Haematology In Systemic Disease Flashcards
What could cause haemopoietic changes in systemic disease?
Often multifactorial. You need to look at the cause, complications and treatment.
What is anaemia of chronic disease?
Diserythropoiesis (Not enough red blood cells made).
What can cause anaemia of chronic disease?
- Iron dysregulation: iron not released for use in bone marrow
- The marrow shows a lack of response to erythropoietin
- Reduced lifespan of red cells.
What can cause reduced erythropoiesis?
- Empty bone marrow - unable to respond to stimulus from EPO e.g. after chemotherayp or toxic insult such as parvovirus or in aplastic anaemia.
- Marrow infiltrated by cancer cells or fibrous tissue (myelofibrosis) means the normal haemopoietic cells are reduced.
When is anaemia of chromic disease seen?
Renal disease, RA, SLE (lupus), IBD (Ulcerative colitis or crohn’s), Chronic infections.
What is a functional iron deficiency?
Sufficient iron in the body but not available to the developing erythrocytes cells.
What happens to iron?
Macrophages ‘eat’ old senescent RBCs and recycle iron.
Iron recycling is the main source of iron for new RBCs
Small amount of iron is absorbed from gut.
BUT, erythrocyte islands with ‘nursing’ macrophages. (Iron gets stuck in macrophages.
Why does iron get stuck in macrophages?
Hepcidin - Inhibit movement of iron from cells into blood by inhibiting ferroportin.
Hepcidin is produced by the liver and this degrades ferroportin so that iron can get in but not out of cells.
This means than iron cannot be released from macrophages or expected out into the blood.
Ferroportin diegredation also prevents iron absorbtion from the gut.
How is hepcidin regulated?
- By inflammatory cytokines.
- Transferrin receptor
- HFE (human haemochromatosis protein)
How does inflammation lead to anaemia?
Produce more cytokines (IL-6) so, this increases the amount of hepcidin produced which keeps iron in cells.
Degrades ferroportin.
Decreased iron released from RES and decreased absorbtion from the gut.
Inhibition of erythropoiesis in bone marrow.
(Cytokines also inhibit the kidney from responding to EPO).
Cytokines also effect RBCs produced so reduced lifecycle. So, anaemia.
Anaemia of chronic renal failure?
Reduced erythropoietin reduction due to damage to kidneys
Often associated with raised cytokines
Reduced clearance of hepcidin
Increased hepcidin production due to inflammatory cytokines.
Dialysis damage due to RBCs and loss due to bleeding.
Reduced lifespan of RBCs as a direct effect of uraemia - Also inhibit megakaryocytes leading to low platelet count.
What investigations would be done on people with chronic renal failure?
Ferritin is the best test of what iron stores are doing.
It is produced by the liver and is an inflammatory protein so, may not be the most accurate in chronic disease.
Now use CHr - if this is low there is not enough iron stores.
Elevated CRP as chronic disease / Inflammation.
Also often have normocytic normochromic or microcytic anaemia.
Treatment of anemia of chronic disease?
Treat the underlying condition
If associated renal failure - recombinant human erythropoietin (must have all bulding blocks e.g. Iron and Vit B12 / folate
Ensure Vit B12 folate and iron stores are adequate.
Transfuse - if all else fails and patient is symptomatic.
Management of anaemia of chromic renal failure?
Use reticulocyte Hb content (CHr) to assess functional iron deficiency.
Give iron if ferritin under 200um/L or CHr low then give Iron.
Iron given as IV as absorbtion is impaired (…Hepcidin)
Haematological changes in Renal disease?
Low Hb:
- ARF / ACD
- Blood loss
- Haematinic causes
High Hb:
- Post renal transplant
- Renal tumour
Low WBCs:
- Immunosuppression pops renal transplant drugs
- Marrow infiltration eg in myeloma
High WBCs:
- Inflammation
- Connective tissue disease
- Infection
- Drugs: steroids
Low platelet:
- Direct effect of uremia on platelet production
- Drugs
- haemolytic uraemic syndrome
High platelet:
- Reactive
- Bleeding
- Iron deficiency
What is rheumatoid arthritis and how is it treated?
Chronic inflammation of the joints.
Treated with:
- Analgesics often NSAIDs
- Corticosteroids
- Chemotherapy eg methotrexate
- Biological agents
What chages occur in the blood count of rheumatoid arthritis?
Low Hb:
- ACD
- Blood loss
- Haematinic Immune
High WBCs:
- Associated inflammation
- Infection
- Drug reactions (steroids as more susceptible to infections)
Low WBCs:
- Drugs (methotrexate and no folic acid)
- Immune
High platelets:
- Reactive
- Bleeding
- Iron deficiency
Low
- Drug autoimmune splenomegaly (Felty’s)
What is felty’s syndrome? What is Neutropenia?
