L11: Heamatological changes in systemic disease Flashcards

1
Q

What can cause the blood to change in systemic disease?

A

Multifactorial

  • Underlying physiological or external cause
  • Complications of disease
  • Treatment- adverse effects
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2
Q

How can erythropoietin result in anaemias?

A

Reduced or dysfunctional erythropoiesis

  • -> lack of response in haemostatic loop
  • -> Bone marrow unable to respond to EPO
  • -> Other factors not present
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3
Q

What is the role of erythropoietin?

A

Hormonal control of erythropoiesis

Low blood O2–> Kidney hypoxia–> ↑ EPO production–> Bone marrow–> ↑RBC production–> high blood O2

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4
Q

What are the three contributors in anaemia of chronic disease?

A

Caused by inflammatory cytokines-

  • Iron dysregulation-> available iron not released for bone marrow use
  • Lack of response to EPO in bone marrow
  • Reduced lifespan of RBC
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5
Q

What is meant by functional iron deficiency?

A

Sufficient iron in the body but not available to the developing erythroid cells

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6
Q

What is the main source of iron in the body?

A

Recycled iron from old RBC

Require ferroportin

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7
Q

What is Hepcidin? What does it do? How is it regulated?

A
Peptide hormone released from the liver
Degrade ferroportin
-->Prevents absorbtion from gut
-->Prevents release from macrophages
HFE (homeostatic iron regulator), Transferrin receptors and inflammatory cytokines
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8
Q

How do chronic inflammatory conditions cause anaemia?

A
  1. Increased cytokines (IL-6), chemokines etc… released by immune cells
  2. Increase production of hepcidin by liver
  3. Inhibits ferroportin
  4. Decreased iron released from reticuloendothelial cells and absorption from gut
  5. Plasma iron reduced
  6. Inhibition of erythropoiesis in bone marrow
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9
Q

What are the causes of anaemia in chronic kidney disease (CKD)?

A

1- Reduced EPO –> due to kidney damage
2- Raised cytokines
3- Reduced clearance of hepcidin, increased hepcidin production due to inflammatory cytokines
4- Dialysis–> damage to RBC due to shear stress
5- Reduced lifespan of RBC–> uraemia (raised urea) (also inhibits megakaryocytes, low platelet count)

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10
Q

How is anaemia of chronic disease treated?

A
  • Treat underlying condition
  • If renal failure–> Recombinant human erythropoietin
  • Ensure Vit B12 and Folate stores adequate
  • Transfusion RBC if all else fails and patient symptomatic
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11
Q

What are the NICE guidelines on management of chronic kidney disease?

A

Reticulocyte Haemoglobin Content (CHr) to assess functional iron deficiency
Give iron if ferritin <200ug/L or CHr low
Iron given intravenously as problem with absorption

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12
Q

What are the haematological abnormalities in kidney disease?

A

Red blood cells
–> Anaemia (CKD, Blood loss, dietary, cancer)
–> Secondary polycythaemia (renal transplant, tumour, polycystic kidneys)
Neutrophils
–> Neutropenia (low) (Immunosuppression, post renal transplant, autoimmune kidney)
–> Neutrophilia (high) (inflammation, infection, drugs (steroid))
Platelets
–> Thrombocytopenia (low) (Uraemia inhibits production, drugs, haemolytic uraemic syndrome
–> High platelets (thrombocythemia) (inflammation, bleeding, iron deficiency)

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13
Q

What is Rheumatoid Arthritis?

A

Chronic immune mediated inflammatory condition

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14
Q

How is Rheumatoid Arthritis treated?

A

Pain relief usually NSAID
Disease Modifying Agents (DMARDs): corticosteroids, chemotherapy, monoclonal antibodies against cytokines (reduce inflammation)

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15
Q

How does Rheumatoid Arthritis cause anaemia?

A

Multifactorial
1- Anaemia of chronic disease
2- GI blood loss from NSAIDs and steroids
3- Autoimmune haemolytic anaemias

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16
Q

What are the haematological feature of Rheumatoid arthritis?

