Haemostasis

Question 1

What factors does Haemostasis rely upon being interlinked?

Answer 1

• normal haemostatic response to vascular damage - depends on a closely linked interaction between the blood vessel wall, circulating platelets and blood coagulation factors

Question 2

What is the purpose of clotting?

Answer 2

• efficient and rapid mechanism for stopping bleeding from sites of blood vessel injury - essential for survival

Question 3

Why does the response need to be tightly controlled?

Answer 3

to prevent extensive clots developing

to be able to break down such clots once the damage is repaired

Question 4

What are the five major components of haemostasis?

Answer 4

platelets, coagulation factors, coagulation inhibitors, fibrinolysis and blood vessels

Question 5

Where are platelets formed from? What regulates platelet formation, how long are they around for and what do they do?

Answer 5

• produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes
• They circulate for 7–10 days
• Thrombopoietin (TPO) - the major regulator of platelet formation, 95% is produced by the liver
• The main function of platelets - the formation of mechanical plugs during the haemostatic response to vascular injury

Question 6

Give an overview of the haemostatic plug formation

Answer 6

On image

Question 7

In terms of haemostasis, what is vasoconstriction

Answer 7

• Immediate vasoconstriction of the injured vessel and reflex constriction of adjacent small arteries and arterioles - responsible for an initial slowing of blood flow to the area of injury
• reduced blood flow allows contact activation of platelets and coagulation factors

Question 8

Describe Platelet reactions and primary haemostatic plug formation

Answer 8

• Following a break in the endothelial lining, there is an initial adherence of platelets to exposed connective tissue, mediated by Von Willebrand factor (VWF)
• VWF
involved in shear‐dependent platelet adhesion to the vessel wall and to other platelets (aggregation)
also carries factor VIII
a large glycoprotein, with multimers made up on average of 2–50 dimeric subunits
VWF is synthesized both in endothelial cells and megakaryocytes

Question 9

Describe Platelet reactions and primary haemostatic plug formation part 2

Answer 9

• Additional platelets from the circulating blood are drawn to the area of injury
• continuing platelet aggregation promotes the growth of the haemostatic plug, which soon covers the exposed connective tissue
• unstable primary haemostatic plug produced by these platelet reactions in the 1st minute or so following injury - usu sufficient to provide temporary control of bleeding

Question 10

Describe Stabilization of the platelet plug by fibrin

Answer 10

• Biochemical reactions of coagulation and you get a Coagulation cascade
• Convert soluble fibrinogen into a meshwork of insoluble fibrin
• Tightly regulated orchestration of coagulation factors, cofactors, and inhibitors
=> result in the controlled formation of the pivotal enzyme thrombin which initiates fibrin formation

Question 11

How is blood clotting regulated?

Answer 11

• protective mechanisms - coagulation factor inhibitors, blood flow and fibrinolysis
• 1st inhibitor to act is tissue factor pathway inhibitor (TFPI) –synthesized in endothelial cells and is present in plasma and platelets and accumulates at the site of injury caused by local platelet activation.
• TFPI inhibits Xa and VIIa and tissue factor to limit the main in vivo pathway.
• There is also direct inactivation of thrombin and other serine protease factors by other circulating inhibitors, of which antithrombin is the most potent
• Heparin potentiates its action markedly

Question 12

What is fibrinolysis and what are the two functions?

Answer 12

• the process whereby fibrin is degraded by plasmin
• Main function
o clot limiting mechanism
o repair and healing mechanism

Question 13

What is Thrombosis?

Answer 13

• The pathological process whereby platelets and fibrin interact with the vessel wall to form a haemostatic plug to cause vascular obstruction

Question 14

Why may defective haemostasis occur/ abnormal bleeding?

Answer 14

o A vascular disorder
o Thrombocytopenia or a disorder of platelet function
o Defective blood coagulation
• Simple tests are employed to assess the platelet, vessel wall and coagulation components of haemostasis

Question 15

Describe Screening tests used in the diagnosis of coagulation disorders

Answer 15

• prothrombin time (PT)
o measures factors VII, X, V, prothrombin (II) and fibrinogen
o Tissue thromboplastin (a brain extract) or [synthetic] tissue factor with lipids and calcium is added to citrated plasma
• activated partial thromboplastin time (APTT)
o Measures factors VIII, IX, XI and XII in addition to factors X, V, prothrombin (II) and fibrinogen.
o Three substances – phospholipid, a surface activator (e.g. kaolin) and calcium are added to citrated plasma
• thrombin (clotting) time (TT)
o sensitive to a deficiency of fibrinogen or inhibition of thrombin
o Diluted bovine thrombin is added to citrated plasma

Question 16

What are the principles for clotting tests?

Answer 16

•	Incubate plasma with reagents necessary for coagulation
o	Phospholipid, co-factors
o	Trigger or activator
o	Calcium
•	Measure time taken to form fibrin clot