Haematology II Flashcards
What are the phases of the haemostatic response?
- vasoconstriction
- platelet adhesion and aggregation
- clotting/coagulation phase
What does vasoconstriction do?
Help to control blood flow to a damaged area and limits blood loss
What does the coagulation phase take place on?
the primary platelet plug
How do the clotting phases communicate?
- through continuous feedback and feedforward
- one phase doesn’t have to stop for the other to start
Give features of platelets
- Small, oval, no nucleus (limited lifespan)
- 2-3 um in diameter
- Contains granules (allow platelets to take part in haemostasis
- Produced from Myeloid cell line
- Lives for about 7-10 days
- Variety of function essential to the normal process of haemostasis
How are platelets produced?
- they are produced from the cytoplasm of Megakaryocytes
- The cytoplasm fragments and produces platelets
- One megakaryocyte can produce about 4000 platelets
Where is thrombopoietin (TPO) produced?
- Mainly in the liver
- some in the kidneys
What controls the production of platelets?
- number of platelets already in circulation
- low number of platelets leads to increased thrombopoietin which increases platelet formation
What does thrombopoietin do?
regulates the differentiation of megakaryocytes and platelet formation
What happens when platelets are exposed to collagen?
- platelet adhesion (binding) takes place)
- this causes platelets to be activated. They change shape, secrete granule content and activate GPllb/lla
What happens after the platelet activation phase?
- serotonin is released which leads to vasoconstriction
- Thromboxane A2 and ADP are released which leads to platelet aggregation phase (ADP causes the platelets to swell so they come into contact with other platelets)
- Platelet phospholipid is released which leads to the blood coagulation cascade
What is the coagulation phase
The endpoint. The conversion of soluble plasma protein to the insoluble rigid polymer fibrin
Why can’t the fibrin clot be broken down the same way as the platelet plug was?
It is insoluble
What is released when there is damage to blood vessel surface?
Tissue factor
What are the different pathways in the coagulation phase?
- Extrinsic
- Intrinsic
- Common: intrinsic and extrinsic come together to activate factor X
What happens when clotting factors/coagulation enzymes are activated and how can you tell it has been activated?
- Activated when they are taking part in production of a clot
- turns the clotting factors into an enzyme
- once this has been activated it activates the next in the sequence
- When there is an ‘a’ at the end of the clotting factor name it shows it has been activated
What happens with the extrinsic pathway?
- activated by exposure of tissue factor on damaged blood vessel surface
- exposes tissue factor to the circulation
- comes into contact and binds with factor VII and forms tissue-factor - FVIIa complex
- this then binds to FX and activates it turning it into FXa
- fast pathway
What happens with the intrinsic pathway
- Negatively charged collagen activates the clotting factors that come into contact with it
- Factor XII activated to become XIIa
- Platelet factor 3 released by aggregated platelets forming on the surface of the damaged blood vessel wall
- This allows allow activation of Factor VIII and factor IX which combine together (Factor X activator complex) to allow activation of FX to FXa
- Slightly slower than extrinsic pathway
What does prothrombinase consist of?
FXa and FCa as co-factors
What happens in the common pathway?
- Prothrombin is activated to from thrombin
- Thrombin converts fibrinogen to fibrin
- we then produce out fibrin clot
Thrombin plays a big part in the feedback process. What clotting factors does it activate?
- FVIII and FIX which then allows them to take part in the intrinsic pathway
- FV to take part in the common pathway
- Also activates platelets which allows them to produce the platelet plug on which the fibrin clot can form
Why will any disorder that decreases Ca2+ concentration impair blood clotting?
Because calcium is needed for almost every part of the clotting process
What is vitamin K necessary for?
production of certain clotting factors in the liver including prothrombin
What are the anticoagulants we have in normal plasma>
- Antithrombin: inhibits thrombin (among other factors) that is not bound to fibrin
- Heparin - released by basophils and mast cells - co-factor that accelerates the actions of antithrombin
- both work on the intrinsic pathway
What is fibrinolysis?
When the fibrin clot is broken down
What happens in fibrinolysis?
- You have large amounts of plasminogen incorporated into your clot that are inactive until they get a signal indicating it is time to break the clot down
- When plasminogen is activated plasmin is produced
- plasminogen is activated by TPA which converts plasminogen to plasmin
- happens about two days after the clot forming and happens over several days until the clot is dissolved
What is plasmin?
Fibrin digesting enzyme
How many blood group systems do we have and how are they determined?
- 35 blood group systems
- genetically determined by antigens on red blood cell membrane
What are the blood groups of most clinical significance?
ABO and Rh (D) blood group systems
What are the different ABO blood groups and their characteristics?
- A: A antigen, Anti-B antibodies
- B: B antigen, Anti-A antibodies
- AB: A and B antigens, No antibodies
- O: None, Anti-A and Anti-B antibodies
When are antibodies for the ABO blood group produced?
