Haem 2 - Haematology in systemic disease and intro to haemopathology

Question 1

Which type of leukocytes are in excess in

CML
CLL

Answer 1

CML - granulocytes (e.g. eosinophils, basophils, neutrophils) (granulocytes come form myeloblasts)

CLL - lymphocytes

Question 2

Iron deficiency anaemia lab findings

o  ferritin
o  transferrin saturation
o TIBC/Transferrin

Blood film

Answer 2

o Decreased ferritin
o Decreased transferrin saturation
o Increased TIBC/Transferrin

o Microcytic hypochromic anaemia

Question 3

What is leucoerythroblastic anaemia?

What will you see on the blood film

Causes

Answer 3

• Usually the first manifestation of BM malignancy
• Anaemia with immature BM cells in the peripheral blood

• Peripheral blood film
o Teardrop RBC – anisocytosis, poikilocytosis
o Nucleated RBCs (normal in BM)
http://www.medical-labs.net/wp-content/uploads/2014/03/Nucleated-red-blood-cell-Normoblast.jpg
o Immature myeloid cells (R cell - myelocyte) (normal in BM)
https://imagebank.hematology.org/getimagebyid/60507?size=3

• Leucoerythroblastic film can suggest BM infiltration
• Causes of leucoerythroblastic film
o Malignant - haematopoietic, non-haematopoietic (metastatic)
o Severe infection - military TB, severe fungal infection
o Myelofibrosis

low reticulocyte count

Question 4

Haemolytic anaemia lab findings

Answer 4

o	Anaemia – may be compensated
o	Reticulocytotis
o	Increased unconjugated bilirubin (pre-hepatic)
o	Increased LDH
o	Decreased Haptoglobins

Question 5

Which 2 conditions present with spherocytes on blood film and how would you differentiate

Answer 5

Hereditary spherocytosis
AIHA

Dat/ Coomb’s test positive in AIHA

Question 6

What is AIHA associated with + how to differentiate cause

Answer 6

•	Associated with systemic diseases involving immune system
o	Malignancy e.g. Lymphoma, CLL
o	Auto-immune e.g. SLE
o	Infection e.g. mycoplasma 
o	Idiopathic

• Agglutination
• Warm agglutination (80-90%) – IgG antibodies (>37), extravascular haemolysis
o Idiopathic
o SLE
o CLL
o Lymphoma
o Drug allergies – penicillin, cephalosporin, sulfa-drugs, methyldopa
o Mx: steroids, splenectomy, immunosuppression

• Cold agglutination (10-15%) – IgM (<37), intravascular haemolysis
o Idiopathic
o M. pneumoniae
o Mononucleosis/EBV
o CMV
o Mx: treat underlying condition, avoid cold, chlorambucil (chemo)

• In cold temperatures, IgM antibodies react with RBC antibodies + cause them to agglutinate  cyanosis + pain in the peripheries (ears, nose, fingers, toes), Raynaud’s phenomenon

Question 7

Causes of

AIHI

Non-immune haemolytic anaemia

Answer 7

AIHI (spherocytes) 
•	Associated with systemic diseases involving immune system
o	Malignancy e.g. Lymphoma, CLL
o	Auto-immune e.g. SLE
o	Infection e.g. mycoplasma 
o	Idiopathic

Non-immune haemolytic anaemia
Infection
MAHA (red cell fragments)

Question 8

What is MAHA?

Causes

Answer 8

MAHA is microangiopathic haemolytic anaemia
non-immune acquired haemolytic anaemia

DIC, TTP, HUS, pre-eclampsia, eclampsia
Underlying adenocarcinoma (causes low grade DIC)

Question 9

HUS triad

TTP pentad

causes

Answer 9

HUS
E.coli toxin O157 (shiga toxins/verotoxin)
 Circulating toxin binds to endothelial receptors  damaged endothelium  thrombin + fibrin deposited in microvasculature  erythrocytes damaged as they pass through partially occluded small vessels  haemolysis

MAHA
AKI
Thrombocytopenia

TTP
	Deficiency of VWF cleaving enzyme (ADAMTS-13)  unusually large VW multimers  platelet aggregation + damaged erythrocytes  thrombocytopenia + thrombi 
	Prodrome resembling flu like illness
MAHA
AKI
Thrombocytopenia
Neurological symptoms 
Fever

Both cause MAHA
Both normal PT, PTT

Question 10

Malignancy associated with eosinopilia

Answer 10

Hodgkin’s lymphoma
NHL
CML

Question 11

Acquired somatic mutation type 1

Answer 11

•	Mutations in tyrosine kinase genes
•	Cause excess proliferation
•	Cells are mature 
•	No effect on differentiation 
o	CML
o	MPD – myeloproliferative disorder
o	BCR-ABL  CML
o	JAK2 – polycythaemia vera (JAK2 V617F mutation)

Question 12

Acquired somatic mutation type 2

Answer 12

• Mutations in nuclear transcription factors
• May block differentiation – no healthy mature cells, all cells are immature
• If present with a proliferation mutation, can cause acute leukaemia
o PML RARA – abnormal fusion gene sequence associated with acute promyelocytic leukaemia

Question 13

4 things that can be used t help make a haemato-oncology dx

Answer 13

Morphology
Immunophenotype
Cytogenetics - prognostic information
Molecular genetics - mutation detection

Question 14

Markers

Mature T helper cell
Mature T killer cell
T cells
B lineage
activated B cell
Plasma cell
T regulatory cells
NK cells

Answer 14

Mature t helper cell markers --> CD3 CD4
Mature T killer cell --> CD3 CD8
T cells --> CD3, CD5
B lineage --> CD19*, CD20
activated B cell --> CD19 CD25, CD30
plasma cell --> CD138
T regulatory cells --> CD25, Foxp3
NK cells --> CD3 neg, CD56+ CD16+

All B cells express CD19 except plasma cells

https://www.abcam.com/primary-antibodies/b-cells-basic-immunophenotyping

Question 15

Surface IgG positive on cells

normal or abnormal?

Answer 15

normal

Question 16

marker of immaturity

Answer 16

tdt +ve

present o very earl B cells, precursour B cell neoplasms

(terminal deoxynucleotidyl transferase)