2ary Haemostasis

Question 1

What is goal of 2ary haemostasis?

Answer 1

Produce a fibrin clot network

Question 2

What is the coagulation cascade driven by?

Answer 2

By coagulation factors which normally circulate in the plasma as inactive proenzyme

Question 3

What is the final product of coagulation cascade?

Answer 3

Conversion of fibrinogen to fibrin by thrombin. Fibrin polymerises and forms a network

Question 4

What are the pathways involved in coagulation?

Answer 4

Intrinsic, extrinsic, common

Question 5

What is the extrinsic pathway triggered by?

Answer 5

Injury - tissue factor is exposed to the blood

Question 6

Where is tissue factor produced?

Answer 6

On the cell membrane of the perivascular cells (SMCs, fibroblasts)

Question 7

Describe extrinsic pathway

Answer 7

1. TF binds to XII from the blood and activates it, forming XIIa on surface of platelet
2. X can also bind to TF-VIIa complex, activating it to F10a (amplification of response)

Question 8

Describe the common pathway

Answer 8

1. Xa converts prothrombin (II) into thrombin (IIa)
2. Thrombin (IIa) converts the soluble molecule fibrinogen (I) into fibrin (Ia)
3. Fibrin (Ia) is converted into cross-linking fibrin

Question 9

What factor is prothrombin?

Answer 9

Factor II (F2)

Question 10

What factor is fibrinogen?

Answer 10

Factor I (F1)

Question 11

What is purpose of FXIIIa

Answer 11

Acts as superglue, making more reactions between fibrin sheets

Question 12

What is intrinsic pathway triggered by?

Answer 12

Negatively charged surfaces e.g. glass, collagen, polyphosphates

Question 13

What are steps in intrinsic pathway?

Answer 13

Injury to blood vessel

1. XII –> XIIa
2. XIIa converts XI –> XIa
3. XIa converts IX into IXa
4. IXa converts X –> Xa (with help of VIIIa)

Question 14

Why is Vitamin K essential for coagulation?

Answer 14

Is a cofactor for an enzyme that allows the maturation of coagulation factors

Question 15

What is the extrinsic pathway activated by?

Answer 15

External trauma that causes blood to escape from the vascular system. This pathway is quicker than the intrinsic pathway. It involves factor VII.

Question 16

What is the intrinsic pathway activated by?

Answer 16

Trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen. This pathway is slower than the extrinsic pathway, but more important. It involves factors XII, XI, IX, VIII.

Question 17

What is VIII (FVIII)?

Answer 17

An essential blood clotting protein which circulates in the bloodstream in an inactive form, bound to another vWf, until an injury that damages blood vessels occurs.

Question 18

What is FVIII response to injury?

Answer 18

Is activated and separates from vWf, becoming VIIIa

Question 19

What is role of VIIIa?

Answer 19

Is a cofactor for factor IXa, which, in the presence of Ca2+ and phospholipids, forms a complex that converts factor X to the activated form Xa.

Question 20

What are people with high levels of VIII at risk of?

Answer 20

Pulmonary embolism and DVT

Question 21

What is role of FXIII?

Answer 21

Stabilises fibrin clot –> activated to XIIIa

Question 22

What is role of FV?

Answer 22

Essential cofactor in coagulation cascade

Activated to Va and helps Xa convert prothrombin to thrombin

Question 23

What is Factor 5 Leiden?

Answer 23

Mutation in FV which causes an increase in blood clotting (hypercoagulability)