Haem in systemic disease and infection

Question 1

factors that contribute to anaemia of chronic disease

Answer 1

Blood loss (Iron deficiency)				Poor nutrition (folate, B12 deficiency)			Immune
Red cell fragmentation (microangiopathic)

Question 2

essential characteristics of anaemia of CD

Answer 2

Disordered Iron Metabolism
Reduced Red Cell Lifespan
Reduced BM response to Erythropoietin

Question 3

what is hepcidin

Answer 3

Iron regulatory protein: negative regulator of iron absorption from gut and release from macrophages. Inhibits ferroportin

Hepcidin is to iron, what insulin is to glucose

Question 4

what is ferroportin

Answer 4

transmembrane protein responsible for transporting iron from inside the cell to outside

Question 5

what stimulates hepcidin

Answer 5

iron

inflammation

Question 6

what inhibits hepcidin

Answer 6

hypoxia- erythropoiesis
testosterone and E2
GFs

Question 7

Ix of anaemia of chronic disease

Answer 7

Normochromic, normocytic anaemia (may become microcytic)
Iron bonding studies: Low serum iron, low transferrin saturations, reduced TIBC (total iron binding capacity), increased ferritin
Adequate to increased macrophage iron stores (iron stain on bone marrow sample)
Reduced iron absorption from gut and sequestration of iron in reticuloendothelial system

Question 8

why is ferritin increased in anaemia of chronic disease?

Answer 8

Ferritin is increased because it is increased in inflammatory conditions as well as being an indicator if iron stores- can be very misleading

Question 9

why is iron metabolism disordered in anaemia of CD

Answer 9

Hepcidin levels increased 100 fold

Causes low serum iron & replete macrophages

Occurs within hours of acute phase response

Key is also acute phase response results
Raised ferritin, C-reactive protein (IL-6), FVIII,platelets
Clinical history

Question 10

key differences between ACD and iron def anaemia

Answer 10

ACD: normal/low MCV, IDA: low MCV

ACD: TIBC reduced, IDA: TIBC increased

ACD: ferritin normal/increased
IDA: ferritin reduced

ACD: BM iron stores present
IDA: BM iron stores absent

ACD: hepcidin increased
IDA: hepcidin normal

ACD ESR: increased
IDA: ESR normal

Question 11

why is TIBC low in ACD

Answer 11

less transferrin produced (but more ferritin), aim to reduce availability of iron for pathogens. This is mainly regulated by increased hepcidin production.

Question 12

elements of haemolysis that can be seen on tests

Answer 12

Unconjugated hyperbilirubinaemia, -RBC fragments, -Raised LDH,
-Increased reticulocytes

Question 13

causes of reduced red cell lifespan

Answer 13

-Immune mediated – activation by underlying infection and activation of complement and immune cascade positive DAT

Non –immune: medication, renal failure, MAHA

Question 14

conditions that can cause ACD

Answer 14

Anaemia of Inflammation
Infection: TB, bacteria, 
Cancer
Autoimmune & connective tissue disease: Vasculitis, SLE
CKD
Congestive heart disease

Question 15

tx of ACD

Answer 15

Principles
Treat the underlying cause
Treat associated factors

Treatments
Iron supplementation
Intravenous, Oral, success of getting into erythroblasts, 
Is there a risk of feeding infection
Trial of EPO (Renal disease)
Blood transfusions (If symptomatic)

Question 16

other haematological changes in chronic disease

Answer 16

Leukocytosis: infection & inflammation
Neutrophilia (bacterial)
Lymphocytosis (viral)

Leukopenia: infection consumption, reduced production

Platelet increase: Thrombocytosis
acute phase response

Platelet decrease: Thrombocytopenia
	Immune mediated
	Drug mediated
	Consumption (Hypersplenism and DIC)
	Affects from specific infections

Question 17

define DIC

Answer 17

characterised by systemic activation of pathways leading to and regulating coagulation, which can result in the generation of fibrin clots that may cause organ failure with concomitant consumption of platelets and coagulation factors that may
result in clinical bleeding