The scope of clinical haematology

Question 1

What are the componants of blood?

Answer 1

○ Red blood cells
○ Buffy coats
- Platelets
- White cells or leukocytes 
○ Plasma
- Clotting or coagulation factors
- Albumin
- Antibodies

Question 2

What are the functions of blood?

Answer 2

○ Transportation
- In red cells 
□ Gases​
® Oxygen and carbon dioxide​
- In plasma
□ Nutrients​
□ Waste​
□ Messages​
○ Maintaining vascular integrity 
- Platelets and clotting factors
□ Prevention of ​leaks​
- Anticoagulants and fibrinolytics 
□ Prevention of ​blockages​
○ Protection for pathogens
- Granulocytes/ monocytes
□ Phagocytosis​ and killing​
- Lymphocytes 
□ Antigen recognition ​and antibody formation​

Question 3

What are stem cells?

Answer 3

○ totipotent​
○ self-renewal​
○ Home to marrow niche​
- CXCR4 (antagonist plerixafor)​
○ Binary fission and flux through differentiation pathways amplify numbers​
○ Flux regulated by hormones / growth factors ​
- Some used therapeutically (erythropoietin, G-CSF, thrombopoietin agonists)​
○ Stem cell properties can now be ‘induced’​

Question 4

How are erythrocytes made?

Answer 4

Erythroblast–> reticulocyte (for about 24 hours)–> erythrocyte​

Question 5

where and why is erythropoietin made?

Answer 5

made in kidney in response to hypoxia

Question 6

What does reticulocyte count measure?

Answer 6

• A measure of red cell production

- If the red cell half life is very short there is an increase in reticulocytes

Question 7

What are platelets?

Answer 7

○ Function=haemostasis (and immune)​
○ Production from megakaryocytes and regulated by thrombopoietin​
- Produced in liver​
- Regulation by platelet mass feedback​
- Agonists (romiplostim, eltrombopag) used therapeutically​
○ Lifespan =7 days​

Question 8

What are neutrophils?

Answer 8

○ Function: to ingest and destroy pathogens, especially bacteria and fungi​
○ Interleukins (‘between white cells’) and CSFs (colony stimulating factors)​
- granulocyte-colony stimulating factor (G-CSF)(GM-CSF)​
○ regulation by immune responses ​
- Macrophages, IL-17​
○ Lifespan =1-2 days​
○ Speed of response=few hours​

Question 9

How are neutrophils made?

Answer 9

1. Blast (acute myeloid leukaemia)
2. Promyelocyte
3. Myelocyte
4. Metamyelocyte
5. Neutrophil

Question 10

What is neutrophilia?

Answer 10

• Production regulated by granulocyte-colony stimulating factor (G-CSF) ​
• Infection​
  □ Left shift, toxic granulation​
• Inflammation​
  □ e.g. MI, postoperative, rheumatoid arthritis​
• G-CSF used therapeutically​
  □ Neutropenia​
  □ Mobilisation of stem cells

Question 11

What is neutropenia?

Answer 11

• ‘Racial’​
• Decreased production​
  □ Drugs​
  □ Marrow failure​
• Increased consumption​
  □ Sepsis​
  □ Autoimmune​
• Altered function​
  □ e.g. chronic granulomatous disease​

Question 12

What are monocytes?

Answer 12

> the “reticuloendothelial system”
○ Function: to ingest and destroy pathogens, especially bacteria and fungi​
○ Subset of monocytes migrate into tissues and become macrophages​
- lifespan of many months​
- Some populations of macrophages self-maintaining​
○ dendritic cells ​
○ lifespan weeks

Question 13

Other than monocytes and neutrophils, name some myeloid cells

Answer 13

○ Eosinophils​
- parasites​
- allergy​
○ Basophils​

Question 14

What are lymphocytes?

Answer 14

○ Adaptive, versus innate, immune system​
- Immunological memory​
○ Surface antigens: CD markers​
○ Subtypes​
- B cells: make antibodies​
- T cells: Helper, cytotoxic, regulatory​
- NK cells​
○ Produced in bone marrow​
- B cells mature in bone marrow, T cells in thymus ​
○ Circulate in blood, lymph and lymph nodes​
○ Differentiate into effector cells in secondary lymphoid organs (lymph nodes or mucosal associated lymphoid tissue)​

Question 15

What is lymphocytosis?

Answer 15

• Infectious mononucleosis​

- Pertussis​

Question 16

What is lymphopenia?

Answer 16

• Usually post-viral​

- lymphoma​

Question 17

Explain positive and negative selection of lymphocytes

Answer 17

• In the bone marrow ​
• if gene rearrangement results in a functional receptor the cell is selected to survive: positive selection​
• If the receptor recognises ‘self’ antigens : the cell is triggered to die
• Negative selection: tolerance​
• B cells that survive this selection are exported to the periphery​

Question 18

What are human leukocyte antigens?

Answer 18

○ Class I: displays internal antigens on all nucleated cells​
○ Class II: displays antigens eaten by professional antigen presenting cells​
○ Constant within, variation between individuals

Question 19

What diagnostic tools does haematology have?

Answer 19

○ FBC
- Haemoglobin
□ Male: 135-170g/L
□ Female: 120-160g/L
- Platelets 
□ 150-400 x 10^9/L
- WBC
□ 4-10 x 10^9/L
○ Clotting times for clotting factors
○ Bleeding times for platelets 
○ Chemical assays
- Iron (ferritin)​
- B12​
- Folate​
○ Marrow aspirate and trephine biopsy​
○ Lymph node biopsy​
- Other organ biopsy​
○ Imaging

Question 20

What haematological treatments are there?

Answer 20

○ Replacement​
- Blood​
- Haematinics​
- Coagulation factors​
- Plasma exchange​
○ Transplantation​
○ Drugs​
- Cytotoxics​
- Monoclonal antibodies​
- Inhibitors of cellular proliferation​
- Immunosuppressants​
- Inhibitors of coagulation​
- Inhibitors of fibrinolysis​

Question 21

What are the causes of splenomegaly?

Answer 21

- Infectious ​
□ acute e.g. EBV, CMV​
□ chronic bacterial e.g. TB, brucella, SBE​
□ chronic parasitic e.g. malaria, leishmaniasis, schistosomiasis​
- Haematological-malignant​
□ various leukaemias and lymphomas​
□ myeloproliferative disorders​
- Portal hypertension​
- Haemolytic disorders​
□ hereditary spherocytosis, thalassaemia, haemoglobinopathies​
□ megaloblastic anaemia​
□ autoimmune​
- Connective tissue disorders​
□ SLE​
□ Felty syndrome
- Miscellaneous​
□ sarcoid​
□ malignant​
□ amyloid​
- Storage pool disorders​
□ Gauchers​
□ Niemann-Pick​

Question 22

What does hypersplenism mean?

Answer 22

Pancytopaenia

Question 23

What does hyposplenism mean?

Answer 23

• infections with encapsulated bacteria​

- red cell changes​

Question 24

When do you get thrombocytosis?

Answer 24

• In myeloid malignancies

- Reactive

Question 25

When do you get thrombocytopaenia?

Answer 25

• Marrow failure

- Immune destruction

Question 26

When are throbocytes functions alstered?

Answer 26

Aspirin, clopidigrel etc.

Question 27

What are antibodies?

Answer 27

• Adaptors between pathogens and clearance systems: opsonisation
  □ “Kiss of death”