Thrombosis

Question 1

What’s thrombosis?

Answer 1

Solid mass of blood formed within the CVS involving interaction of endothelial cells, platelets, coagulation cascade which impedes blood flow

Question 2

Features of arterial thrombosis?

Answer 2

Result from atheroma rupture (MI, stroke)
Platelet-rich “white” thrombosis
Block downstream arteries

Question 3

Features of venous thrombosis?

Answer 3

Result from stasis or hypercoagulant state
Platelet-poor “red” thrombus
May move to lungs

Question 4

What makes a blood clot?

Answer 4

Endothelium
Platelets
Coagulation
Fibrinolysis

Question 5

What’s normal haemostasis?

Answer 5

state of equilibrium

fibrinolytic factors, anticoagulant proteins vs coagulation factors, platelets

Question 6

Describe process of haemostasis

Answer 6

• response to injury –> vessel constriction
• formation of unstable platelet plug : platelet adhesion + aggregation
• fibrin stabilises plug : blood coagulation
• fibrinolysis : dissolution of clot + vessel repair

Question 7

What does development of a thrombus depend on?

Answer 7

Changes in normal blood flow
Alterations in blood constituents
Damage to endothelial layer

Question 8

Risk factors of endothelial dysfunction?

Answer 8

smoking + hypertension

Question 9

Risk factors of endothelial damage?

Answer 9

surgery, catheter (PICC lines), trauma

Question 10

eg of hereditary factors of hypercoagulability?

Answer 10

factor V Leiden, prothrombin G20210A, protein C + S deficiency

Question 11

eg of acquired factors of hypercoagulability?

Answer 11

cancer, chemo, oral contraceptive/hormone replacement therapy, pregnancy, obesity, HIT

Question 12

Risk factors of stasis?

Answer 12

immobility, stroke, cardiac failure, pelvic obstruction, dehydration, hyperviscosity, polycythemia –> endothelial injury

Question 13

What’s Virchow’s Triad?

Answer 13

endothelial damage
hypercoagulability
stasis

Question 14

Mechanism when endothelial damage?

Answer 14

1º
-collagen + vWF binds, activates platelets
-platelets enlarge + release granule contents
-exposing phospholipid surface + express receptors
-TF + collagen initiate coagulation cascade
2º
-activated platelet + fibrin form mesh

Question 15

Describe the fibrinolytic system

Answer 15

• endothelial cells release tPA
• tPA activates plasminogen
• plasminogen -> plasmin
• plasmin breaks up clot
• forming fibrin fragments + D-dimers

Question 16

What’s PL?

Answer 16

charged phospholipids on platelet surface for coagulation

Question 17

Describe the cell based model of coagulation

Answer 17

• damaged tissue releases TF
• TF activates 7a
• 7a initiates thrombin required for amplification
• 8a + 9a on platelet surface activates 10a
• 10a has cofactor 5a
• 10a + 5a induces prothrombin
• prothrombin -> thrombin
• thrombin induces fibrinogen -> fibrin

Question 18

What’s initiation of cell based model of coagulation?

Answer 18

TF released with 7a activating thrombin

Question 19

What’s amplification of cell based model of coagulation?

Answer 19

generating more thrombin

9a + 8a on platelet activates 10a

Question 20

What’s propagation of cell based model of coagulation?

Answer 20

10a + 5a propagate more induction of thrombin

Question 21

What’s the common pathway of coagulation?

Answer 21

• 10a with cofactors: 5a, PL, Ca2+ on platelet surface
• 10a activates prothrombin -> thrombin
• thrombin activates fibrinogen -> fibrin

Question 22

What’s the extrinsic pathway of coagulation?

Answer 22

• tissue damage activates TF

- TF, 7a, Ca2+ activates 10 -> 10a

Question 23

What’s the intrinsic pathway of coagulation?

Answer 23

• 12 -> 12a
• 12a activates 11 -> 11a
• 11a activates 9 -> 9a
• 9a with cofactors: 8a, PL, Ca2+
• 9a activates 10 -> 10a
• 10a activates prothrombin -> thrombin

Question 24

How’s 10 activated?

Answer 24

EXTRINSIC : TF, 7a, Ca2+ activates 10 -> 10a

INSTRINSIC : 9a with cofactors: 8a, PL, Ca2+ activates 10 -> 10a

Question 25

What's activated protein C (APC)?

Answer 25

formed from protein C + S | inhibits 8a + 5a -less amplification

Question 26

What's antithrombin III?

Answer 26

inhibit 10 + thrombin

Question 27

What are the natural coagulation inhibitors?

Answer 27

activated protein C (APC), antithrombin III

Question 28

What's antithrombin III deficiency?

Answer 28

factor 5 Leiden - mutation in 5, which is resistant to APC so induces clotting

Question 29

Why's there increased risk of stasis at valves?

Answer 29

blood eddy around valves

Question 30

Where is the riskier DVT?

Answer 30

above knee increases risk of PE

Question 31

What's the annual incidence DVT?

Answer 31

1:1000

Question 32

What's inherited thrombophilia?

Answer 32

8:100

Question 33

Clinical features of DVT?

Answer 33

pain, tenderness of veins, limb swelling, superficial venous distension, increased skin temp, discoloration due to obstruction to the venous drainage

Question 34

What are anticoagulants + eg?

Answer 34

prevent | warfarin, heparin, direct oral anticoagulants

Question 35

What are 'clot busters' + eg?

Answer 35

reverse | plasminogen activators, streptokinase

Question 36

What are the bleeding complications from anticoagulants?

Answer 36

👁, bruising, intracerebral bleeding