In relation to the environmental substances you are exposed to
What would happen if type B blood cells came into contact with Anti-B antibodies>
the Anti-B antibodies would bind with the surface B antigen causing the to clog together (agglutination) and then this causes the red blood cells to break down – haemolysis
How do you test for a blood type?
you put a serum of one blood in another and see if there is agglutination
What would happen if you were exposed to a different blood group from your own?
Your red blood cells would break down
What are the genetics behind blood group inheritance?
- A and B genes are dominant and codominant
- O gene is recessive
What are the two groups of the Rh (D) blood group and what is this determines by?
- Rh negative (-) or Rh positive (+)
- Determined by presence or absence of the D antigen
An Rh(-) individual will not usually contain anti-Rh (D) antibodies. What does getting the antibodies require and what does this happen by?
Sensitisation by exposure to Rh+ RBCs
This may happen by:
- transfusion
- pregnancy
What is Haemolytic disease of the new born?
- Rh- mother
- Rh+ foetus
- during pregnancy you are hopeful that the maternal and foetal blood don’t mix
- during labour there is often mixing of the two circulations (haemorrhaging)
- there is then maternal antibody production (anti-Rh)
- normally takes about 72 hours for antibody production to reach a significant enough level to do damage
- so it doesn’t do damage in the first pregnancy but antibodies will stay in the maternal circulation
- So if the mother’s second pregnancy is with an Rh+ foetus as soon as their blood mixes the antibodies will attack the baby’s red blood cells and can cause significant anaemia
- this could happen either during the pregnancy or during labour
What are the important things to remember with blood donation and transfusion?
- Blood donation rule: always give someone their own blood group (red blood cells) where positive
- In an emergency – transfuse with O Rhesus negative: universal donor (No ABO antigens and no rhesus antigens so can’t be attacked)
Platelets contain filaments of actin and myosin. What happens after a blood clot has formed?
platelet filaments contracts to shrink the clot and reduce the size of the break in the vessel wall
What is platelet production called?
Thrombocytopoiesis
Where does Thrombocytopoiesis take place?
In the red bone marrow
What are the three substances that affect the rate of platelet formation and megakaryocyte activity?
- Thrombopoietin (TPO)
- Interlukin-6 a hormone that stimulates platelet formation
- Multi-CSF which stimulates platelet production by promoting megakaryocyte formation and growth
What happens during the vascular phase (vasoconstriction) of heamostasis?
- The endothelial cells contract and expose the underlying basement membrane to the bloodstream
- The endothelial cells begin releasing chemical factors and local hormones such as ADP, tissue factor and prostacyclin. Endothelial cells also release peptide hormones called endothelins which stimulate smooth muscle contraction and stimulate the division of endothelial cells, smooth muscle cells and fibroblasts to accelerate the repair process
- In small capillaries endothelial cells on opposite sides of the vessel may stick together and prevent blood flow along the damaged vessel
What happens at the start of the platelet phase?
- phase the platelets attach to sticky endothelial surfaces, to the basement membrane to exposed collagen fibres
- The attachment of platelets to exposed surfaces is called platelet adhesion. As more platelets arrive they stick to each-other as well this forms the platelet plug
What do platelets release when they are activated?
- ADP which stimulates platelet aggregation and secretion
- Thromboxane A2 and serotonin which stimulates vascular spasms
- Clotting factors
- Platelet derived growth factor that promotes vessel repair
- Calcium ions
What is the growth of the platelet plug limited by?
- Prostacyclin – a prostaglandin that inhibits platelet aggregation and is released by endothelial cells
- Inhibitory compounds released by WBCs entering the area
- Circulating plasma enzymes that break down ADP near the plug
- Compounds that when abundant inhibit plug formation e.g. serotonin
where does the extrinsic pathway begin?
Outside the bloodstream in the vessel wall?
Where does the intrinsic pathway begin?
Inside the bloodstream
What feedback system is involved with blood clotting?
Positive feedback system
Thrombomodulin is released by endothelial cells. What does it do?
This protein binds to thrombin and converts it to an enzyme that activates protein C. Protein C is a plasma protein that inactivates several clotting factors and stimulates the formation of plasmin
What does aspirin do in regards to blood clotting?
interferences with blood clotting and prolongs bleeding time. It inhibits platelets from producing prostaglandins and thromboxane A2 which stimulates new platelet activation and aggregation
Where do we get half our daily vitamin K requirement from?
Our diet
What does clot retraction do?
pulls the torn edges of the vessel closer together. This process reduces residual bleeding and stabilizes the injury site. It also reduces the size of the damaged area, making it easier for fibroblasts, smooth muscle cells and endothelial cells to complete repairs
What are the surface antigens involved in blood groups?
Integral membrane glycoproteins
What is a cross reaction or transfusion reaction?
is when during a transfusion an antibody meets its specific surface antigen and the RBCs agglutinate and may also haemolyze
What does a compatibility test usually involve?
- A determination of blood type
2. A cross-match test
