Clotting

Question 1

First platelets adhere to the site of injury, how so?

Answer 1

Glycoproteins:
Gp 1a/2a + 6 bind directly to exposed collagen
GP 1b bind to vWF, indirectly to collagen
GP 2b/3a bind to Fibrinogen

Question 2

second thrombosis is activated in the platelets by?

Answer 2

Cell surface receptors (ADP, adrenaline, thrombin) activate the conversion of arachidonic acid to Thromboxane 2 by COX

Question 3

Third, What causes platelets to aggregate?

Answer 3

Thromboxane A2

Question 4

After a platelet plug is formed, we then form a fibrin clot. What causes this?

Answer 4

Activation of coagulation Factors by physiological activator e.g. Tissue Factor

These activate eachother in a cascade like dominos

Question 5

What are the final steps in the coagulation cascade

Answer 5

Prothrombin cleaved to Thrombin

Its then cleaves Fibrinogen to Fibrin which forms the clot

Question 6

What natural Anticoagulants keep us from clotting outside sites of injury?

Answer 6

TFPI - switches off clotting factors 7 & 10

Proteins C & S - Switch off 5 & 8

Anti-thrombin - Switches of 5, 8 , 9, 10, 11 & thrombin

Question 7

What triggers fibrinolysis?

Answer 7

Endothelial cells releaseing plasminogen activators (t-PA & u-PA)

Question 8

What do Tissue Plasminogen Activators do?

Answer 8

They cleave plasminogen into plasmin –> breaks down fibrin –> Fibrin Degradation Products

Question 9

what do we test for in a D-dimer?

Answer 9

Fibrin Degradation Products

Question 10

Anti-thrombotic drugs include antiplatelets and anticoagulants. What types of antiplatelets do we have?

Answer 10

• Target adhering Gylcoproteins (Abciximab)
• Target surface receptors (Clopidogrel & Ticagrelor)
• Target Thromboxane 2 production (Aspirin)

Question 11

Warfarin is a common anti-coagulant what does it do?

Answer 11

Reduces conc of various clotting factors inc 2, 7, 9, 10 & prothrombin
works by inhibiting Vit K

Question 12

Other anti-coagulants include heparins and DOACs, what do DOACs do?

Answer 12

Direct Oral AntiCoagulants:

1) Rivaroxaban targets activated factor 10
2) Dabigatran targets thrombin

Question 13

The clotting cascade starts in two different pathways and becomes the common pathway.
Which factors are involved in each pathway?

Answer 13

Intrinsic  = 8, ,9, 11 & 12
Extrinsic = Tissue Factor (TF) & factor 7

They converge on 10

Question 14

What test measures the function of each of the pathways in the clotting cascade?

Answer 14

Prothrombin time (PT) is a test of the extrinsic pathway

activated Partial Thromboplastin Time (aPTT) is a test of the intrinsic pathway

Question 15

Thrombin is a product of the common pathway of clotting, what effect does it have on the intrinsic/extrinsic pathways?

Answer 15

It has a -ve feedback effect on the intrinsic pathway

Question 16

What effect would Warfarin have on the aPTT & PT

Answer 16

could prolong both because it acts on both pathways

Question 17

What effect would aspirin have on the aPTT or PT?

Answer 17

None,

Aspiring inhibits COX enzymes preventing aggregation of platelets so it isn’t involved in the clotting cascade