Haematology Session 4 Flashcards
Why can changes to the blood occur in systemic disease?
- Underlying physiological causes (eg. abnormal cytokines)
- Complications of the disease
- Adverse treatment effects
Why might anaemia develop in chronic kidney disease?*
- Damaged kidney stops making erythropoietin
- No response in haemostatic loop
Why can anaemia happen in cancer patients/patients with infections?*
Bone marrow not able to respond to erythropoietin and therefore can’t produce RBCs
What is a functional anaemia?
- Anaemia of chronic disease
- Iron is sufficient but is not made available to the bone marrow for RBC production.
What are the 3 contributors to anaemia of chronic disease, and what are they caused by?
- Available iron not released
- Lack of response to erythropoietin
- Reduced red cell lifespan
All caused by inflammatory cytokines.
What is meant by a functional iron deficiency?
There is sufficient iron available in the body, but it is not available to the developing erythroid cells.
What transporter is needed to recycle iron from old/broken down erythrocytes?
Ferroportin.
What is hepcidin regulated by?
- HFE
- Transferrin receptor
- Inflammatory cytokines
What is inhibited when ferroportin is degraded?
- Iron release from macrophage
- Iron absorption from gut
How is iron dysregulated in anaemia of chronic disease?*
Production of hepcidin by the liver acts on ferroportin, preventing the release of ferric iron out of the cell.
What is the process through which anaemia develops in chronic inflammation?*
- Inflammation causes cytokines to be released by immune cells
- Cytokines stimulate hepcidin production in liver
- Ferroportin inhibited
- Iron not released from reticuloendothelial system
- Iron not absorbed in gut
- Inhibition of erythropoiesis
= ANAEMIA
What are the factors contributing to anaemia of chronic kidney disease?
- Damaged kidneys produce less erythropoietin
- Reduced hepcidin clearance
- Increased cytokines = more hepcidin produced
- Dialysis damages red blood cells
- Uraemia reduces RBC lifespan and inhibits megakaryocytes
How to treat anaemia of chronic disease when it’s associated with renal failure?
- Recombinant human erythropoietin (intramuscular injection)
- Ensure that Vit B12, folate and iron are adequate
- Transfusion if other doesn’t work and symptoms present
How to assess for functioning iron deficiency?
Use reticulocyte haemoglobin content (CHr)
Why should iron be given in IV form in anaemia of chronic renal failure?
Absorption is impaired
When should iron be given?
- Ferritin below <200micrograms/L or low CHr
What are the haematological abnormalities of red cells in kidney disease?
- Anaemia: blood loss, etc
- Secondary polycythaemia: renal transplant/tumour
What are haematological abnormalities of neutrophils in kidney disease?
Neutropenia: immunosuppression (post transplant), autoimmune kidney disease
Neutrophilia: inflammation, infection, steroids
What are possible haematological abnormalities of platelets in kidney disease?
Thrombocytopenia: uraemia, drugs, haemolytic uraemic syndrome (acute kidney injury)
Thrombocythaemia: Inflammation, bleeding, iron deficiency
What is rheumatoid arthritis?
A chronic immune mediated inflammatory condition.
What are the now rarely seen changes to hands in rheumatoid arthritis?*
- Boutonniere thumb deformity
- Ulnar deviation of metacarpopharyngeal joint
- Swan neck finger deformity
What is rheumatoid arthritis treated with?
- NSAIDs (pain relief)
- Corticosteroids and chemotherapy (disease modifying, slow progression)
- Monoclonal antibodies against cytokines for patients with very active rheumatoid arthritis
Why can NSAIDs cause blood loss?
Prolonged use can cause GI bleeding.
Why can high platelets, neutrophils and CRP occur in rheumatoid arthritis but also low platelets and neutrophils?
