Haematology Flashcards
What are the blood components and products?
Plasma - Clotting or coagulation factors, albumin, antibodies.
Buffy coat - platelets, white cells or leucocytes.
Red Blood Cells
What does blood transport?
RBC - gases - oxygen and carbon dioxide.
Plasma - Nutrients, waste, messages.
How does blood allow maintenance of vascular integrity of the blood?
Prevention of leaks - platelets and clotting factors.
Prevention of blockages - anticoagulation and fibrinolytics.
How does the blood protect from pathogens?
Phagocytosis and killing - granulocytes and monocytes.
Antigen recognition and antibody formation - lymphocytes.
What do haematological abnormalities mean?
High levels:
Increased rate of production, decreased rate of loss.
Low levels:
Decreased rate of production, increases rate of loss.
Altered function.
Describe stem cells
Totipotent
Self-renewal
Home to marrow niche
Binary fission and flux through differentiation pathways amplify numbers.
Flux regulated by hormones/growth factors.
Stem cell properties can now be “induced”
What does a erythroblast become when it is differentiated?
Reticulocyte and then erythrocyte.
What is reticulocyte count?
Measure of red cell production.
When is erythropoietin made?
In kidney in response to hypoxia.
What are the consequences of anaemia?
Poor gas transfer: dyspnoea and fatigue.
Decreased production.
Increased loss.
What red cells are there?
Microcytes, macrocytes
Polychromasia
Burr cells in renal failure.
What is the function of platelets?
Haemostasis (immune)
Production regulated by thrombopoietin - produced in liver.
Lifespan of 7 days.
What is the function of neutrophils?
To ingest and destroy pathogens, especially bacteria and fungi.
Interleukins and CSFs.
Regulation by immune responses.
Lifespan = 1-2 days
Speed of response is few hours.
What are the cells in differentiation of neutrophil?
- Blast
- Promyelocyte
- Myelocyte
- Metamyelocyte
- Neutrophil.
What is neutrophilia?
Elevated neutrophil count.
Production regulated by granulocyte-colony stimulating factor.
Bacterial Infection most common cause - left shift, toxic granulation.
Inflammation.
G-CSF used therapeutically.
What is Neutropenia?
Low neutrophil count.
Decreased production - drugs, marrow failure.
Increased consumption - sepsis, autoimmune.
Altered function
What is the function of monocytes?
To ingest and destroy pathogens, especially bacteria and fungi.
Subset monocytes migrate into tissues and become macrophages.
What are lymphocytes?
Adaptive, versus innate, immune system.
Surface antigens: CD markers.
What is Lymphocytosis?
High level of lymphocytes - acute viral infection.
- Pertussis
- Infectious mononucleosis.
What is Lymphonopenia?
Low levels of lymphocytes
- usually post-viral
- lymphoma
What are the subtypes of lymphocytes?
B cells - make antibodies
T cells - Helper, cytotoxic, regulatory
NK cells
Where are lymphocytes produced?
Bone marrow
B cells mature here
T cells mature in thymus.
What are antibodies?
Antibodies are proteins produced and secreted by B cells. They bind to foreign substances that invade the body, such as pathogens.
What is positive selection?
In the bone marrow if gene rearrangement results in a functional receptor the cell is selected to survive.
What is negative selection?
If the receptor recognises”self”antigens - the cell is triggered to die. Tolerance.
What are the 2 classes of human leucocyte antigen?
Class 1: displays internal antigens on all nucleated cells.
Class 2: Displays antigens eaten by professional antigen presenting cells.
How do the immune cells read HLA on cells?
They read it to help identify self vs non self cells or uninfected vs infected cells.
Immune response triggered if infected cell in identified.
What can happen with
- Too much
- Too little
- Abnormal function of plasma?
- Paraproteins
- Clotting factors: haemophilia
- Clotting factors - haemophilia.
What are the diagnostic tools for blood?
Full Blood count Clotting times for factors and platelets. Chemical assays: Iron (ferritin) B12 Folate Marrow aspirate and trephine biopsy. Lymph node biopsy. Imaging.
