Week 3-haemostasis Flashcards

1
Q

What does the term haemostasis mean?

A

Arrest of bleeding and the maintenance of vascular patency.

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2
Q

What are the four requirements of haemostasis?

A

Permanent state of readiness

Prompt response

Localised response

Protection against unwanted thrombosis.

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3
Q

What makes up primary haemostasis?

A

Formation of the platelet plug

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4
Q

What makes up secondary haemostasis?

A

Formation of the fibrin clot.

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5
Q

What occurs after secondary haemostasis?

A

Fibrinolysis- the clot is broken down (to maintain patency of the blood vessels)

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6
Q

What are anticoagulant defences?

A

They are proteins that switch off the coagulation pathway.

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7
Q

Where are platelets formed?

A

In the bone marrow, they bud off from megakaryocytes.

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8
Q

Do platelets have a nucleus?

A

No they are anucleated.

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9
Q

What is the life span of a platelet?

A

7-10 days.

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10
Q

Describe the process that leads to platelet adhesion (not aggregation) after injury?

A

Endothelial (vessel wall) damage leads to exposure of collagen and releases Von Willebrands Factor and other proteins to which platelets have receptors for. This leads to platelet adhesion at the site.

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11
Q

Describe how the platelets then aggregate to form the platelet plug?

A

The platelets already adhered to the site release chemicals which cause other platelets to stick to them. Forming the platelet plug.

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12
Q

What kind of injury is primary haemostasis in response too?

A

Small injuries e.g. paper cuts. If you have a larger injury the platelet plug won’t hold so you need a fibrin clot to form.

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13
Q

When might you have failure of primary haemostasis (platelet plug formation)?

A

Vascular issue (the vessel itself could be deficient in collagen)

Platelets- reduced number (thrombocytopenia), reduced function (drug induced)

Von Willebrand Factor (this acts as a glue that sticks the platelets together, without this you cant get aggregation).

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14
Q

What is a condition when you get decreased collagen in vessel walls?

A

Henloch Schonlein Purpura

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15
Q

What are the consequences of having a failure in platelet plug formation?

A

Spontaneous bruising and purpura (mostly lower limbs due to gravity- this is where the blood leaks out)

Mucosal bleeding- e.g. nose bleeds, GI bleeding, conjunctival bleeding, heavy periods

If the platelets arent working at all- intracranial haemorrhage

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16
Q
A
17
Q

What are the screening tests for primary haemostasis?

A

PLATELET count

Only simple one that can be done- could check VWF levels etc.

18
Q

Describe the initiation stage of forming the fibrin clot?

A

Platelets secrete calcium onto their surface which is positively charged. Circulating clotting factors are all negatively charged so they will come and stick to the platelets. They start off inactive, and when they stick they become active.

When you get tissue damage, tissue factor (TF) is released from damaged tissues. TF activates clotting factor number VII, which in turn activates factor V and X.

19
Q

Describe the propagation stage of forming the fibrin clot?

A

Factor X and V work to break down prothrombin into its active form, thrombin. Thrombin cleaves fibrinogen to form fibrin. However only a small amount of fibrin is produced.

20
Q

Describe the amplification stage of the formation of the fibrin clot.

A

The thrombin generated also activates factor VIII and IX which then activates more factor V and X which then creates more thrombin and therefore more fibrin. This means the plug formed is of substantial size.

21
Q

What is prothrombin also known as?

A

Clotting factor II.

22
Q

What can cause failure of the fibrin clot?

A

Single clotting factor deficiencies (usually hereditary e.g. haemophillia)

Multiple clotting factor deficiencies (usually acquired e.g. DIC)

Increased fibrinolysis (usually part of complex coagulopathy)

23
Q

Describe the process of fibrinolysis?

A

Tissue plasminogen factor activates plasminogen to form plasmin. This then breaks down the fibrin to form fibrin degredation products.

24
Q

What blood test can measure the amount of clot breakdown occuring?

Why do these also reflect clot formation?

Why is it not a reliable test?

A

D-dimers- these are the crosslinked form of fibrin degredation products.

As soon as a clot is formed it starts to be broken down again, therefore if d-dimers are raised it is likely that there was a clot.

D-dimers are raised in lots of things.

25
Q

If you have a low D-dimer, does this rule out blood clots?

A

Pretty much yes. D dimers will be raised if there was a clot formed, however high d dimers is not specific.

26
Q

What are the consequences of failure of fibrin clot formation?

A

There is no characteristic clinical syndrome- it depends on the underlying cause.

Patients may have a combined primary and secondary haemostatic failure.

Pattern of bleeding will depend on clotting factors affected.

27
Q

If there is a single clotting factor deficiency, where is the bleeding likely to occur?

A

Likely to occur into joints and muscles. Classicly the ones that weight bear more e.g. ankle, knee, elbow. This is due to small tears occuring in the muscles all the time, normal people respond to this by forming a fibrin clot however in patients with a clotting factor deficiency, this doesnt occur.

28
Q

Which screening tests can be used for testing the fibrin clot formation ability of a patient?

A

Prothrombin time (PT)

Activated partial thromboplastin time (APTT)

29
Q

Which pathway (intrinsic or extrinsic) does prothrombin time test?

A

Extrinsic pathway.

30
Q
A
31
Q

Describe how prothrombin time is carried out?

A

A blood sample is taken. Add excess tissue factor, calcium and phospholipid will push it down the left side. This will be testing factors VII, V, X, prothrombin and thrombin.

(you add excess TF, calcium and phospholipid to make sure these are not the limiting factors in the reaction).

32
Q

What do you add to push it down the intrinsic pathway? Which clotting factors are being tested now?

A

Kaelin

Tests factor VIII and IX.

33
Q

Some drugs only affect the right hand side (intrinsic pathway), give an example?

A

Heparin.

34
Q

What is the main naturally occuring anticoagulant, and how does it work?

A

A serine protease inhibitor, called antithrombin, it binds to a switches off thrombin, and also stops other clotting factors.

35
Q

What other naturally occuring anticoagulants are there? Describe their function?

A

Protein C and protein S.

Once the blood clot has formed, it produces thrombomodulin. This activates protein C and protein S to switch off blood clotting. Protein C and protein S switch off factor VIII and V.

36
Q

What is thrombophillia?

A

A deficiency of naturally occuring anticoagulants. This means patients have an increased tendency to develop venous thrombosis.