A

Disease active–> high platelets and neutrophils, CRP raised

Treatments, autoimmune reactions, hypersplenism–> Low platelets and neutrophils

17
Q

What is Felty’s syndrome?

A

Triad of diseases

  • -> Rheumatoid Arthritis -inflammation
  • -> Splenomegaly - englarged spleen
  • -> Neutropenia - Low neutrophil count
  • caused by splenomegaly contributing to peripheral destruction of neutrophils
  • failure of bone marrow to produce neutrophils, insensitivity of myeloid cells to stimulator GCSF
18
Q

How does chronic liver disease result in anaemias?

A
Portal hypertension, back pressure on spleen--> splenomegaly
Leads to:
- Splenic sequestration of cells 
- Overactive removal of cells
Low blood counts
19
Q

What are the haematological features of liver disease?

A

Portal hypertension–> oesophageal and gastric varices (dilated veins)–> bleeding
Blood loss made worse by:
- Deficiencies in coagulation factors–> Liver produces clotting factors, synthesis dependent on Vit K
- Endothelial dysfunction
- Thrombocytopenia
- Defective platelet function

20
Q

What causes the thrombocytopenia?

A
75% of pt
Impaired thrombopoietin
Splenic pooling of platelets
Increased destruction 
Reduced function--> contributes to bleeding
21
Q

What other cells are often seen in the liver disease?

A

Target cells
Increased chloesterol: phospholipid ratio
Membrane ‘baggy’

22
Q

What are some of the underlying causes of some of the other haematological features of liver disease?

A

1) Alcohol excess–> directly toxic to bone marrow cells–> pancytopenia
- -> secondary malnutrition common (folic acid deficiency)
2) Viral hepatitis–> bone marrow failure, hypoplatic or aplastic
3) Autoimmune liver disease–> Immune mediated anaemia, thrombocytopenia or neutropenia

23
Q

What haematological changes are seen post-operatively?

A

Red blood cells
- Anaemia –> Blood loss pre-op or during
- Temporary relative polycythaemia–> dehydration (rare)
Neutophils
- Neutropenia–> Sepsis
- Neutrophilia–> Post-op reactive, infection, severe bleeding
Platelets
- Thrombocytopenia –> drugs, sepsis, DIC
- Thrombocytosis–> Post-op reactive, infection, severe bleeding

24
Q

What haematological changes occur with infection?

A

Red blood cells
- Anaemia–> anaemia of chronic disease,
- Haemolytic anaemia (malaria)
Neutrophils
- Neutrophilia–> bacterial infection,
- Neutropenia –> severe bacterial infection, sepsis
- Eosinophilia–> parasitic infections
- Lymphocytosis and neutropenia–> Viral infections
Platelets
- Thrombocytosis–> Infection
- Thrombocytopenia–> severe infection, DIC in sepsis

25
Q

What is disseminated intravascular coagulation (DIC)?

A

Sepsis–> abnormal clotting
Coagulation activated pathologically
Numerous microthrombi form in circulation
Consumption of clotting factors and platelets
Consequence–> Microangiopathic haemolytic anaemia (MAHA)
Long clotting time, low fibrinogen, raised D dimers or fibrin degradations products
Risk of both bleeding and thrombosis

26
Q

What are the haematological changes seen in cancer?

A

Red blood cells
- Anaemia–> bleeding, iron deficiency, anaemia of chronic kidney disease, chemotherapy
- Polycythaemia–> EPO producing tumour
Neutrophils
-Neutropenia–> chemotherapy, marrow infiltrated by cancer cells
-Neutrophilia–> Inflammation, infection
Platelets
-Thrombocytopenia–> chemotherapy, sepsis, DIC, Marrow infiltrated
- Thrombocytosis–> Inflammation, infection, bleeding and iron deficiency

Increased risk of venous thrombosis

27
Q

What is a leucoerythroblastic film? What causes it?

A
Blood film--> immature RBC and WBC
Granulocyte precursors and nucleated RBCs seen on blood film
-Septic shock
-Bone marrow infiltration --> carcinoma or haematological malignancy
-Severe megoblastic anaemia
-Primary myelofibrosis (tear drop cells)
-Leukaemia
-Storage disorders