A triad of splenomegaly, Rheumatoid Arthrits and Neutropenia
Neutropenia:
- Secondary to spenomegaly, peripheral destruction of neutrophils, and failure of bone marrow to produce neutrophils.
- Higher level of G-CSF that you’d expect for neutrophil level, insensitivity of myeloid cells to cytokines.
Chronic liver cirrhosis?
Portal hypertension (Increase in resistance to blood coming from spleen and gut) - This causes spenomegaly which leads to:
- Splenic sequestration of cells
- Overactive removal of cells.
Haematological features of liver disease?
Esophageal varices as a consequence of portal hypertension.
More susceptible to bleeding as not enough clotting factors
Blood loss is cause of anaemia as less clotting factors.
- Deficiency of coagulation factors
- Endothelial dysfunction
- Thrombocytopenia
- Defective platelet function.
May become iron deficient due to chronic blood loss.
What is zieve’s syndrome?
Acute haemolytic anaemia due to changes in cell membrane.
These changes alter the shape of the cells so they are more prone to being damaged as they circulate.
Lipid abnormalities affecr RBC membrane leading to macrocytosis, targt cells and can lead to haemolysis.
Thrombocytopenia in liver disease?
Thrombocytopenia in 75% patients with liver disease
Impaired production as thrombopoietin is made in the liver
Splenic pooling
Increased destruction
Functional problems - platelets don’t work properly.
Other haematological features of liver disease?
Alcohol excess
- Directly toxic to bone marrow cells
- Secondary malnutrition because of folic acid deficiency
Hepatitis
- Bone marrow failure can develop after an episode of hepatitis
Immune
- Immune mediated anaemia, thrombocytopenia or neutropenia
Haematological features of liver disease?
Low Hb:
- Impaired production (iron or folate deficiency, alcohol toxicity)
- Splenic pooling
- Increased destruction (bleeding / haemolysis..)
High Hb:
- Alcohol
Low WBCs:
- Impaired production
- Splenic pooling
- Increased destruction
High WBCs:
- Steroids
Low platelets:
- Impaired pruduction
- Splenic pooling
- Increased destruction
High platelets:
- Bleeding
Post operative reactive haematological changes?
Always compare to before to comfirm deficiencies are due to operation.
Low Hb:
- Bleeding
High Hb:
- Dehydration
Low WBCs:
- Severe sepsis
High WBCs:
- Infection / Sepsis
Low Platelet:
- Medication (heparin / antibiotics),
- Sepsis
High platelet:
- Bleeding,
- Infection,
- ‘Reactive’
Haematological changes with infection?
- Chronic infection can cause anaemia of chronic disease / inflammation.
- Infection with malaria can cause haemolysis.
- Bacterial infection is often associated with a neutrophilia
- Severe infection / sepsis can cause a neutropenia
- Parasitic infections are assiciated with an eosinophilia
- Viral infections can cause a lymphocytosis
- Infections can cause a reactive thrombocytosis
- Severe infection can cause thrombocytopenia
- Thrombocytopenia may be associated with DIC in severe sepsis.
What is DIC?
Disseminated intravascular coagulation
- Pathologial activation of coagulation
- Numerous microthrombi are formed in the circulation
- This leads to consumption of clotting factors and platelets and a haemolytic anaemia
- Clotting tests are affected - usually raised PT/INR, raised APTT, low fibrinogen and raised D dimers / fibrin degredation products.
- Risk of bleeding and thrombosis
Haematological changes in cancer?
Low Hb:
- Bleeding e.g. Bowel cancer
- Iron deficiency
- ACD
- Chemotherapy
High Hb:
- EPO secreting
- Tumours
Low WBCs:
- Chemotherapy
- Sepsis
- Bone Marrow
- Infiltration
High WBCs:
- Infection
- Inflammation
Low platelet:
- Chemotherapy
- Sepsis
- Bone marrow infiltration
- DIC
High platelet:
- Infection
- Inflammation
- Bleeding
- Iron deficiency
What is a leucoerythroblastic film?
Granulocyte precursors and nucleated RBCs on a blood film.
- Sepsis / shock
- Bone marrow infultration by carcinoma or haematological malignancy
- Severe megaloblastic anaemia
- Primary myelofibrosis
- AML / MDS
- Storage disease
When does a leukoerthroblstic film occur?
- Sepsis / Shock
- Bone marrow infiltration by carcinoma or haematological malignancy
- Severe megoloblastic anaemia
- Primary myelofibrosis
- AML/ MDS
- Storage disease