- High platelets, CRP and neutrophils when the disease is active due to inflammation
- Low platelets and neutrophils due to treatment and autoimmune reaction to hypersplenism
What is Felty’s syndrome?*
- Triad of arthritis, splenomegaly and neutropenia
- Splenomegaly may destroy neutrophils
- Insensitivity of myeloid cells to GCSF (granulocyte colony stimulating factor)
Why does chronic liver disease cause portal hypertension and therefore splenomegaly?
- Vessels in liver are damaged/blocked off
- Blood redirected through the portal system, therefore hypertension
- Causes splenomegaly and trapping of red cells, platelets and white cells in spleen = pancytopenia
Why can alcohol abuse cause megaloblastic anaemia?
It’s a common cause of folic acid deficiency.
What can portal hypertension lead to?
- Higher pressure = distended vessels
- Oesophageal and gastric varices
- More prone to bleeding and are a leading death cause
Why are patients in liver disease deficient in clotting factors?
- Most made by the liver
- Synthesis of some dependent in vitamin K (also deficient in patients with liver damage
Why is thrombocytopenia present in most patients with liver disease?
- Impaired production (made in liver)
- Splenic pooling
- Increased destruction
- Reduced function
Why are target cells seen often in liver disease?*
Increased cholesterol:phospholipid ratio.
What are haematological features of liver disease due to alcohol excess?
- Pancytopenia (directly toxic to BM)
- Secondary malnutrition - folic acid deficiency
What are haematological features of liver disease due to viral hepatitis?
Bone marrow failure
What are haematological features of autoimmune liver disease?
- Neutropenia
- Thrombocytopenia
- Immune mediated anaemia
Why can anaemia be present post-operatively?
- Blood loss pre and post operation
Why can neutropenia and neutrophilia be present post operatively?
- Neutropenia: severe sepsis
- Neutrophilia: bleeding, infection
Why can thrombocytosis and thrombocytopenia occur postoperatively?
Thrombocytosis: infection, bleeding
Thrombocytopenia: drugs, sepsis, DIC
What is bacterial infection usually associated with?
Neutrophilia
What is severe bacterial infection usually associated with?
Neutropenia
What are parasitic infections associated with?
Eosinophilia
What are viral infections associated with?
Lymphocytosis and neutropenia
What is disseminated intravascular coagulation (DIC)?*
- Pathological activation of coagulation (continued when not needed)
- In severe sepsis
- Microthrombi formed in circulation
- Consumption of clotting factors and platelets
- Microangiopathic haemolytic anaemia (MAHA)
- Long clotting, low fibrinogen and higher fibrin degradation products
- Risk of bleeding (low platelet) and thrombosis (cut off circulation)
What types of cells are usually present in DIC?*
- Schistocytes
- Low platelets
What cells are seen in patients post-splenectomy?
- Howell-Jolly bodies
- Thrombocytosis and lymphocytosis
What are the causes of anaemia and polycythaemia in cancer?
Anaemia:
- Bleeding
- Iron deficiency
- Chemotherapy
- Infiltration of bone marrow by cancer cells
- Anaemia of chronic disease
Polycythaemia:
- Tumours that produce erythropoietin (eg. adrenal tumour)
Why can cancer cause neutropenia and neutrophilia?
Neutropenia:
- Chemotherapy
- Marrow infiltration by cancer
- HIGH VULNERABILITY TO SEPSIS
Neutrophilia:
- Inflammation
- Infection
What are causes of thrombocytopenia and thrombocytosis in cancer?
Thrombocytopenia:
- Sepsis
- DIC
- Marrow infiltration
Thrombocytosis:
- Inflammation
- Bleeding
- Iron deficiency
Why are people with cancer at a higher risk of deep vein thrombosis and pulmonary emboli?
- Increased clotting
- Inflammation
What is often seen when the marrow is infiltrated by cancer cells?*
Leucoerythroblastic film - immature red and white cells due to spilling out from the marrow when under stress.
When else are leucoerythroblastic films seen?
- Sepsis
- Megaloblastic anaemia
- Primary myelofibrosis
- Leukaemia
