Haematology In Systemic Disease Flashcards
What is anaemia of chronic disease/inflamamtion
Dyserythropoiesis
1. Iron dysregulation: iron not released for use in bone marrow
2. the marrow shows a lack of response to erythropoietin
3. reduced lifespan of red cells
Renal disease, inflammatory conditions such as Rheumatoid arthritis, SLE, Inflammatory bowel disease (Ulcerative Colitis or Crohn’s), chronic infections etc.
What is functional iron deficiency
Sufficient iron in the body but not available to the
developing erythroid cells
Plenty of iron in the macrophages but they cant give it to the red cells that need it
What is the main source of iron for new rbcs?
Macrophages ‘eat’ old senescent RBCs and recycle iron
Iron recycling is the main source of iron for new rbc
Small amount of iron absorbed from gut
What is hepcidin regulated by?
Regulated by:
HFE
Transferrin receptor
Inflammatory cytokines
What is the role of hepcidin
Degrades ferroportin a protein involved in moving iron out of cells - prevents iron release from macrophages and prevents iron absorption from gut
What do inflammatory cytokines do in anaemia of chronic disease ?
Iron dysregulation: iron not released for use in bone marrow
Due to inflammatory cytokines
the marrow shows a lack of response to erythropoietin
Due to inflammatory cytokines
reduced lifespan of red cells
Due to inflammatory cytokines
What is anaemia of chronic renal failure?
Reduced erythropoietin production due to damage to kidneys
Often associated with raised cytokines
Reduced clearance of hepcidin
Increased hepcidin production due to inflammatory cytokines
Dialysis-damage to rbc and loss due to bleeding
Reduced lifespan of RBC as a direct effect of uraemia - Also inhibits megakaryocytes leading to low platelet counts
What are investigations into acd?
Often normocytic normochromic or microcytic anaemia
Normal or high ferritin
Normal or high Reticulocyte Haemoglobin content (CHr)
CRP often elevated
In most ppl, ferritin is best test of iron stores - ferritin produced by liver -
in some patients ferritin levels high (liver disease) - liver pushing it out - in these patients it is not. A good measure -
chr low is iron deficient . Chr will be normal/high if enough /a lot of iron stores -
You may read about: Low serum iron and normal/high % transferrrin saturation Not very reliable
What is the treatment for ACD?
Treat the underlying condition
If associated renal failure
Recombinant human Erythropoietin
Must have all building 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 - transfuse sparingly and only i patient is clinically symptomatic
What is the management of anaemia of chronic renal failure
Use Reticulocyte Haemoglobin Content (CHr) (or % hypochromic cells) to assess for functional iron deficiency - Iron given intravenously for patients with anaemia of renal failure
Give iron if ferritin <200 mg/L (normal range 15-400mg/L ) or CHr low then give iron
Iron given as IV as absorption is impaired (….Hepcidin)
What are abnormalities in RBCs in renal disease?
Low • ARF/ACD • Blood loss • Haematinic causes
High • Post renal transplant • Renal tumour
What are abnormalities in WBCs in renal disease?
Low: • immunosuppression
post renal transplant
drugs; • marrow infiltration eg in
myeloma
High • inflammation • connective tissue
disease • Infection • drugs: steroids - Steroids to damp down immune cause of renal failure
What are abnormalities in platelets in renal disease?
Low • direct effect of uraemia on platelet production • drugs • Haemolytic uraemic syndrome
High • reactive • bleeding • iron deficiency
How is rheumatoid arthritis treated
Chronic immune mediated inflammatory condition Treated with ◦ analgesis often NSAIDs ◦ Corticosteroids ◦ chemotherapy eg methotrexate ◦ biological agents
What are abnormalities in RBCs in rheumatoid arthritis?
Low • ACD • blood loss eg
due to NSAIDs/corticost eroids • Haematinic • Immune
What are abnormalities in WBCs in rheumatoid arthritis?
High •Associated inflammation •infection •drug reactions…..