What are some of the replacement treatments for Haematology?
Blood
Haematinics
Coagulation factors
Plasma exchange
What are the drug available for Haematology treatment?
Cytotoxics. Monoclonal antibodies. Inhibitors of cellular proliferation. immunosuppressants. Inhibitors of coagulation. Inhibitors of fibrinolysis.
Where do blood groups arise from?
Antigens = something that provokes an immune response.
Red cell antigens are expressed on the cell surface - can provoke antibodies.
What do blood group A have antibodies against?
Blood group B
What do blood group B have antibodies against?
Blood group A
What blood group do O have antibodies against?
A and B
Blood group AB antibodies?
No antibodies against A or B
Group A can receive blood from who?
A and O
Group B can receive blood from who?
B and O
AB can receive blood from who?
A, B, AB and O
O can receive blood from who?
O
A can receive Fresh frozen plasma from who?
A, AB
B can receive fresh frozen plasma from who?
B, AB
AB can receive fresh frozen plasma from who?
AB
O can receive fresh frozen plasma from who?
A, B, AB, O
What are the RhD blood groups?
Either you are RhD positive or RhD negative depending on inheritance from parents.
What happens to RhD negative individuals if exposed to RhD positive cells?
Can make Anti- D
- Can cause transfusion reactions or haemolytic disease of the newborn.
When would you need a red cell transfusion?
- To correct severe actue anaemia.
- To improve quality of life in patient with otherwise uncorrectable anaemia.
- To prepare a patient for surgery or speed up recovery.
- To reverse damage caused by patients’s own red cells.
- Sickle Cell disease.
How are RBC stored, transfused?
Stored at 4 degrees celcius
Transfuse over 2-4 hours.
1 unit increments.
When are platelets needed?
Massive haemorrhage.
Bone marrow failure.
Prophylaxis for surgery.
Cardiopulmonary bypass.
How are platelets stored and transfused?
1 dose = 4 pooled or one apheresis donor.
Stored at 22 degrees celcius
Transfused over 20-30 minutes
Fresh frozen plasma indications
1 unit from 1 unit of blood.
Stored frozen, allow 30 mins to thaw.
Massive haemorrhage
DIC with bleeding
Prophylactic.
Cryoprecipitate.
What checks take place in blood bank?
Blood sample
Two sample policy
Group and screen - for allo-antibodies in serum.
Cross matching
How is the blood screened?
Gel columns and automation
Coombs test - direct vs indirect.
What is difference between direct and indirect Coombs test?
Direct = autoimmune haemolytic anaemia passive anti-D. Haemolytic transfusion reactions.
Indirect - Cross matching.
How is haemolytic disease of fetus and newborn (HDFN) managed and controlled?
- IgG crosses placenta.
Prevention using prophylactic anti-D - sensitising events.
Routine at 28/40.
Treatment by careful monitoring:
Antibody titres
Doppler ultrasounds
Intrauterine transfusions
Neonatal alloimmune thromvocytopenia - similar to platelets.
What are the substances required to make red cells?
Iron, copper, cobalt, manganese.
B12, folic acid, thiamine, Vit.B6, C, E
Amino acids
Erythropoietin, GM-CSF, androgens, thyroxine
How are red cells broken down?
Occurs in reticuloendothelia system.
Normal life span is 120days.
Iron-recycled into haemoglobin.
Haem - biliverdin - bilirubin.
bilirubin is boud to albumin in plasma from red cell breakdown.
What are mature red blood cells called?
Erythrocyte
Membrane, enzymes and haemoglobin
What forms the red cell membrane?
Skeletal proteins maintain the shape and deformability.
Defects in skeletal proteins can lead to increased cell destruction.
What is Hereditary Spherocytosis?
Most comm forms autosomal dominant.
Defects in 5 different structural proteins:
Ankyrin, alpha spectrin, beta spectrin, band 3, protein 4.2.
How does Heriditary Spherocytosis present and how is it treated?
