Blood coagulation: clot formation

Question 1

blood coagulation

Answer 1

transformation of blood into a solid gel called a clot or thrombus

Question 2

what does a clot consist of

Answer 2

mainly of protein polymer fibrin

Question 3

where does clotting occur?

Answer 3

locally around platelet plug

Question 4

function of clotting

Answer 4

support and reinforce platelet plug, solidify remaining blood

Question 5

what occurs at each step of the coagulation cascade?

Answer 5

inactive plasma protein (factor) is converted to a proteolytic enzyme
proteolytic enzyme catalyses the generation of the next enzyme in the sequence
each activation results from splitting of small peptide fragment from the inactive plasma protein precursor - exposes active site of the enzyme

Question 6

what does the cascade of plasma enzyme activations require?

Answer 6

activated platelets, plasma cofactors, calcium ions

Question 7

prothrombin -> thrombin

Answer 7

thrombin catalyses the reaction where several polypeptides are split from molecules of fibrinogen

Question 8

fibrinogen remnants

Answer 8

bind together to form fibrin

Question 9

structure of fibrin

Answer 9

loose mesh of interlacing strands

rapidly stabilised and strengthened by covalent cross-linkages mediated by factor XIIIa enzyme

Question 10

factor XIIIa

Answer 10

formed from factor XIII - reaction catalysed by thrombin

Question 11

thrombin functions

Answer 11

catalyses the formation of loose fibrin
activates factor XIII
positive feedback on its own function: activates cascade proteins and platelets

Question 12

what substances are trapped in the fibrin meshwork?

Answer 12

erythrocytes, other cells

Question 13

when can clotting occur?

Answer 13

in absense of all other substances except platelets

Question 14

why are platelets necessary for clotting?

Answer 14

several cascade reactions take place on surface of platelets

Question 15

what do activated platelets display?

Answer 15

specific plasma membrane receptors that bind clotting factors and allow reactions to happen on their surface
platelet factor (PF) - phospholipid. cofactor in steps mediated by bound clotting factors

Question 16

Ca2+ and clotting

Answer 16

required in several steps.
concentration can never decrease enough to cause clotting defects, as death from muscle paralysis or cardiac arrythmias would occur

Question 17

2 pathways in coagulation cascade

Answer 17

intrinsic - everything it needs is in the blood

extrinsic - cellular element outside of blood is needed

Question 18

first plasma protein in intrinsic pathway and its contact activation

Answer 18

factor XII
activated to factor XIIa when contacting substances e.g collagen fibres
requires plasma proteins

Question 19

factor XIIa function

Answer 19

catalyses activation of XI to XIa

Question 20

factor XIa function

Answer 20

catalyses activation of IX to factor IXa

Question 21

factor IXa function

Answer 21

activates X to factor Xa

also mediated by factor VIIIa (cofactor, not enzyme)

Question 22

factor Xa function

Answer 22

enzyme that converts prothrombin to thrombin

Question 23

haemophilia and factors

Answer 23

excessive bleeding
usually due to genetic absence of factor VIII
sometimes due to absence of factor IX

Question 24

what does extrinsic pathway begin with?

Answer 24

protein called: tissue factor - not plasma protein
found on outer plasma membrane of various tissue cells, including fibroblasts and cells in walls of vessels outside endothelium

Question 25

tissue factor function

Answer 25

binds plasma protein - factor VII - activated to factor VIIa

Question 26

factor VIIa functions

Answer 26

catalyses activation of factor X to Xa and IX to IXa (more factor X via intrinsic pathway)

Question 27

merging of intrinsic and extrinsic pathways

Answer 27

merge at factor Xa - catalyses conversion of prothrombin to thrombin - catalyses formation of fibrin

Question 28

thrombin and factors

Answer 28

activationof XI and VIII in intrinsic pathwat, V.

Question 29

use and importance of intrinsic vs extrinsic factors

Answer 29

extrinsic pathway initiates clotting factor XII plays little role amount of thrombin generated by extrinsic pathway is too small to to produce adequate, sustained coagulation extrinsic pathway triggers thrombin's positive feedback mechanisms on the intrinsic pathway - activation of factors V, VIII and XI and platelets -triggers intrinsic pathway w/out XII thrombin recruits intrinsic pathway and facilitates prothrombin-thrombin step by activating factor V and platelets

Question 30

official designations for clotting factors and synonyms more commonly used

Answer 30

``` Factor I (fibrinogen) Factor Ia (fibrin) Factor II (prothrombin) Factor IIa (thrombin) Factor III (tissue factor, tissue thromboplastin) Factor IV (Ca2+) Factors V, VII, VIII, IX, X, XI, XII, XIII (inactive forms of factors) platelet factor (PF) ```

Question 31

liver's role in coagulation cascade

Answer 31

liver disease - bleeding problems produces many plasma clotting factors produces bile salts, important for normal intestinal absorption of vitamin K liver requires vitamin K to produce prothrombin and other factors