Lecture 6: Normal Haemostasis

Question 1

What is haemostasis?

Answer 1

How blood clots

Question 2

What is thrombosis?

Answer 2

Abnormal formation of blood clots

Question 3

What forms a blood clot?

Answer 3

A fibrin mesh which attaches to the phospholipid membrane of platelets and surrounds the blood cells like a net.

Question 4

What is factor IIa (2a) also known as?

Answer 4

Thrombin

Question 5

What is the extrinsic pathway also known as?

Answer 5

The tissue factor pathway

Question 6

What are the important components of the extrinsic pathway?

Answer 6

Factor VIIa binding to tissue factor and activating factor X to Xa, which in turn activates factor II to convert fibrinogen to fibrin.

Question 7

What is the function of thrombin?

Answer 7

Converts fibrinogen to fibrin

Question 8

What is the intrinsic pathway?

Answer 8

Also known as the contact activation pathway and involve a longer activation cascade.

Question 9

What is the common pathway?

Answer 9

After activation of one of the other pathways, it maintains the coagulation cascade by making tenase which creates more factor X to continue the reaction. This a slower reaction but maintains the pathway.

Question 10

Why can this waterfall theory not properly explain haemostasis?

Answer 10

Deficiencies in different factors either result in no bleeding (FXII) or abnormal bleeding (FVII) even though they are both necessary to start one of the cascades.

Question 11

What are the series of steps that lead to coagulation in the cell-based model?

Answer 11

Initiation, amplification, propagation, termination

Question 12

What enzymes are involved in the coagulation cascade and what is their function?

Answer 12

Extrinsic tenase- FVIIa and TF bind to make the enzyme and cleave FX to Xa. Intrinsic tenase- FVIIIa and IXa also cleave FX. Prothrombinase- cleaves FII to FIIa (thrombin)

Question 13

How does FVIIIa help FIXa to activate FX?

Answer 13

FIXa and X curve round FVIIIa to interact with each other.

Question 14

What happens if there is a mutation in FVIII?

Answer 14

Mild haemophilia because factor IXa and X can’t curve round FVIIIa properly.

Question 15

What is EMICIZUMAB?

Answer 15

A humanised antibody which mimics the function of FVIIIa

Question 16

What are the natural inhibitors of the coagulation cascade?

Answer 16

Tissue factor pathway inhibitor, antithrombin and protein C pathway

Question 17

How is coagulation measured in a lab?

Answer 17

Prothrombin time (in secs), activated partial thromboplastin time (APTT) (in secs), fibrinogen ( in g/L)

Question 18

What is haemophilia A?

Answer 18

An X-linked disorder affecting factor VIII, can’t form clots properly, can be different levels of severity. Can cause spontaneous bleed which can cause joint deformities and muscle weakness.

Question 19

What are the two different types of thrombosis?

Answer 19

Venous e.g. deep vein thrombosis or arterial e.g. myocardial infarction

Question 20

What is disseminated intravascular coagulation (DIC)?

Answer 20

An intravascular activation of coagulation (thrombin explosion) causing widespread deposition of fibrin in the circulation. Leads to inadequate blood supply and organ failure.

Question 21

What lab results indicate DIC?

Answer 21

Prolonged PT and APTT, low fibrinogen levels, low platelet count