L9 - haemostasis

Question 1

define haemostasis

Answer 1

A multifactoral process in which bloodflow is stopped as a result of injury to prevent haemorrhage

Question 2

Haemostasis is a three step process. The first step is vasoconstriction - this reduces the blood pressure downstream of the insult, what are the following two steps

Answer 2

2) The primary haemostatic response - Formation of a primary haemostatic plug from activated platelets that stick to both the vessel and the underlying connective tissue - weak (second to minutes)
3) The secondary haemostatic response - Formation of the secondary haemostatic plug (Fibrin haemostatic plug, 30 mins)

Question 3

There are three steps in platelet activation - adhesion, activation and aggregation. Briefly describe each

Answer 3

Adhesion - Platelet adheres to subendothelial layer at site of insult via von willebrand factor binding its receptor
Activation - Contact with collagen in the underlying layer activates the platelets, platelets now release ADP which amplifies the response
Aggregation - Platelets change shape and cross link to form a plug

NOTE - Von willebrand factor is in the blood, receptor is sub-endothelial and receptor ligand complex allows contact with collagen

Question 4

Thrombocytopenia is a low platelet count in the blood, will the PT or APTT be raised?

Answer 4

No neither will be raised, it is the function of the platelets not the clotting cascade which is impaired

Question 5

Give two potential causes and the symptoms of thrombocytopenia

Answer 5

Causes - decreased platelets due to drugs/malignancies
Increased consumption of platelets due to infection/splenomegaly/DIC

Symtpoms - Petechia in the skin due to bleeding from small peripheral vessels

Question 6

How is fibrin activated, only the key components at the end of the clotting cascade need be discussed

Answer 6

Thrombin is the end product of the clotting cascade, it cleaves circulating fibrinogen to fibrin which then forms the secondary haemostatic plug

Question 7

Which pathway requires tissue factor released from damaged cells

Answer 7

Extrinsic pathway

Note - the intrinsic pathway doesn’t require vessel damage to occur

Question 8

Give an example of natural anticoagulants released as clotting is started

Answer 8

antithrombin/ protein C

Question 9

What plasma protein is responsible for fibrinolysis - a process which is activated immediately alongside clot formation?

Answer 9

plasmin which is the cleaved and activated form of plasminogen. Plasminogen is the circulating inactive form of plasmin

Question 10

which test assesses the extrinsic pathway PT or APTT?

Answer 10

PT - utilises tissue factor in a test tube to look at how long it takes a clot to form (tests common pathway too)

APTT looks at intrinsic and common pathway

Question 11

How are coagulation factor disorders treated

Answer 11

With recombinant forms of the deficient factor

Question 12

Give some symptoms of haemophilias A and B

Answer 12

Easy brusing/massive haemorrhage after surgery/joint deformities

Question 13

What would the results be to the following tests in a haemophiliac:
platelet count
PT
APTT

Answer 13

platelet counut - normal
PT - normal
APTT - prolonged
Intrinsic pathway is compromised

Question 14

Which factor is deficient in each haemophilia?

Answer 14

A - F VIII

B - F IX

Question 15

Give some common symptoms of vWB disease

Answer 15

Easy bruising/ spontaneous bleeds from mucous membranes/ prolonged bleeding after trauma

Question 16

What do we see clinically in vWB disease i.e. at factor level?

Answer 16

Reduced platelet adhesion to wall/
Reduced vWB and F VIII as vWB carries and protects this factor/
Raised bleeding time and APTT

Question 17

What levels are raised in DIC?

Answer 17

PT, APTT and raised D dimers

Question 18

What is DIC ?

Answer 18

A clotting activator gets into the blood from tissue damage causing bodywide microthrombi, it is a secondary complication causing excessive consumption of platelets and clotting factors as well as fibrinolysis

Question 19

What are DIC patients at high risk of and what is the treatment?

Answer 19

Great risk of bleeding and thrombosis due to excessive clotting - bleeding becasue of using up factors

Treat - heparin and possible platelet transufsion as they are used up AND TREAT THE UNDERLYING CAUSE

Question 20

Give an example of a condition that predisposes to DIC

Answer 20

severe trauma/ sepsis/ malignancy/ snake bite/ extensive burns

Question 21

What are thrombophilias ?

Answer 21

A set of conditions which predispose to thrombosis

Question 22

Other than ADP what else is released by platelets to amplify the activation response?

Answer 22

thromboxane A2

Question 23

How does aspirin work?

Answer 23

It inactivates an enzyme responsible for the production of thromboxane A2 and thus downregulates the clotting response

Question 24

How do the elements of the clotting cascade activate each other concurrently?

Answer 24

Proteolytic cleavage

Question 25

What does plasmin degrade fibrin too? When do we clinically measure this?

Answer 25

Many things but mainly D dimers | Thus we measure D dimers in patients with a suspected deep vein thrombosis, raised D dimers suggest a likely DVT/PE

Question 26

Therapeutically we take advantage of plasmin to break down clots, what plasminogen activator do we use clinically for this?

Answer 26

Streptokinase

Question 27

What inheritance pattern do we see in haemophilia?

Answer 27

X-linked recessive (need to look at first semester again to go over inheritance patterns)

Question 28

Describe the symptoms of haemophilia

Answer 28

Bleeding into muscles and joints/regular mucous membrane bleeds/easy bruising etc.

Question 29

What would coagulation tests show in haemophilia?

Answer 29

Prolonged APTT/deficient in the particular factor/normal platelet count, PT and bleeding time

Question 30

What is the inheritance pattern of vWB disease?

Answer 30

autosomal dominant

Question 31

Give an example of an inherited thrombophilia

Answer 31

Anticoagulant e.g. antithrombin deficiency

Question 32

What would you give to a patient who had overdosed on warfarin (note this is easy to do very narrow therapeutic range)?

Answer 32

Vitamin K - Warfarin is a vitamin K antagonist, there are many vitamin K dependent factors in the clotting cascade

Question 33

How does heparin work?

Answer 33

Binds to antithrombin to improve its ability in inactivating thrombin

Question 34

Give some symptoms of DIC

Answer 34

confusion/gangrene/renal failure/respiratory distress (end organ damage doe to poor blood flow from microthrombi

Question 35

Calcium is an important co-factor required for clotting

Answer 35

T

Question 36

Prothrombin requires Vitamin K for its synthesis

Answer 36

T

Question 37

What is INR and what is it used for?

Answer 37

Calculated from PT, gives an indication of how well anticoagulant therapy is working

Question 38

What is trousseaus syndrome?

Answer 38

an acquired thrombophilia due to disseminated cancer - cancer causes hypercoagulability and endothelial damage. Two important prongs of virchow's triad for thrombosis.

Question 39

Give symptoms of a DVT

Answer 39

- pain and tenderness in one of your legs (usually your calf) - swelling - a heavy ache in the affected area. - warm skin in the area of the clot. - red skin, particularly at the back of your leg below the knee.

Question 40

How does a DVT form?

Answer 40

Immobility or whatever causes stasis of blood -> increased risk of thrombosis -> formation of a thrombus

Question 41

What are some risk factors for DVT?

Answer 41

the combined contraceptive pill/surgery/pregnancy/immobility/dehydration