Presents = anaemia, jaundice, splenomegaly, pigment gallstones.
Treatment = Folic acid, transfusion, splenectomy if severe anaemia.
What does glycolysis and pentose phosphate shunt do in red cell enzymes?
Provides energy.
Protects from oxidative damage.
What is the role of Glucose 6 phosphate dehydrogenase (G6PD)?
Protects red cell proteins from oxidative damage.
- produced NADPH - vital for reduction of glutathione.
What is G6PD deficiency?
Commonest disease causing enzymopathy in the world.
Cells vulnerable to oxidative damage.
Confers protection against malaria.
X linked - affects males and female carriers.
How does G6PD deficiency present?
Variable degree of anaemia. Neonatal jaundice Splenomegaly Pigment Gallstones. Drug, broad bean or infected precipitated jaundice or anaemia.
What can trigger haemolysis in G6PD deficiency?
Infection, acute illness.
Drugs - antimilarials, antibacterials, analgesics, Vit K.
What is the function of haemoglobin?
Gas exchange = O2 to tissues, CO2 to lungs.
Oxygen dissociation curve - shifts as a compensatory mechanism.
HbF higher O2 affinity that HbA.
What is adult haemoglobin (HbA) composed of?
Haem molecule and 2 alpha chains with 4 alpha genes and 2 beta chains with 2 beta genes.
HbA (aaBB) - 97%.
What are haemoglobinopathies?
Inherited abnormalities of haemoglobin synthesis.
Reduced or absent globin chain production. (Thalassaemia)
Mutations leading to structurally abnormal globin chain. (sickle cell)
What is sickle cell RBC composed of?
Haem and 2 alpha chains with 2 beta (sickle) chains.
What can occur in sickle cell?
Red cell injury - haemolysis - endothelial activation, promotion of inflammation, dysregulation of vasomotor tone by vasodilator mediators - leads to vaso-occlusion.
What is Thalassaemias?
Reduced or absent globin chain production.
Alpha and beta.
Chain imbalance.
What can be seen in Beta thalassaemia major?
Severe anaemia
- present at 3-6 months
- expansion of ineffective bone marrow
- bony deformities
- splenomegaly
- growth retardation
Treatment for beta thalassaemia major
Chronic tranfusion support 4-6 weekly. Normal growth and development. BUT iron overloading. Iron chelation therapy. Bone marrow transplantation-curative.
What factors influence the normal range of haemoglobin?
Age Sex Ethnic origin Time of day sample is taken Time to analysis
What are the normal ranges for 1. Women
2. Men
- 120-160
2. 140-180
What is the total body iron?
Approx 4g
Dietary intake balanced loss.
Most of body’s iron is in Hb - recycled.
No pathway for excretion of excess iron.
What happens during iron metabolism?
Absorbed iron - bound to mucosal ferritin and sloughed off OR transported across the basement membrane by ferroportin.
THEN bound to tranferrin in plasma.
STORED as ferritin mainly in the liver.
What is the role of hepcidin in iron metabolism?
Synthesised in hepatocytes in response to increased iron levels and inflammation. Blocks ferropotin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells.
What helps you to stop bleeding and form a clot?
Platelets, vWF, Coagulation factors.
What allows the clot to remain confined to the site of injury?
Natural Anticoagulants.
What allows the clot to vanish after 1 week?
Fibrinolytic system.
How does blood clot?
When an injury causes a blood vessel wall to break, platelets are activated. They change shape from round to spiny, stick to the broken vessel wall and each other, and begin to plug the break. They also interact with other blood proteins to form fibrin. Fibrin strands form a net that entraps more platelets and blood cells, producing a clot that plugs the break.
What is the role of platelets in haemostasis?
Adhere
Activation
Aggregation
Provide phospholipid surface for coagulation.
What are the different clotting agents?
Factors XII, XI, IX, VIII, X.
Prothrombin
Fibrinogen.
What happens in normal clotting sequence?
Fibrin net and platelet plugs at hole in vessel wall.
What happens in defective clotting sequence?
