Haemostasis

Question 1

What is haemostasis?

What does the normal haemostatic response involve?

Answer 1

• the process that results in the stopping of bleeding following blood vessel injury
• complex interactions between activated clotting factors and platelets at the site of blood vessel injury

Question 2

What is the sequence of events following blood vessel injury?

Answer 2

• Localised vasoconstriction at the sit of injury
  1. Platelet adhesion to sub endothelium of damaged blood vessel
  Platelet aggregation and activation
  2. Activation of coagulation cascade
  Fibrin formation
• Thrombus Formation
• Fibrinolytic degradation of clot / blood vessel repair

Question 3

What are the two glycoprotein receptors incorporated into the lipid bilayer of platelets?

Answer 3

GPIb and GPIIb/IIIa

Question 4

What allows platelets to change shape?

Answer 4

actin and myosin fibrils which interact upon platelet activation

Question 5

What are the 3 types of storage granules found in platelets? What are their purposes?

Answer 5

dense - mediators of activation including serotonin, ADP, catecholamines and calcium
alpha - contain clotting factors V, VIII, fibrinogen, VWF and other substances including platelet factor 4 and platelet-derived growth factor
glycogen - provide the energy source for platelet reactions

Question 6

Draw the coagulation cascade

Answer 6

see booklet

Question 7

Describe the role of platelets in the haemostatic response

Answer 7

• transient localised vasoconstricción –> platelets form a mechanical plug
• platelets adhere to exposed sub-endothelial collagen
• vWF adheres GP1b
• GPIIb/IIIa upgraded to membrane, binds to vWF and allows aggregation
• ADP is released from damaged blood vessel endothelial cells
• ADP and exposed collagen and thrombin activates platelets and they release aloha and dense granules

Question 8

What are the bleeding tendency disorders and what causes them?

Answer 8

• Bernard-Soulier sundrome = deficiency of GPIb
• Glanzmann;s Thrombasthenia = deficiency of GPIIb/IIIa
• Haemophilia A - factor 8
• Haemophilia B - factor 9
• vWF deficiency
• autoimmune acquired thrombocytopenia
• vitamin K deficient

Question 9

What factors are synthesised from vitamin K?

Answer 9

• 7, 9, 10

Question 10

Describe the fibronolytic response and blood vessel repair

Answer 10

• tPa released from intact endothelial cells
• attaches to fibrin clot
• enables binding of plasminogen
• converted to plasmin
• proteolytic dissolution of clot
• degradation products removed by reticulo-endothelial system
• blood vessel repair occurs simultaneously
• smooth muscle of blood vessels and endothelial cells undergo mitosis - under control of PDGF

Question 11

What are the 3 anticoagulant mechanisms?

Answer 11

• antithrombin
• protein C
• natural heparins

Question 12

What does antithrombin do?

Answer 12

• inactivated thrombin and factor 9. 10, 11

Question 13

• Where in the circulation is the protein C system most important?
• What does protein C do?

Answer 13

• venous side
• in the vicinity of clot formation, free thrombin binds to thrombomodulin
• enables binding of Protein C and thrombin activates it
• activates protein C complexes with protein S and inactive FV, and enzymatically degrades factor 5 and 8
• suppression of coagulation factors and restricts the thrombus to the site of injury

Question 14

What do natural heparins do?

Answer 14

• operate at the level of the blood vessel endothelium
• present on endothelial surface which bind to and enhance the anticoagulant activity of anti-thrombin and the synthesis and relays of platelet inhibitory prostaglandin called prostacyclin

Question 15

Give examples of causes of acquired thrombophilia states

Answer 15

• myeloproliferative disorders
• malignancy
• lupus anticoagulant
• surgery
• long haul flights
• prolonged periods of immobility
• pregnancy
• smoking

Question 16

Give examples of hereditary thrombophilia states

Answer 16

• Factor V leiden mutation, factor V has impaired protein C cofactor activist and is resistant to neutralisation
• protein C, S and AT deficiencies
• mutation of prothrombin gene –> increased prothrombin levels
• hyperhomocysteinaemia

Question 17

What routine tests are used to investigate the clotting cascade?

Answer 17

• platelet count
• prothrombin time
• activate partial thromboplastin time (APTT)
• fibrinogen level
• von Willebrand Factor levels
• platelet aggregation studies

Question 18

What are the two most common test requested?

Answer 18

• prothrombin time (PT)

- activated partial thromboplastin time (APTT)

Question 19

What does an prolonged prothrombin time indicate?

What are the possible causes?

Answer 19

- factor 7 deficiency 
Causes:
- hereditary factor 7 deficiency 
- mild liver disease 
- mild VitK deficiency

Question 20

What does an prolonged APTT indicate?

Answer 20

• requires further testing
• repeat, with mixing test
• if clotting time return to normal –> 8, 9, 11, 12 deficiency
• if clotting time fails to correct –> inhibitor present such as lupus anticoagulant or F8 antibodies

Question 21

What does a prolonged prothrombin and APTT indicate?

Answer 21

• a single factor deficiency in the ‘common pathway’
  e. g. 10, 5, prothrombin, or fibrinogen
• of multiple factor deficiencies due to liver disease, VitK deficiency, warfarin therapy, DIC, dilutional coagulopathy