Haematology in systemic disease Flashcards
Physiological life cycle of blood cells
Blood cells made in bone marrow—> sent out to the periphery and then removed by the spleen (reticulocytes-endothelial system)
Haematological changes associated with
- Anaemia of chronic disease and anaemia of renal disease
- Rheumatoid arthritis
- Liver disease / alcohol excess
- Post-operative state and infection
- Cancer
Changes to the blood is systemic disease are often multi-factorial due to…
- Physiological causes e.g. inflammatory cytokines (IL-6)
- Complications of the disease
- e.g. UC loss of blood and unable to absorb nutrients
- Treatment- adverse effects e.g. methotrexate
Anaemia results due to
-
Lack of response from haemostatic loop
- E.g. in chronic kidney disease the kidney stops making EPO
-
Bone marrow unable to respond to EPO
- E.g. after chemotherapy, toxic insult or infections (parvovirus)
- In anaemia of chronic disease e.g. rheumatoid arthritis, iron is not made available to marrow for RBC production
which cells produce erythropoietin in response to hypoxia
pericytes in the kidney
EPO binds to
receptros on erythroblasts in bone marrow and stimualtes red cell production
anaemia of chronic disease: examples of chronic disease
Rheumatoid arthritis, IBD, chronic infections e.g. TB
mode of actiom of anaemia of chronic disease
IL- 6 released by immune cells due to inflamamtory condition
- increased production of hepicidin by the liver
- hepcidin
- inhibits ferroprotion
- decreased iron release from RES
- decreased iron absorption in the gut
- leads to plasma iron reduced
- inhibits ferroprotion
- plasma iron reduction leads gto inhibition of EPO in bone marrow –> anaemia
anaemia of chronic disease leads to what sort of iron deiciency
Functional iron deficiency- sufficient iron in the body but not available to develop erythropoiesis cells
à due to hepcidin
hepcidin prevents
iorn release from macrophages and iron absorption from the gut
anaemia of chronic kidney disease
- Kidney becomes damaged and less functional throughout disease
- Will need renal replacement therapy e.g. dialysis or intraperitoneal dialysis
- Underlying cause of CKD often associated with raised cytokines
- Reduced clearance of hepcidin and increase hepcidin production due to inflammatory cytokines
- Dialysis- damages red blood cells- shear stress e.g. of the dialysis tubing
- Reduced lifespan of RBC as a direct effect of uraemia - high levels of urea
- Ureamia also inhibits megakaryocytes- leading to low platelet count
ureamia
inhibits megakaryocytes leading to low platelet count
Treatment of anaemia of chronic disease
*
- Treat underlying condition
- Associated with renal failure
- Give recombinant human EPO
- Ensure Vit B12 folate and iron stores are adequate
- Transfuse red cells- only if all else fails and patient symptomatic
- Absorption given in IV form due to absorption being impaired
with A of CKD what csan be used to assess function iron deficiency
reticulocyte haemoglobin content
how to treat A of CKD low iron
give ferritin
- iron should be given in intravenous form as absorption
possible haematological abnormalities in kidney disease
3. Rheumatoid arthritis
A chronic immune mediated inflammatory condition
treatment of RA
- Pain relief (NSAIDS)
- Disease modifying agents (DMARDs)
- Corticosteroids
- Chemotherapy e.g. methotrexate
- Biological agents – monoclonal antibodies against cytokines
features of RA
- Anaemia is multifactorial
- ACD
- GI blood loss due to NSAIDS and steroids
- Risk of autoimmune haemolytic anaemia
- High platelets and neutrophils when disease is active (CRP will also be up)
- Low platelets and neutrophils may occur due to treatment, autoimmune reactions or to hypersplenism (splenomegaly can occur in this condition)
- Feltys syndrome
Felty’s syndrome
Triad: Rheumatoid arthritis, splenomegaly and neutropenia
- Neutropenia due to splenomegaly contributing to peripheral destruction of neutrophils and failure of bone marrow to respond to GCSF (myeloid cell stimulator)
liver disease
Chronic liver disease will cause portal
hypertension which causes splenomegaly
which leads to:
- Splenic sequestration of cells
- Overactive removal of cells
- Low blood count
Haematological features of liver disease
Thrombocytopenia in 75% of patients
- Impaired production of thrombopoietin is made in the liver
- Splenic pooling
- Increased destruction
- Those platelet made often have reduced function which contributes to bleeding
*Target cells often seen in liver disease- due to increased cholesterol: phospholipid ratio
why does chronic kliver diseas elead to splenomegaly
portal hypertneson
Portal hypertension also leads to
oesophageal and gastric varices (dilated veins prone to bleeding due to higher than normal pressure)
- Most clotting factors are made by the liver, synthesis of some dependent on vitamin k- patients will become quickly deficiency in clotting factors
blood loss in chronic liver disease contributed to by
- Deficiencies of coagulation factors
- Endothelial dysfunction
- Thrombocytopenia
- Defective platelet function
Other haematological features of liver disease are depending on the underlying cause
Alcohol excess
- Directly toxic to bone marrow cells- pancytopenia
- Secondary malnutrition – folic acid deficiency
Viral hepatitis
- Bone marrow failure (hypoplastic/aplastic marrow) can develop after hepatitis
Autoimmune liver disease
- Immune mediated anaemia, thrombocytopenia or neutropenia
5. Post operative reactive changes
6. Haematological changes with infection
Red blood cells- chronic infection can cause anaemia of chronic disease e.g. malaria can cause haemolytic anaemia
neutrophil reaction to bacterial infection
- Neutrophilia- associated with bacterial infections
- Neutropenia- associated with severe bacterial infection/sepsis
neutrophil reaction to paracytic infection
eosinophilia
neutrophil reaction to viral infection
lymphocytosis and neutropenia
thrombocytes and infection
- Infection can cause reactive thrombocytosis
- Severe infection can cause thrombocytopenia
- Thrombocytopenia may be associated with with disseminated intravascular coagulation (DIC) in severe sepsis
Sepsis can lead to clotting abnormalities- disseminated intravascular coagulation (DIC)
- Pathological activation of coagulation
- Numerous microthrombi are formed in the circulation
- Consumption of clotting factors and platelets and a consequence microangiopathic haemolytic anaemias (MAHA)
- Clotting tests
- Clotting time ling
- Low fibrinogen
- Raised D-dimers
- Risk of both bleeding and thrombosis
Leucoerythroblastic film
*
Granulocyte precursors and nucleated RBC seen on blood film
- Spilling out from the marrow into the blood when the marrow is under stress
- Sepsis
- Bone marrow infiltration by carcinoma or haematological malignancy
- Severe megaloblastic anaemia
- Primary myelofibrosis
- Leukaemia
- Storage disorder
haematological changes in cancer
