Haem: Haematology of Systemic Disease (Laz) Flashcards
What are the principles of haematological disorders
Either excess or deficiency of:
-** Soluble proteins **
- Factor VII excess —-> Haemophilia A
- Protein C excess —>Pro-thombotic disease
**- Cellular Components **
- Erythrocytes —> polycythaemia v anaemia
- Leucocytes —> leukaemia
- Lymphocytes -> leukaemia v lymphopenia
- Platelets ——-> essential thrombocytopenia or ITP
Additionally: autoimmune disorders
Differentiate between Primary and Secondary haematological disorders
Primary: inherited or acquired (e.g. Haemophilia, Sickle cell, Polycythaemia Vera)
**Secondary: ** normal haematological system responding to environmental changes or other non-haem pathology (e.g. inflammation driven Factor VIII excess, high altitude polycythaemia)
List some ways in which lymphoma can cause jaundice.
- Direct liver involvement
- Compression of the bile duct
- Causing autoimmune haemolytic anaemia
Which types of cancer are associated with causing secondary polycythaemia?
- Renal cell carcinoma
- Liver cancer
- Due to the production of EPO
Which types of anaemia can be a first presentation of cancer and are caused by cancer?
- Iron deficiency
- Anaemia of chronic disease
- Haemolytic anaemia
- Leucoerythroblastic anaemia
What is the most common cause of iron deficiency anaemia?
Occult blood loss (e.g. GI cancers, urinary tract cancers)
*Iron deficiency anaemia is bleeding until proven otherwise! *
What are the typical laboratory findings of iron deficiency anaemia?
- Microcytic hypochromic anaemia
- Low ferritin
- Low transferrin saturation
- High TIBC
What is leucoerythroblastic anaemia?
Anaemia characterised by the presence of red and white cell precursors released form bone marrow.
As premature RBCs are less functional = anaemia
What are the morphological features of leucoerythroblastic anaemia seen on blood film?
- Tear drop red blood cells (aniso- and poikilocytosis)
- Nucleated RBCs (=premature RBCs)
- Immature myeloid cells
What does leucoerythroblastic anaemia tend to be caused by?
- First manifestation of **bone marrow infiltration commonly caused by malignancy or mets ** (leukaemia, lymphoma, myeloma, solid tumours)
- Myelofibrosis
- Severe infection (e.g. miliary TB, fungal infection)
Define haemolytic anaemia.
Anaemia caused by reduced red blood cell survival
List some key laboratory findings in haemolytic anaemia.
- Anaemia
- Raised reticulocytes (not nucleated as seen in leucoerythroblastic anaemia)
- Raised unconjugated bilirubin - prehepatic
- Raised LDH (intracellular enzyme)
- Low haptoglobins (important for binding to free Hb, due to high levels of haemolysis the levels of haptoglobins decrease as its all binding to a lot of free Hb)
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?
Spherocytes
Agglutinatinon
(alongside DAT +ve) = AIHA
Outline the differences between the 2 types of AIHA
List some systemic diseases that can cause autoimmune haemolytic anaemia.
- Cancer involving the immune system (e.g. lymphoma)
- Disease of the immune system (e.g. SLE)
- Infections (disturbs the immune system)
Lab results for Non-immune mediated anaemia
DAT -ve
RBC fragments (schistocytes)
Thrombocytopenia
Hereditary spherocytosis
List some causes of non-immune haemolytic anaemia.
- Infection (e.g. malaria - parasite enters RBC causing it to die)
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia (MAHA)
2 Main causes of Micro-Angiopathic Haemolytic Anaemia (MAHA).
- Adenocarcinoma
- DIC, Red cell fragmentation, Low platelets - Haemolytic Uraemic Syndrome
- Triad: MAHA + AKI + thrombocytopenia
- Caused by e.coli toxin O157
Outline the how adenocarcinomas can result in MAHA.
- 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
NOTE: always consider underlying adenocarcinoma in any patient presenting with MAHA
List some causes of secondary polycythaemia.
- Cancer (renal, hepatocellular, bronchial)
- High altitude
- Hypoxic lung disease
- Congenital cyanotic heart disease
How would you interpret an abnormal WBC count
- Look at the FBC - any changes in Hb, Platelets as well? Any changes in lineages in WBC (myeloid e.g. neutrophils) v lymphocytes)
- Look at blood film - normal or abnormal morphology (chronic vs acute leukaemia)
What is the main difference seen in the blood film of patients with acute and chronic leukaemia?
- Chronic - mature white cells are raised
- Acute - immature blast cells are raised
List the 2 main causes of neutrophilia.
Reactant Neutrophilia
- Infection (most likely pyogenic infection)
- Corticosteroids
- Underlying neoplasia
- Tissue inflammation (e.g. colitis, pancreatitis)
Malignant
- Myeloproliferative
- Leukaemic disorders
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
What are some key blood film features suggestive of AML vs CML?
AML
* Neutropenia
* Myeloblasts
CML
* Neutrophilia/basophilia
* Splenomegaly
List some 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)
Which gene mutation causes chronic eosinophilic leukaemia?
FIP1L1-PDGFRa fusion gene
Which type of virus typically causes basophilia?
Pox viruses
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 lymphocytes (more abundant cytoplasm - lower N:C ratio) or atypical lymphocytes (EBV)
- CLL or NHL: small lymphocytes (large N:C ratio) and smear cells
Outline how flow cytometry is used to identify cell types.
- Fluorescently labelled monoclonal antibodies targeted at different antigens are washed over the cells
- Cells are passed through the flow cytometer and the fluorescence is recorded
- Dependent on the antigens present on the cells, you can identify the stage of maturation
What are the CD markers that differentiate between B and T Cells
B cells —> CD19, CD22
T cells —> CD2
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 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)
Causes of Lymphopenia
- HIV
- Autoimmune disorders
- Inherited immune deficiency syndromes
- Drugs (chemotherapy)
Female aged 39 treated for breast cancer 4 years previously presents with recent onset jaundice and hepatomegaly. The following are her blood results:
Hb - 87g/l
Reticulocyte 15x10^9 (20-92)
Bilirubin 50mm/L
DAT -ve
Blood film in picture
What is the diagnosis:
A) Iron deficiency anaemia
B) Anaemia of chronic disease
C) BM mets from breast cancer
D) MAHA
E) AIHA
B) BM mets from breast cancer (accounts for low reticulocyte count - as BM is infiltrated, nucleated RBCs seen in film)
- Not IDA as would not expect jaundice, would not give nucleated red blood cells in PB
- Not MAHA as would not get leucoerythroblastic problems in blood as BM is healthy
- Not AIHA as DAT is -ve
