11. Haematology In Systemic Disease

Question 1

What are changes to the blood in systemic disease often caused by?

Answer 1

Underlying physiological or external cause - e.g. over expression of cytokines
Complications of the disease - e.g. ulcerative colitis
Treatment adverse effects - e.g. methotrexate

Question 2

In anaemia of chronic disease what are the 3 main contributors caused by inflammatory cytokines?

Answer 2

Iron dysregulation: available iron not released for use in bone marrow
Marrow shows lack of response to erythropoietin
Reduced lifespan of red cells

Question 3

What is anaemia of chronic disease?

Answer 3

Functional iron deficiency

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

Question 4

What is hepcidin regulated by?

Answer 4

HFE
Transferring receptor
Inflammatory cytokines

Question 5

What is the role of hepcidin and how does it work?

Answer 5

Prevents iron absorption from gut and prevents iron release form macrophages
Works by degrading ferroportin the protein involved in moving iron out of cells

Question 6

Describe anaemia of chronic kidney disease

Answer 6

Reduced erythropoietin production due to damage to kidneys
Underlying cause often associated with raised cytokines (makes more hepcidin)
Reduced clearance of hepcidin
Reduced lifespan of RBC as direct effect of uraemia

Question 7

What negative effect can dialysis have?

Answer 7

Damage to red blood cells

Question 8

What can uraemia cause?

Answer 8

Reduced lifespan of RBC

Inhibits megakaryocytes leading to low platelet counts

Question 9

What are the treatments for anaemia of chronic disease?

Answer 9

If associated with renal failure, recombinant human erythropoietin
Ensure vit B12 folate and iron stores are adequate
Transfuse red cells, only if all else fails and patient is symptomatic

Question 10

What are the possible haematological abnormalities in kidney disease related to red cells?

Answer 10

Anaemia - CKD, blood loss, dietary causes

Secondary polycythaemia - renal transplant, renal tumour, polycystic kidneys

Question 11

What are the possible haematological abnormalities in kidney disease relating to neutrophils?

Answer 11

Neutropenia - immunosuppression (post renal transplant), autoimmune kidney disease
Neutrophilia - inflammation, infection, drugs (steroids)

Question 12

What are the possible haematological abnormalities in kidney disease relating to platelets?

Answer 12

Thrombocytopenia - uraemia, many drugs, haemolytic uraemia syndrome
High - inflammation, bleeding, iron deficiency

Question 13

What is rheumatoid arthritis treated with?

Answer 13

Pain relief - often NSAIDs

Disease modifying agents - corticosteroids, chemotherapy, biological agents

Question 14

How is the haematology affected in rheumatoid arthritis?

Answer 14

High platelets and neutrophils when disease is active (CRP also up)
Low platelets and neutrophils may occur due to treatment, autoimmune reactions or to hypersplenism
Felty’s syndrome

Question 15

What is Felty’s syndrome?

Answer 15

Rheumatoid arthritis, splenomegaly and neutropenia
Neutropenia thought to be due to splenomegaly contributing to peripheral destruction of eutrophic and failure of bone marrow to produce neutrophils as insensitivity of myeloid cells to GCSF

Question 16

What can chronic liver disease cause?

Answer 16

Portal hypertension which causes splenomegaly which leads to splenic sequestration of cells and overactive removal of cells
Low blood counts

Question 17

What are the haematological features of liver disease?

Answer 17

Portal hypertension leads to oesophageal and gastric varies
Blood loss contributed to by deficiencies of coagulation factors, endothelial dysfunction, thrombocytopenia, defective platelet function

Question 18

Why does thrombocytopenia occur n patients with liver disease?

Answer 18

Impaired production as thrombopoietin is made in the liver
Splenic pooling
Increased destruction
Platelets made often have reduced function which contributes to bleeding

Question 19

What cells are often seen in liver disease?

Answer 19

Target cells, due to increased cholesterol:phospholipid ratio, membrane not as tight

Question 20

What is the effect of alcohol excess?

Answer 20

Directly toxic to bone marrow cells - can contribute to pancytopenia
Secondary malnutrition common (esp. folic acid deficiency) - leading to megaloblastic anaemia

Question 21

What is the effect of viral hepatitis?

Answer 21

Bone marrow failure can develop after an episode of hepatitis

Question 22

What is he effect of autoimmune liver disease?

Answer 22

Immune mediated anaemia
Thrombocytopenia
Neutropenia

Question 23

What post operative reactive changes can cause problem associated with red blood cells?

Answer 23

Anaemia - blood loss pre-op (trauma), blood loss during op

Temporary relative polycythaemia - dehydration (rare)

Question 24

What post operative reactive changes can occur relating to neutrophils?

Answer 24

Neutropenia - sever sepsis

Neutrophilia - post-op reactive, infection, severe bleeding

Question 25

What post operative reactive changes can occur relating to platelets?

Answer 25

Thromocytopenia - drugs, sepsis, DIC | Thrombocytosis - post-op reactive, infection, bleeding

Question 26

How can haematological changes with infection affect red blood cells?

Answer 26

Chronic infection can cause anaemia of chronic disease | Infection with malaria can cause haemolytic anaemia

Question 27

How can haematological changes with infection affect white blood cells?

Answer 27

Bacterial infection often associated with neutrophilia Severe bacterial infection/sepsis can cause neutropenia Parasitic infections associated with eosinophilia Viral infections can cause lymphocytes is and neutropenia

Question 28

How can haematological changes with infection affect platelets?

Answer 28

Infection can cause reactive thrombocytosis Severe infection can cause thrombocytopenia Thrombocytopenia may be associated with DIC in severe sepsis

Question 29

What is disseminated intravascular coagulation (DIC)?

Answer 29

Pathological activation of coagulation Numerous microthrombi are formed in circulation Consumption of clotting factors and platelets and a consequent microangiopathic haemolytic anaemia Long clotting times, low fibrinogen, raised D-dimers or fibrin degradation Risk of bleeding and thrombosis

Question 30

What does a blood film show of DIC?

Answer 30

Fragmented RBC Low platelets Immature RBC

Question 31

What are the haematological changes in cancer relating to red blood cells?

Answer 31

Anaemia - bleeding, iron deficiency, ACD, treatments (chemotherapy) Polycythaemia - EPO producing tumours

Question 32

What are the haematological changes in cancer relating to neutrophils?

Answer 32

Neutropenia - chemotherapy, marrow infiltrated by cancer cells Neutrophilia - inflammation, infection

Question 33

What are the haematological changes in cancer relating to platelets?

Answer 33

Thrombocytopenia - chemotherapy, sepsis, DIC, marrow infiltrated Thrombocytosis - inflammation, infection, bleeding, iron deficiency

Question 34

What is a leucoerythroblastic film?

Answer 34

Granulocyte precursors and nucleated RBC seen on blood film | Spilling out form marrow into blood when marrow is under stress

Question 35

When is a leucoerythroblastic film seen?

Answer 35

``` Sepsis/shock One marrow infiltration by carcinoma or haematological malignancy Severe megaloblastic anaemia Primary myelofibrosis (tear drop RBCs) Leukaemia Storage disorders ```