Interactive Haematology Flashcards
Describe where you would see … myeloblasts
<5%
5-20%
>20%
<5%: Normal BM
5-20%: Myelodysplasia
>20%: Acute Myeloid Leukaemia (AML)
Where should myeloblasts never be seen?
Peripheral blood
Presence indicates AML or leucoerythroblastic picture
Which cells may contain Auer rods ?
Myeloblasts (though not all)
Describe where you would see … lymphoblasts
<5%
>20%
<5%: Normal BM
>20%: Acute Lymphoblastic Leukaemia
Give 2 causes of an MCV of 50-70
IDA
Thalassaemia
Give 3 causes of an MCV of 100-108
Hypothyroidism
Alcoholism
Combined Iron + Folate deficiency
Give 2 causes of an MCV of 115-125
B12 deficiency
Folate deficiency
Name 2 B cell markers and what they are epitopes for
CD19: CAR T cells
CD20: Rituximab MOAB
Name 4 T cell markers
CD3 (Mature)
CD4 (Helper)
CD8 (Cytotoxic)
CD5
Name a marker of lymphoid differentiation
TdT: marker of immature T + B lymphoblasts
Name a marker of mature B cells and plasma cells
Surface Immunoglobulini
Give 2 causes of raised globulins
Monoclonal rise due to lymphoid malignancy: Myeloma
Polyclonal rise as part of reactive response: Infection, SLE, untreated HIV
How does myeloma cause a rise in immunoglobulins?
Excess of clonal plasma cells
Plasma cells secrete immunoglobulins
Immune paresis: e.g. in IgG myeloma, massively raised IgG, so remaining IgA + IgM are suppressed
What patterns of abnormalities should you look for when interpreting bloods?
Isolated single lineage cytopenia (all other values normal)
Pancytopenia
Isolated single lineage raised (all other values normal)
Isolated single lineage raised (other values suppressed)
How should you look at blood values?
- As a “group”:
Hb + MCV
WBC + differential
Platelets - Pattern
- Morphology
Name 2 conditions in which spherocytes may be seen
AIHA
Hereditary spherocytosis
What test determines whether spherocytosis is inherited or acquired?
DAT
List 4 causes of hereditary haemolytic anaemia
Hereditary spherocytosis
G6PD deficiency
Sickle cell (structural Hb pathy)
Thaalassaemia major (globin chain imbalance)
Name 2 types of acquired immune haemolytic anaemia
Autoimmune: linked to other immune disease
Alloimmune: post-blood transfusion
Name 4 causes of acquired non-immune haemolytic anaemia
Malaria
Drugs
Oxidant drugs
Snake venom
List 4 features of haemolytic anaemia regardless of aetiology
Unconjugated hyperbilirubinaemia
Reticulocytosis
Raised LDH
Lowered haptoglobins (bind to free Hb, thus are consumed)
What distinguishes anaemia of chronic disease from iron deficiency?
L Fe: confirms Fe deficiency
N/ H Fe: can be ACD (or Fe deficiency with inflammation)
L/N Transferrin/ TIBC: ACD
H Transferrin/ TIBC: Fe deficiency
What is ACD?
Anaemia of inflammation, mediated by high hepcidin levels
Body stores Fe adequate but sequestered + unavailable for erythropoeisis
How are iron stores sequestered in ACD?
Hepcidin is master regulator of Fe
Elevated hepcidin inhibits GI absorption of Fe + sequesters Fe in macrophage + kupffer cells
Why are iron stores sequestered in inflammation?
Hepcidin is an antibacterial/ inflammatory response protein
Removing available Fe from blood circulation deprives invading bacteria of Fe required for rapid proliferation
What can cause an isolated single lineage cytopenia with otherwise normal FBC?
Often peripheral destruction/ shortened survival
Less often failure of production
What can cause peripheral destruction/ shortened survival resulting in isolated cytopenia?
Immune destruction
Non immune: Infections (malaria), mechanical (DIC), consumption sequestration (splenomegaly)
What can cause failure of production resulting in isolated cytopenia?
Haematinics: Fe deficiency
Drugs causing isolated agranulocytosis
What kind of cytopenia is caused by B12/ folate deficiency?
Pancytopenia
B12/ folate required for DNA synthesis
Failure in all 3 lineages coming out of BM
More marked in erythroid as more rapid turnover
What cytopenia is generally seen with bone marrow disorders?
Pancytopenia
Suppression of all lineages
Give 2 non malignant causes of pancytopenia
DNA synthesis failure (B12/ folate deficiency)
Aplastic anaemia (Chemo drugs, Idiosyncratic post hep C)
Give 2 malignant causes of pancytopenia
Metastatic non-haematological cancer that has spread to the bone marrow
Haematological cancer infiltrating BM: Acute leukaemia, myelodysplasia, myeloma, lymphoma
Name 5 cancers that metastasise to the bone
Breast
Prostate
Lung
Thyroid
Kidney
What distinguishes non malignant from malignant causes of pancytopenia?
Malignant has leucoerythroblastic picture
What is the sigle most useful test to confirm the likely haematological diagnosis?
BCR ABL 1 RT-PCR assay
for chronic myeloid leukaemia
Blood film: excess white cells, heterogenous, mainly myeloid
What is the likely cause of massive splenomegaly +/- hepatomegaly?
Chronic myeloid leukaemia
What is the likely cause of hepatosplenomegaly and lymphadenopathy?
Lymhoid disorders
How can CML be monitored during treatment?
RT-PCR for % of cells with BCR-ABL fusion protein to get ratio of malignant: normal
What is the most useful haematological test? What is the diagnosis?
Immunophenotyping for CD19/CD5/CD3
CLL
Blood film: mature normal lymphocytes, lots of smudges/ smear cells (rupture of fragile lymphocytes)
Describe the normal expression of CD5 and CD19 in lymphocytes
T: CD5 +ve, CD19 -ve
B: CD19 +ve, CD5 -ve
What is the worst cell based prognostic factor in CLL?
Chr 17p deletion +/- TP53 point mutation
What are the clinical issues of CLL?
Increased risk of infection: non functional mature B cells + hypogammaglobulinaemia
BM failure: malignant cell proliferation
Lymphadenopathy +/- splenomegaly: spread
Transformation to high grade lymphoma
AI complications e.g. AIHA
Name 3 tyrosine kinase inhibitors
Imatinib: ABL TK inhibitor
Ruxolotinib: JAK2 TK inhibitor
Ibrutinib: Bruton TK inhibitor
What tyrosine kinase inhibitor can be used in the targeted treatment of CLL?
Ibrutinib
Deprive B cells of bruton TK to recreate phenotype of lacking B cells which is seen in Bruton’s X-linked agammaglobulinaemia
Give 3 treatment options in CLL
BCR kinase inhibitors e.g. Ibrutinib
BCL2 inhibitors e.g. Venetoclax
Chimaeric Antigen Receptor T cells (CAR-T)
What is the most common cause of renal failure in multiple myeloma?
Cast nephropathy
High serum free light chain levels
Can pass through BM in kidneys + precipitate in tubules
