Pathophysiology of Haemostasis and coagulation

Question 1

what is clotting/coagulation?

Answer 1

the formation of a thrombus/clot which can occur before and after death

Question 2

what is the final product of coagulation?

Answer 2

a platelet fibrin thrombus

Question 3

what is haemostasis?

Answer 3

the process of repairing damaged blood vessels to maintain their integrity to keep blood within the vessel.

Question 4

what is primary haemostasis?

Answer 4

• mediated by platelets

- platelets adhere together forming a weak ‘platelet plug’

Question 5

what is secondary haemostasis?

Answer 5

a coagulation cascade occurs stabilising the platelet plug

Question 6

what happens when there’s disruption to endothelial cells?

Answer 6

1. transient vasoconstriction of the endothelial cells
   - this is mediated by neural stimulation and release of endothelin from endothelial cells in response to thrombin and shearing forces.
2. von Willebrand Factors bind to the exposed collagen on the basement membrane via GPIb found on platelets. This is called ADHESION which causes the platelets to change shape.
3. platelets degranulate RELEASING ADP and TXA2 and Ca
4. ADP induces the expression of GP2b and GP3a for AGGREGATION, and the expression of fibrinogen(FNG) as a linker molecule.
5. TXA2 promotes platelet AGGREGATION by enhancing linking b/w FNG and GP2b/GP3a

Question 7

what lab tests are carried out for primary haemostatic disorders?

Answer 7

1. platelet count (quantitative)
2. blood smear (qualitative)
3. bone marrow biopsy (as the precursors of platelets-megakaryocytes-are in bone marrows)
4. test for VWF (von Willebrand Factor) levels

Question 8

what is the aim of the coagulation cascade in the secondary haemostasis action?

Answer 8

• to stabilise the weak platelet plug by generating thrombin converting the platelet linker molecule (fibrinogen) into cross linked fibrin.
• this forms platelet fibrin thrombus

Question 9

where are most coagulant factors and inhibitors synthesised?

Answer 9

in the liver

Question 10

what is required for clotting factors 2, 7, 9 and 10 to work?

Answer 10

vitamin K

Question 11

what three things are required to carry out the secondary haemostasis coagulation cascade?

Answer 11

1. exposure of activating substance i.e. tissue factor (factor 7)
2. phospholipid surface of platelets
3. calcium from dense core of granules of platelets

Question 12

what systems is the coagulation cascade divided into?

Answer 12

1. extrinsic

2. intrinsic

Question 13

what coagulation factors are required in the extrinsic system?

Answer 13

factor 7

Question 14

what coagulation factors are required in the intrinsic system?

Answer 14

factors 8,9,11,12

Question 15

what coagulation factors are required in the final common pathway?

Answer 15

factors 1, 2, 5 and 10

Question 16

what coagulation factor is used to cause the cross-link of fibrin monomers?

Answer 16

factor 13

Question 17

what is the function of thrombin?

Answer 17

• makes fibrin monomers from fibrinogen

- also activates the fibrin stabilising factor 13 to strengthen the fibrin clot

Question 18

what switches off thrombin?

Answer 18

• the anticoagulant ‘antithrombin3’

- this limits clot formation where appropriate

Question 19

what factors does antithrombin3 inactivate?

Answer 19

factors 10a, 9a, 11a, 12a and 7a

Question 20

what is tissue plasminogen activator?

Answer 20

a protein found on endothelial cells which activates plasminogen to form plasmin
-used to breakdown a clot

Question 21

what is the role of plasmin?

Answer 21

• it cleaves fibrin and fibrinogen into fibrinogen degradation products (FDPs).
• blocks platelet aggregation

Question 22

what is used to inactivate plasmin?

Answer 22

alpha2-antiplasmin

Question 23

what does the clotting test for prothrombin time (PT) evaluate?

Answer 23

the extrinsic coagulation system (plus final common pathway) down to the formation of the fibrin clot - factors that are evaluated are 7, 10, 5, 2, 1

Question 24

what is the normal prothrombin time?

Answer 24

11 to 15 seconds

Question 25

what is the prothrombin time used for?

Answer 25

1. monitor people taking warfarin for anticoagulation
2. evaluate liver function (if PT is increased, can mean liver disease etc)
3. used to detect factor 7 deficiency if aPTT is normal

Question 26

what does the activated partial thromboplastin time evaluate?

Answer 26

the intrinsic coagulation system down to formation of a fibrin clot.
-Factors that are evaluated include 1, 2, 5, 9, 8, 10, 11, 12 (basically not 7)

Question 27

what is the normal activated partial thromboplastin time?

Answer 27

30 to 40 seconds

Question 28

what is the use of activated partial thromboplastin time?

Answer 28

1. to monitor heparin anticoagulation therapy. (Heparin enhances antithrombin III activity)
2. to detect factor deficiencies in the intrinsic system if the PT is normal.