Low •drugs eg methotrexate •immune
What are abnormalities with platelets in rheumatoid arthritis?
High •reactive •bleeding •iron deficiency
Low •drugs autoimmune splenomegaly (Felty’s)……
What is feltys syndrome
Triad of RA, splenomegaly, neutropenia
Neutropenia
◦ secondary to splenomegaly, peripheral destruction of neutrophils, and failure of bone marrow to produce neutrophils
◦ high level of G-CSF, insensitivity of myeloid cells to cytokines ◦
What does portal hypertension cause?
Portal Hypertension causesvsplenomegaly which leads to:
• Splenic sequestration of cells • Overactive removal of cells
What are haematological features of liver disease?
Blood loss
Response to anaemia may be impaired due to the development of iron deficiency
deficiencies of coagulation factors
endothelial dysfunction
thrombocytopenia
defective platelet function
Portal hypertension Increased back up of blood - veins swell
clotting factors made in the liver
thrombocytopenia maybe due to splaenomaegly
defective platelet function - other chemical changes
prone to bleeding
chronic blood loss - may become iron deficien
FACT: Many clotting factors are made by the liver
Response to anaemia may be impaired due to the development of iron deficiency
What is zieves syndrome?
Zieve’s syndrome- acute haemolytic anaemia
Lipid abnormalities affect RBC membrane leading to macrocytosis, target cells and can lead to haemolysis
Describr 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
Liver disease bc of immune causes eg primary biliary cirrhosis
What are some haematological features of liver disease?
Alcohol excess
◦ Directly toxic to bone marrow cells
◦ Secondary malnutrition (folic acid deficiency)
Hepatitis
◦ Bone marrow failure can develop after an episode of hepatitis
Immune
◦ Immune mediated anaemia, thrombocytopenia or neutropenia
Describe th eRBC count in liver disease
Low • Impaired production (iron or folate deficiency, alcohol toxicity) • Splenic pooling • Increased destruction (bleeding/haemolysis etc)
High • alcohol
Describe the wbc count in liver disease
Low • Impaired production • Splenic pooling • Increased destruction
High • Steroids
Describe the platelet count in liver disease
Low • Impaired production • Splenic pooling • Increased destruction
High • Bleeding
What are the post operative reactive changes to rbcs?
Low • Bleeding
High • Dehydration
What are the post operative reactive changes to wbc count
Low • Severe sepsis
High • Infection/Sepsi s
What are the post operative reactive changes to platelet count
Low •Medication (heparin/antibiotics) •Spesis +/- DIC
High •Bleeding •Infection •‘reactive’
What are the changes to rbcs with infection
Chronic infection can cause anaemia of chronic disease/inflammation Infection with malaria causes haemolysis
What are the changes to WBCs with infection
Bacterial infection is often associated with a neutrophilia
Severe infection/sepsis can cause a neutropenia
Parasitic infections are associated with an eosinophilia
Viral infections can cause a lymphocytosis
What are the changes too platelets with infection
Infection can cause a reactive thrombocytosis
Severe infection can cause thrombocytopenia Thrombocytopenia may be associates with DIC in severe sepsis
How can sepsis lead to clotting abnormalities
Disseminated intravascular coagulation
Pathological 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 degradation products
Risk of bleeding and thrombosis
What are changes to rbcs with cancer?
Low
• Bleeding eg Ca bowel
• Iron deficiency • ACD
• Chemotherapy
High
• EPO secreting
tumours
What are Changes to WBCs with cancer
Low • Chemotherapy • Sepsis • Bone marrow
infiltration
High • Infection • Inflammation
What are changes to platelets with cancer
Low • Chemotherapy • Sepsis • Bone marrow infiltration • DIC
High • Infection • Inflammation • Bleeding • Iron deficiency
What is a leucoerythroblastic film
Granulocyte precursors and nucleated RBC on blood film Sepsis/shock Bone marrow infiltration by carcinoma or haematological malignancy Severe megaloblastic anaemia Primary Myelofibrosis AML/MDS Storage diseases