Haemophilia B (factor IX deficient) Haemophilia A (Factor VIII deficient) Hole in vessel wall.
What is the extrinsic factor in clotting?
Tissue factor.
What are the natural anticoagulants?
TFPI
Protein C and S
Antithrombin
What do you get forming at the vessel wall hole?
Fibrin clot and a platelet plug.
Clot is confined to the area of tissue damage.
What is Fribrinolysis?
The enzymatic breakdown of fibrin in blood clots.
clot lysis and tissue repair
What is the localised development of an appropriate clot?
Platelets
Von Willebrand Factor
Coagulation factors
What is the localised development limited by?
Natural Anticoagulants.
What is the clot cleared up by?
Fibrinolytic system.
How do Antithrombotic drugs act?
Principally by inhibiting platelet function directly (for example, aspirin, clopidogrel and dipyridamole) or, via thrombin inhibition, by inhibiting platelet activation and fibrin formation (for example, heparins, warfarin and direct inhibitors of thrombin or factor Xa).
What are the elements of Haemostasis?
Primary haemostasis
Blood coagulation
Fibrinolysis
What happens in primary haemostasis?
Vasocostriction
Platelet adhesion
Platelet aggregation
What happens in coagulation?
Insoluble fibrin formation.
Fibrin cross-linking
What is meant by thrombus?
Clot arising in the wrong place.
What is a thromboembolism?
Movement of a clot along a vessel.
What is Virchow’s Triad?
Stasis
Hypercoagulability
Vessel Damage
THROMBOSIS
What is von willebrand factor?
Blood glycoprotein involved in hemostasis, helps blood cells stick together when you bleed.
What are coagulation factors?
Proteins in the blood that help control bleeding.
The intrinsic pathway consists of factors I, II, IX, X, XI, and XII. Respectively, each one is named, fibrinogen, prothrombin, Christmas factor, Stuart-Prower factor, plasma thromboplastin, and Hageman factor. The extrinsic pathway consists of factors I, II, VII, and X. Factor VII is called stable factor.
3 - tissue factor.
12 - not as important.
How is thrombin activated?
From prothrombin that is naturally occurring.
Factor 10 brings the thrombin.
Ultimate goal is fibrin and we get it from thrombin.
What does thrombin activate in the coagulation cascade?
5,7,8,11,13.
End goal of the cascade is to get the fibrin molecules.
What does thrombin help make?
Plasmin - helps break the mesh parts break to stop so much being produced.
Anti-thrombin - decreases the amount of thrombin
What is the pathogenesis of haematological malignancy?
Multi step process.
Acquired genetic alterations in a long lived cell.
Proliferative/survival advantage to that mutated cell.
This produces the malignant clone.
The malignant clone grows to dominate the tissue. (e.g. bone marrow or lymph nodes)
What stem cells are involved in myeloid malignancies?
Red cells Platlets Basophils Monocytes Eosinophils Neutrophils
What stem cells are involved in Lymphoid malignancies?
B-cell - geminal center.
T-cell
What does the bone marrow in multiple myeloma show?
Plasmacytosis.
What are the key features of acute Leukaemia?
Leukaemic cells do not differentiates.
Bone marrow failure.
Rapidly fatal if untreated.
Potentially curable e.g. childhood acute lymphoblastic leukaemia.
Good prognosis acute myeloid leukaemia treated with chemo.
What are the key features of chronic leukaemia?
Leukaemic cells retain ability to differentiate.
Proliferation without bone marrow failure.
Survival for a few years.
Potentially curable with modern therapy.
e.g. Tyrosine Kinase Inhibitors in CML.
What is the structure of the lymph node?
Follicle - B cells. Paracortex - T cells Medulla - plasma cells Germinal centre - cells undergo expansion and selection. Mantle zone - naive cells Cortex Marginal zone.
What happens during B-cell maturation?
Progenitor B cell – Pre B cell – Immature B cell (bone marrow)
Plasma cell - immature B cell – Naive B cell (antigen).
Germinal centre – Immature B cell – Memory B cell.
