Thrombosis/coagulation: inherited and acquired

Question 1

what is haemostasis?

Answer 1

A reaction to stop blood loss, restore vascular integrity and preserve life

Question 2

what is disseminated intravascular coagulation?

Answer 2

Overactivity of clotting factors lead to clots forming in the bodys small blood vessels

Question 3

what are the risk of disseminated intravascular coagulation?

Answer 3

• the clotting factors and platelets have all been used up meaning there is now a risk of serious bleeding
• blockage of small blood vessels causing damage from lack of flow.

Question 4

what is the first thing that happens when a vessel is damaged?

Answer 4

Vascular spasm happens immediately to try and minimise blood flow

Question 5

what is the order of the main events in haemostasis?

Answer 5

vessel injury –> vascular spasm –> platelet plug forms –> coagulation

Question 6

what is primary haemostasis?

Answer 6

this is the formation of the first unstable clot from platelet adhesion and aggregation

Question 7

what is secondary haemostasis?

Answer 7

this is the formation of a secondary plug with fibrin from the coagulation cascade

Question 8

how are platelets formed?

Answer 8

the edges of megakaryocytes break off forming fragments

Question 9

what is the life span of a platelet?

Answer 9

7-10 days

Question 10

what granules do platelets contain?

Answer 10

alpha, dense and lysosomes

Question 11

what are the order of events that make up primary haemostasis?

Answer 11

platelet adhesion –> secretion –> aggregation –> contraction

Question 12

what is the initiation step in the coagulation process? t

Answer 12

tissue factor is released when the vessel wall is damaged, this leads to thrombin production which is the initiation

Question 13

what is adhesion?

Answer 13

Signalling molecules are exposed when the vessel is damaged, this attracts circulating platelets which attach to sub-endothelial tissue

Question 14

what is the secretion stage in haemostasis?

Answer 14

this comes after adhesion
the platelets become activated through the presence of thrombin and release more attractant chemicals which attracts more platelets

Question 15

what activates platelets?

Answer 15

thrombin

Question 16

what is aggregation?

Answer 16

this comes after the secretion stage. the new platelets that have been attracted bind to the previously adhered platelets and then also become activated

Question 17

what triggers platelet production?

Answer 17

thrombopoitein

Question 18

what factors does antithrombin effect?

Answer 18

factor X

thrombin II

Question 19

what factors do activated protein C effect?

Answer 19

factor 8, factor V

Question 20

what does tissue factors pathway inhibitor inhibit?

Answer 20

inhibit FV11-TF complex and X

Question 21

what are the natural coagulation inhibitors?

Answer 21

Antithrombin
Protein C pathway
TFPI

Question 22

what is the process of fibrinolysis?

Answer 22

Plasmin is formed from tissue plasminogen activator. This causes the breakdown of fibrin

Question 23

what is phlebitis?

Answer 23

A thrombosis of the large veins in the leg causing a large swelling. Thought to be due to Protein S decreasing in pregnancy

Question 24

what aspects of virchows triad affect veins?

Answer 24

Stasis

blood coagulation

Question 25

what factors of virchows triad affect the arterial system?

Answer 25

vessel wall

Question 26

Are arterial thrombosis more likely to be red or white?

Answer 26

White as they are mainly platelet based associated with changes in the vessel wall

Question 27

are venous thrombosis more likely to be red or white?

Answer 27

Red as fibrin based, coagulation factors are more important.

Question 28

what are the possible fates of a venous thrombus?

Answer 28

1. resolution
2. PE
3. organised and incorporated into the wall
4. organised and recanalized

Question 29

what is the main problem of a saddle thrombus?

Answer 29

This affects the pulmonary trunk and can lead to sudden death

Question 30

what is thrombophilia?

Answer 30

a term to describe people who have an increased tendency to form blood clots

Question 31

what can cause underactive inhibition in hereditary thrombophilia?

Answer 31

Antithrombin deficiency
protein C deficiency
Protein S deficiency

Question 32

what are examples of acquired thrombophilia?

Answer 32

Antiphospholipid syndrome
Myeloproliferactive disorders
Malignancy

Question 33

What are examples of hereditary thrombophilia due to overactive coagulation?

Answer 33

• factor V leiden
• prothrombin mutation
• dysfibrinogenaemia
• raised F VIII
• raised FIX

Question 34

what are acquired risk factors for a venous thrombosis?

Answer 34

• age
• immobility
• past history
• obesity
• sepsis
• oestrogen therapy
• pregnancy
• malignancy
• paroxysmal nocturnal haemoglobinuria
• behcets disease

Question 35

what is the problem of a factor V leiden mutation?

Answer 35

Normally protein C prevents blood clots growing large by inactivating factor V.
in the mutation protein C can’t inactivate factor V

Question 36

what is the main risk of having a factor V leiden mutation?

Answer 36

increased risk of clotting

Question 37

what gene is mutated in factor V leiden?

Answer 37

F5

Question 38

why does taking the combined oral contraceptive pill lead to increased thrombosis risk?

Answer 38

Increase in resistance to activated protein C

reduction in protein S levels

reduction in antithrombin

Question 39

what is cancer more likely to lead to thrombus development due to stasis?

Answer 39

prolonged bed rest

extrinsic compression of vessels by the cancer

Question 40

what is cancer more likely to lead to thrombus development due to endothelial injury?

Answer 40

Direct invasion by a cancer
prolonged catheter use
cytotoxics causing endothelial damage
tumour cytokines affecting the vascular endothelium.

Question 41

what is cancer more likely to lead to thrombus development due to causing a hypercoagulable state?

Answer 41

• Activated of the coagulation cascade
• thrombocytosis
• enhanced platelet activation
• suppression of fibrinolysis

Question 42

what is there enhanced platelet activation in cancer?

Answer 42

upregulation of PF4,CD62,CD63

Question 43

What are the effects of chronic venous insufficiency?

Answer 43

• atrophic changes
• hyperpigmentation
• ulceration
• infection

Question 44

what are possible treatment for venous thrombosis?

Answer 44

Anticoagulants;
- heparin
- warfarin
- DOAC
Local thrombolysis
thrombectomy
ICV filters

Question 45

what are genetic risk factors for arterial thrombosis?

Answer 45

male
family history
elevated FVII
elevated fibrinogen 
hyperhomocystinaemia
low folate

Question 46

what are possible medical treatments for an arterial thrombosis?

Answer 46

antiplatelet agents
heparin
thrombolysis
oral anticoagulation

Question 47

what are possible surgery treatments for an arterial thrombosis?

Answer 47

angioplasty
bypass grafts
endartectomy
diseased valve replacement
enbolectomy
amputation