Haem: Haem changes in systemic diseases and intro to haemopath

Question 1

What is it called when there is a def in Factor 8

Answer 1

Haemophilia A

Question 2

What is it called when there is an excess of Hb

Answer 2

Polycythaemia - Due to hypoxia or EPO secreting tumour

Question 3

What is it called when there is an excess of granulocytes

Answer 3

CML or reactive eosinophilia

Question 4

What is it called when there is an excess of lymphocytes

Answer 4

CLL

Question 5

What is it called when there is a def of lymphocytes

Answer 5

Lymphopenia (HIV)

Question 6

What is it called when there is an excess of platelets

Answer 6

Essential thrombocythemia

Question 7

What is it called when there is a def of platelets

Answer 7

ITP

Question 8

What can cause anaemia?

Answer 8

Vit B12 or iron def

Question 9

What is the difference between primary and secondary haem disorders?

Answer 9

Primary - Germline or somatic mutations affecting bone marrow
Secondary - Changes in haem parameters secondary to a non haem disease

Question 10

What are some germline mutations in haem?

Answer 10

Factor 9 def - Haemophilia B
B chain globulin chain production defect - B thalaseeaemia
VHL gene mutation in RBC - Chuvash polycythaemia

Question 11

What are some somatic mutations in haem?

Answer 11

JAK2 V617F mutation in RBC - Polycythaemia vera

BCR-ABL1 in myeloid granulocytes - Chronic myeloid leukaemia

Question 12

What are some examples of secondary haem disorders?

Answer 12

Immune haemolysis - Anti RBC antibodies

Anti-factor 8 auto antibodies - acquired haemophilia A

Question 13

What would the lab results for Fe def anaemia be?

Answer 13

Microcytic hypochromic
Reduced ferretin and transferrin saturation
Raised TIBC

The cause is always bleeding until proven otherwise

Question 14

What is leuco erythroblastic anaemia and what would the blood film results look like?

Answer 14

Precursor to RBC and WBC anaemia - variable degrees of anaemia

Teardrop RBC - abnormal size and shape of RBCs
Nucleated RBC
Immature myeloid cells

RBCs are supposed to lose their nucleus before leaving the bone marrow, so this shows that there is some level fo damage in the bone marrow

Question 15

What are the reasons for bone marrow infiltration

Answer 15

Malignant - Leukaemia, lymphoma, myeloma, metastatic cancers
Infection - Miliary TB, severe fungal infection
Myelofibrosis - Massive splenomegaly, dry tap on BM aspirate

Question 16

What are some common features of haemolytic anaemia?

Answer 16

Reticulocytes
Raised unconjugated bilirubin
LDH raised
Haptoglobins lowered

Question 17

What could be cause of haemolytic anaemia?

Answer 17

Sickle cell, malaria, auto immune, G6PD

Question 18

What are the 2 groups of haemolytic anaemia?

Answer 18

Inherited and acquired

Question 19

What are some causes of inherited haemolytic anaemia?

Answer 19

Membrane defect - Hereditary spherocytosis
Cytoplasm/Enzyme defect - G6PD deficiency
Hb defect - Sickle cell disease, Thalassemia

Question 20

What are the 2 types of acquired haemolytic anaemia?

Answer 20

Immune - DAT/coombs test positive

Non-immune

Question 21

What would you see in autoimmune haemolytic anaemia

Answer 21

Spherocytes

DAT +ve

Question 22

What are some associated diseases with autoimmune acquired haemolytic anaemia

Answer 22

Lymphoma, CLL, SLE, mycoplasma

Question 23

What are some causes of non-immune acquired haemolytic anaemia

Answer 23

Malaria

MAHA

Question 24

What is particularly concerning about MAHA

Answer 24

It could be due to underlying adenocarcinoma or haemolytic uraemic syndrome in children due to E coli infection

Question 25

What would you see on MAHA blood film?

Answer 25

RBC fragments | Thrombocytopaenia

Question 26

When would you see spherocytosis?

Answer 26

Inherited or autoimmune haemolytic anaemia

Question 27

How would any malignant metasteses to the the bone marrow present?

Answer 27

Low Hb, low reituculocytes, high conjugated bilirubin

Question 28

What can cause neutrophilia?

Answer 28

``` Underlying neoplasm Corticosteroids Inflammation Myeloproliferative/Leukaemic disorders Pyogenic infections (pus forming bacteria) ```

Question 29

When there is neutrophilia, what are the 2 causes?

Answer 29

Infection/ Reactive or Malignant

Question 30

What would you see in neutrophils in an infection?

Answer 30

No immature cells Raised neutrophils Toxic granulation

Question 31

What would you see in neutrophils in CML?

Answer 31

Neutrophilia + basophils + Immature myelocytes

Question 32

What would you see in neutrophils in AML?

Answer 32

Neutrophilia + Myeloblasts

Question 33

What can cause reactive eosinophilia?

Answer 33

Parasitic infection Allergic diseases Underlying neoplasms - Hodgkin's, T cell NHL Drug reactions (erythema multiforme)

Question 34

What do pox viruses generally cause

Answer 34

Basophilia

Question 35

What happens in chronic eosinophillic leukaemia

Answer 35

FIP1L1-PDFGRa fusion gene

Question 36

What can cause monocytosis

Answer 36

TB, Brucella, typhoid CMV, varicella zoster sarcoidosis Chronic myelomonocytic leukaemia

Question 37

What can cause lymphocytosis

Answer 37

EBV, CMV, toxoplasma, hepatitis, rubella, herpes,sarcoidosis

Question 38

What can cause lymphopaenia

Answer 38

HIV, chemo

Question 39

When can you see mature lymphocytes in blood

Answer 39

Glandular fever, CLL, NHL - small lymphocytes and smear cells

Question 40

When can you see immature lymphocytes / lymphoblasts

Answer 40

ALL

Question 41

How do you differentiate between healthy/reactive polyclonal lymphocytosis and monoclonal lymphocytosis

Answer 41

Healthy/reactive - 60:40 split kappa and lambda expressing cells Monoclonal - 90% either kappa or lamda - malignancy

Question 42

What are the 4 stages of testing you go through for haem cancers

Answer 42

Morphology Immunophenotype Cytogenetics Molecular genetics

Question 43

What happens in myeloproliferative neoplasm (chronic)

Answer 43

There is an overproliferation of neutrophils

Question 44

What happens in acute myeloid leukaemia

Answer 44

Differentiation of myeloblasts is blocked, so you get an overproliferation of immature cells

Question 45

What are 3 types of acquired somatic mutations in leukaemia and lymphoma

Answer 45

Cellular proliferation - Mutation in tyrosine kinase (BCR ABL in CML and JAK2 in MPD) Blocked cellular differentiation Prolonged cell survival - BCL 2 and follicular lymphoma

Question 46

How do you differentiate between B cell acute lymphoblastic lymphoma and multiple myeloma

Answer 46

B cell acute lymphoblastic lymphoma - Tdt +ve, CD19 +ve, Surface Ig -ve Multiple myeloma - Tdt +ve, Surface Ig +ve, CD138 -ve