin
- due to physiological response to hypoxia or abnormal production

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5
Q

clinical features of myeloproliferative disroders

A
  • overproduction of one or more blood elements
  • hypercellular marrow/marrow fibrosis
  • cytogenetic abnormalities
  • thrombotic and/or haemorrhagic diatheses
  • extramedullary haemopoiesis
  • potential to transform to acute leukaemia
  • overlapping clinical features
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6
Q

what is polycythaemia vera (PV)

A
  • arises from a myeloproliferative neoplasm in bone marrow resulting in overproduction of erythrocytes (and sometimes WBCs and platelets)
  • diagnosed by high haematocrit or raised red cell mass
  • ~95% caused by mutation in JAK2 gene so multipotent stem cells with the mutation survive longer and proliferate continuously
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7
Q

what is the JAK2 gene

A

janus kinase 2 gene
cytoplasmic tyrosine kinase that stimulates signalling pathways leading to erythrocyte production in response to erythropoietin

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8
Q

clinical features of polycythaemia vera (due to thicker blood)

A
  • thrombosis (venous and arterial)
  • haemmorhage (skin or GI tract)
  • headache and dizziness
  • plethora
  • burning pain in hands or feet (erythromelalgia)
  • pruritus
  • splenic discomfort, splenomegaly
  • gout
  • arthritis
  • may transform to myelofibrosis or acute leukaemia
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9
Q

treatment of polycythaemia vera (PV)

A
  • phlebotomy to maintain haematocrit below 45%
  • aspirin 75mg unless contraindicated
  • managing CVS risk factors
  • cytoreduction using hydroxycarbamides if poor tolerance of venesection, splenomegaly or other evidence of disease progression
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10
Q

secondary causes of polycythaemia vera

A

increased stimulation by erythropoietin
- high altitude living
- chronic hypoxia (severe COPD, long term cigarette use, cyanotic heart disease)
- renal disease
- tumours secreting EPO

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11
Q

what is essential thrombocythaemia

A
  • thrombocytosis (increase in platelet count) resulting from a myeloproliferative neoplasm
  • chronic blood cancer characterised by overproduction of platelets by megakaryocytes in bone marrow
  • ~50% caused by mutation in JAK2 gene
  • mutations in thrombopoietin receptor can also cause disease
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12
Q

types of thrombocytosis

A

primary
- abnormality originates in bone marrow
- essential thrombocythaemia

secondary
- normal bone marrow response to extrinsic stimulus e.g. infection, inflammation

redistributional
- platelets redistributed from splenic pool into bloodstream

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13
Q

common symptoms of essential thrombocythaemia

A
  • numbness in extremities
  • thrombosis (mostly arterial e.g stroke)
  • distrubances in hearing and vision (microvascular complications)
  • headaches
  • burning pain in hands or feet (erythromelalgia)
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14
Q

treatment of essential thrombocythaemia

A
  • patients classified as low and high risk for bleeding/blood clotting (based on age, medical history, blood count and lifestyle)
  • low risk = aspirin
  • high risk = hydroxycarbamide to reduce platelet count
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15
Q

what is (primary) myelofibrosis

A
  • proliferation of mutated haematopoietic stem cells results in reactive bone marrow fibrosis leading to replacement of marrow with scar tissue
  • mobilisation of mutated progenitor cells from bone marrow can causes cells colonise liver and spleen causing extramedullary haemopoiesis causing enlarged liver and spleen
  • associated with mutations on JAK2 gene
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16
Q

what is secondary myelofibrosis

A

when myelofibrosis has developed as a consequence of polycythaemia vera or essential thrombocythaemia

17
Q

symptoms of myelofibrosis

A
  • hepatosplenomegaly
  • bruising
  • fatigue
  • weight loss
  • fever
  • increased sweating
  • portal hypertension
18
Q

treatment for primary myelofibrosis

A
  • largely supportive and unsatisfactory as surivival ~5 years
  • hydroxycarbamide, folic acid and allopurinol
  • advanced disease may require blood transfusions and splenectomy
  • ruxolitinib (inhibitor of JAK2) shown to reduce spleen volume and improve symptoms
19
Q

difference between acute and chronic leukaemias

A

acute
- rapidly cause bone marrow failure
- large numbers of immature blast cells overwhelming ability of tissue to produce mature blood cells

chronic
- slow to cause symptoms
- often differentiation i.e. malignant clonal cell may be a mature cell

