Haem 5: Haem of systemic disease Flashcards
Which types of anaemia can be caused by cancer?
Iron deficiency
Anaemia of chronic disease
Haemolytic anaemia
Leucoerythroblastic anaemia
Which types of cancer are associated with causing secondary polycythaemia? Why?
Renal cell carcinoma
Liver cancer
Due to the production of EPO
What do these laboratory findings suggest?
Ferritin: Low
Transferrin saturation: Low
TIBC: High
What is the most common cause of this condition?
Iron deficiency anaemia
Occult blood loss (e.g. GI cancers, urinary tract cancers)
What is leucoerythroblastic anaemia? Cause?
Anaemia characterised by the presence of red and white cell precursors
Infection: miliary TB/severe fungal infection
Malignancy: myelofibrosis/ leukaemia/lymphoma/myeloma/ metastatic Ca
USUALLY A MALIGNANCY INVOLVING BM
Morphological features on blood film of leucoerythroblastic anaemia?
- Tear drop red blood cells (aniso- and poikilocytosis)
- Nucleated RBCs
- Immature myeloid cells
Define haemolytic anaemia?
Anaemia caused by reduced red blood cell survival
List some key laboratory findings in haemolytic anaemia.
Anaemia Raised LDH Raised reticulocytes Raised unconjugated bilirubin Low haptoglobins NOTE: LDH is an intracellular enzyme that is released when RBCs are destroyed
What are the two main groups of haemolytic anaemia? List some examples.
Inherited (defects with the cell)
- Hereditary spherocytosis (membrane problem)
- G6PD deficiency (enzyme problem)
- Sickle cell disease, thalassemia (haemoglobin problem)
Acquired (defects with the environment)
- Immune-mediated
- Non-immune mediated
Which test distinguishes immune-mediated and non-immune mediated haemolytic anaemia?
DAT or Coombs’ test
DAT +ve means that the haemolytic anaemia is mediated through immune destruction of red cells
What morphological change is seen on the blood film of patients with autoimmune haemolytic anaemia?
What are some systemic diseases that can cause this?
Cancer involving the immune system (e.g. lymphoma)
Disease of the immune system (e.g. SLE)
Infections (disturbs the immune system)
List some causes of non-immune haemolytic anaemia.
Infection (e.g. malaria)
Microangiopathic haemolytic anaemia (MAHA)
List some key features of MAHA. What is it usually caused by?
Usually caused by underlying adenocarcinoma
DIC/bleeding
Red cell fragments
Low platelets
MoA of MAHA?
Another cause?
An underlying adenocarcinoma produces procoagulant cytokines that activate the coagulation cascade
This leads to DIC and the formation of fibrin strands in various parts of the microvasculature
Red cells will be pushed through these fibrin strands and fragment
Another cause is HUS (instead of adenocarcinoma driven)
What should always be considered in any patient presenting with MAHA
underlying adenocarcinoma
List some causes of secondary polycythaemia.
Cancer (renal, hepatocellular, bronchial)
High altitude
Hypoxic lung disease
Congenital cyanotic heart disease
What disease is characterised by primary raised erythrocytes?
Polycythaemia vera
What is the main difference seen in the blood film of patients with acute and chronic leukaemia?
Acute – immature blast cells are raised
Chronic – mature white cells are raised
List some causes of neutrophilia.
med?
Corticosteroids (due to demargination)
Underlying neoplasia
Myeloproliferative/leukaemia disorder
Tissue inflammation (e.g. colitis, pancreatitis)
Infection
List some infections that characteristically do not cause neutrophilia.
Brucella
Typhoid
Many viral diseases
List some key features of a reactive neutrophilia on a blood film.
Band cells (presence of immature neutrophils (band cells) show that the bone marrow has been signalled to release more WBCs)
Toxic granulation
Clinical signs of infection/inflammation
What are some key blood film and clinical features suggestive of a myeloproliferative disorder?
Neutrophilia
Basophilia
Immature myelocytes
Splenomegaly
NOTE: you may see raised Hb and raised platelets in CML if it affects those lineages
Key blood film features suggestive of AML?
Neutrophilia
Myeloblasts
Causes of monocytosis?
Bacteria - TB, Brucella, Typhoid
Viral - CMV, VZV
Sarcoidosis
Chronic myelomonocytic leukaemia
List some causes of reactive eosinophilia.
Parasitic infection
Allergy (e.g. asthma, rheumatoid arthritis)
Underlying neoplasms (e.g. Hodgkin’s lymphoma, T cell lymphoma, NHL)
Drug reaction (e.g. erythema multiforme)
What does FIP1L1-PDGFRa fusion gene normally cause?
chronic eosinophilic leukaemia
Which type of virus typically causes basophilia?
Pox viruses
Which disease is caused by a genetic deficiency of factor IX?
Haemophilia B
Which disease is caused by a genetic excess of factor IX?
Factor IX Padua
How can haemophilia B be treated using gene therapy?
Factor IX Padua gene can be put into adenoviruses as a vector, to cause factor IX production
Which disease is caused by an acquired mutation in JAK2?
Polycythaemia vera
Which disease is caused by an acquired mutation in PIG A?
PNH paroxysmal nocturnal haemoglobinuria
What is a raised factor VIII likely to be secondary to?
Inflammatory process
What type of anaemia is caused by mycoplasma infection?
Immune haemolytic anaemia
How do you distinguish a reactive neutrophilia vs a malignant one?
Reactive neutrophilia has a limit (they won’t be sky high)
No immature cells in reactive neutrophilia
Malignant has immature cells + either basophils (indicative of CML) or myeloblasts (indicative of AML)
What is the most common cause of a reactive lymphopaenia?
HIV
In which 2 conditions might smear cells appear on the blood film?
CLL
Non-hodgkins lymphoma
What investigations are typically used when investigating lymphocytosis?
Clinical examination
FBC
Light microscopy
Flow cytometry (identify lineage and stage of differentiation)
Molecular genetics (TCR or Ig gene)
List some causes of reactive lymphocytosis.
Infection (EBV, CMV, toxoplasmosis, rubella, HSV)
Autoimmune diseases
(NOTE: these are more likely to cause lymphopaenia)
Sarcoidosis
How would the lymphocytes seen on a blood film due to a viral infection be different from leukaemia/lymphoma?
Viral infection: reactive or atypical lymphocytes (EBV)
CLL or NHL: small lymphocytes and smear cells
What is light chain restriction?
An individual B cell will either express kappa or lambda light chains (not both)
In response to an infection, you will get a polyclonal B cell response so there will be a roughly even mixture of kappa and lambda light chains
In lymphoproliferative disorders, monoclonal proliferation of a B cell expressing only one type of light chain (e.g. kappa) will mean that the proportion of kappa relative to lambda will increase (e.g. showing an overwhelming majority of kappa)
How is B cell clonality determined?
Look for light chain restriction - the ratio of kappa and lambda
(60:40 would be reactive, 99:1 would be malignant)
Recall 2 tests that can determine immunophenotype in blood malignancies, and one use of knowing this info?
Flow cytometry
Immunohistology
Use: working out if T or B lineage, working out if myeloid or lymphoid
Recall 2 tests that can determine cytogenetics in blood malignancies and one use of knowing this info?
Translocations
FISH studies
Use: Philadelphia chromosome identification
Recall 2 tests that can determine molecular genetics in blood malignancies and one use of knowing this info?
PCR
Pyro sequencing
Use: Detect JAK2 mutation, or BCR ABL cDNA
