Bleeding and Thrombosis

Question 1

What is required for blood clotting?

Answer 1

Abnormal surface

Activator

Question 2

How does an abnormal surface trigger platelet adhesion?

Answer 2

Von Willebrand factor
Exposed sub-endothelial collagen
Physiological activator

Question 3

What do platelets have on their surfaces?

Answer 3

Cell surface receptors - molecules released by damaged sites (activation)
Platelet glycoproteins - binding

Question 4

What is the role of platelets in homeostasis?

Answer 4

Adhere
Activation
Aggregation
Phospholipid surface for coagulation

Question 5

What is required for binding to Von Willebrand factor?

Answer 5

Glycoprotein 1b

Question 6

What is needed for a platelet to adhere?

Answer 6

(vWF)

Glycoprotein 1a and 1b

Question 7

What is required for platelets to activate?

Answer 7

ADP
Epinephrine
COX

Question 8

What is required for platelets to aggregate?

Answer 8

Thromboxane A2

Question 9

What is required for platelets to coagulate?

Answer 9

Phospholipid membrane

Scramblase

Question 10

What is the sequence of scab formation?

Answer 10

Primary homeostatic platelet plug

Fibrin formation

Question 11

What is deficient in haemophilia B?

Answer 11

Factor IX

Question 12

What is deficient in haemophilia A?

Answer 12

Factor VIII

Question 13

Outline the blood clotting cascade

Answer 13

Intrinsic + extrinsic = X–> Xa
Prothrombin to Thrombin
Fibrinogen to Fibrin

Question 14

What are the natural anti-coagulants?

Answer 14

TFPI (Xa and VIIa)
Protein C and Protein S
Antithrombin

Question 15

Outline the process of Fibrinolysis

Answer 15

Endothelial cells secrete u/t-PA (plasminogen activator)
Activate plasminogen –> Plasmin
Plasmin breaks down clot

Question 16

How is fibrinolysis inhibited?

Answer 16

Plasminogen inhibitors

Plasmin inhibitors

Question 17

What is required for clot formation?

Answer 17

Platelets
von Willebrand factor
Coagulation factors

Question 18

What is the role of platelets canaliculi?

Answer 18

Allow it to secrete molecules onto its own surface (excretion of alpha and dense granule)

Question 19

What is the role of scramblase?

Answer 19

“flip” phospholipid membrane to the outside surface for adhesion

Question 20

What is necessary for the clotting process to begin in the platelet?

Answer 20

Thrombin
ADP
Epinephrine to contact platelets

Question 21

Aspirin inhibits what to act as an antithrombotic?

Answer 21

COX (cyclo-oxygenase)

conversion of Arachadonic acid to Thromboxane A2

Question 22

How do Clopidogrel/Ticagrelor work?

Answer 22

Prevent activation - Thrombin/ADP/Epinephrine binding to the platelet

Question 23

How does Fibrin reach the site of injury?

Answer 23

Fibrinogen binds to platelets, platelets carry it to the injury to then cleave it

Question 24

What is the intrinsic pathway of clotting?

Answer 24

(extrinsic activates Thrombin)
Thrombin activates XI
XIa converts IX > IXa to form more X > Xa
Xa activates Prothrombin
Thrombin cleaves Fibrinogen > Fibrin

Question 25

What is the extrinsic pathway for clotting?

Answer 25

Factor VII binds to tissue factor to form activate Factor X to Xa Xa activates Prothrombin Thrombin converts Fibrinogen --> Fibrin

Question 26

How does TFPI work?

Answer 26

"deactivates" Factor X and VII

Question 27

How does activated protein C and protein S work?

Answer 27

Deactivates VIII and V

Question 28

How does antithrombin work?

Answer 28

``` Deactivates: Thrombin IX VIII XI X ```

Question 29

What is D-dimer?

Answer 29

Fibrin degradation (breakdown) product

Question 30

How does Warfarin work?

Answer 30

Inhibits vitamin K factors (1972) X, IX, VII, II

Question 31

How do Abciximab/Tirofiban work?

Answer 31

Prevent Glycoprotein IIb/IIIa work | prevents binding of fibrinogen

Question 32

How does heparin work?

Answer 32

Inhibit thrombin and activated Xa

Question 33

How do DOACs Rivaroxaban, Apixaban work?

Answer 33

Stop activated Xa