20
Q

what is chronic myeloid leukaemia (CML)

A
  • 15-25% of leukaemia in adults
  • unregulated growth of myeloid cells in bone marrow leading to accumulation of mature granulocytes (neutrophils) and myelocytes
  • very high WCC
21
Q

how does chronic myeloid leukaemia (CML) occur

A
  • chromosomal translocation called Philadelphia chromosome involving reciprocal translocation between chromosomes 9 and 22
  • causes oncogenic gene fusion (BCR-ABL) with tyrosine kinase activity that results on proliferation, differentiation and inhibtion of apoptosis
22
Q

treatment for chronic myeloid leukaemia

A
  • development of targeted cancer therapy through drugs that inhibit ATP-binding site of tyrosine kinase
  • oral drugs improved survival rates in CML patients
23
Q

what is aplastic anaemia

A
  • rare disease resulting in damage to bone marrow and haematopoietic stem cells leading to pancytopenia
  • inability of stem cells to generate mature blood cells
  • caused by genetic causes, autoimmunity or exposure to chemicals, drugs or radiation
24
Q

what is pancytopenia

A

deficiency in all three blood cell types
- red blood cells (anaemia)
- white blood cells (leucopenia)
- platelets (thrombocytopenia)

25
Q

causes of pancytopenia

A

reduced production
- B12/folate deficiency
- drugs - chemo, antibiotics
- viruses - EBV, HIV, viral hepatitis
- bone marrow infiltration by malignancy
- marrow fibrosis
- radiation
- idiopathic aplastic anaemia
- congenital bone marrow failure

increased removal
- immune destruction
- splenic pooling
- haemophagocytosis

26
Q

function of platelets

A
  • key role in haemostasis for clot formation
  • adhesion to damaged endothelial wall
  • activation change in shape from disc and release of granules
  • aggregation clumping together of more platelets to form plug
27
Q

what is thrombocytopenia

A

abnormally low level of platelets

28
Q

types of thrombocytopenia

A

inherited
- rare
- Fanconi anaemia, Bernard-Soulier syndrome, Alport syndrome

acquired
- decreased platelet production
- increased platelet consumption
- increased platelet destruction

29
Q

symptoms of acquired thrombocytopenia

A
  • bleeding gums
  • nosebleeds
  • heavier/longer menstrual periods
  • bruising
  • petechiae
30
Q

how can acquired thrombocytopenia arise

A

decreased platelet production
- B12/folate deficiency
- acute/aplastic leukaemia
- liver failure (less thrombopoietin)
- sepsis
- cytotoxic chemotherapy

increased platelet consumption
- massive haemmorhage
- disseminated intravascular coagulation (DIC)
- thrombotic thrombocytopenic purpura

increased platelet destruction
- autoimmune thrombocytopenic purpura
- drug induced eg. heparin
- hypersplenism leading to increase destruction and splenic pooling of platelets

31
Q

what is immune thrombocytopenic purpura (ITP)

A
  • autoimmune disease characterised by isolated thrombocytopenia that’s acute or chronic
  • presents due to symptoms if platelet count is very low or as incidental finding on blood count
  • fatal intracranial haemorrhage can occur (rare 1:500)
32
Q

causes of immune thrombocytopenic purpura (ITP)

A
  • anti-platelet autoantibodies
  • T cell activity against platelets and megakaryocytes
  • acute infection common in children
  • rheumatoid arthritis
  • systemic lupus erythematosus (SLE)
  • underlying lymphoid cancers
  • HIV
  • no obvious cause in 80% of adult cases
33
Q

treatment for immune thrombocytopenic purpura (ITP)

A

platelet transfusion don’t work as they get destroyed too
- corticosteroids
- immunosuppressive drugs
- intravenous pooled human immunoglobulin
- splenectomy
- thrombopoietin receptor agonists

MEH (26 decks)

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