Intro the heritable bleeding disorders (Haematology pathology)

Question 1

Describe the mechanism of haemostatic plug formation

Answer 1

1) Rupture to the blood vessel wall
2) platelets adhere to site of vascular injury by sticking to Von Willebrand factor.
3) Platelets get activated and stick to each other forming a platelet plug.
4) Positive feedback loop, platelets activate other platelets.
5) Platelets activate the formation of a fibrin clot with stabilises the platelet plug.

Question 2

Where does synthesis of thromboxin occur and what is the action of thromboxin?

Answer 2

Thomboxin is synthesised inside the platelet and it activates the platelet.

Question 3

Describe the Extrinsic part of the coagulation cascade?

Answer 3

1) The extrinsic system is activated when tissue factor is exposed during damage.
2) Tissue factor activates factor 7 to factor 7a.
3) Factor 7a converts F10 to F10a
4) F10a along with a co-factor enzymatically cleaves prothrombin to form thrombin.
5) thrombin converts fibrinogen into fibrin which forms the clot.

Question 4

Describe the intrinsic part of the coagulation cascade?

Answer 4

1) The intrinsic system does not require activation from mediators that are outside the blood.
2) F12&raquo_space;F12a
3) F12a cleaves F11»>F11a
4) F11a cleaves F9&raquo_space;> F9a
5) F9a along with a cofactor actives F10 to F10a
6) F10a along with a cofactor cleaves prothrombin into thrombin.
7) thrombin converts fibrinogen into fibrin which forms the clot.

Question 5

What is the role of protein C in the coagulation?

Answer 5

Protein C (along with its co-factor Protein S) is an anti-coagulant.

Question 6

What is the role of plasmin and how is it formed?

Answer 6

Plasmin is the enzyme that breaks down fibrin. Plasmin is generated by the cleavage of plasminogen. This occurs inside the clot.

Question 7

How are bleeding disorders categorised?

Answer 7

1) Congenital or Acquired

2) Primary Haemostasis (platelets, vessel wall, von willebrand) Or Coagulation cascade defect.

Question 8

Mucosal and bleeding into the skin is characteristic of what type disorder?

Answer 8

Platelet disorder

Question 9

Deep muscular and joint bleeds are characteristc of what type of disorder?

Answer 9

Coagulation defect

Question 10

What are the characteristics of platelet / vessel wall defects?

Answer 10

1) reduced number of platelets
2) Abnormal platelet function
3) Abnormal vessel wall
4) Abnormal interaction between platelets and vessel wall

Question 11

What are some of the symptoms of coagulation defects?

Answer 11

• Deep spread haematoma
• Haemarthrosis
• Retroperitoneal bleeding
• Bleeding prolonged and often recurrent

Question 12

What is Petechiae a sign of?

Answer 12

Petechiae is a skin condition caused by vascular / platelet defects

Question 13

How is von willebrand disease inherited?

Answer 13

Type 1 and Type 2 = autosommal dominant

Type 3 = recessive

Question 14

What are the different types of von willebrand disease?

Answer 14

Type 1 - is most common and is due to reduced amount of normal von willebrand factor

Type 2 - normal amount of abnormal von willebrand factor.

Type 3 - (rare) Von willebrand is absent

Question 15

What is the role of von willebrand factor?

Answer 15

VWF helps the platelets adhere to the injured vessel wall.

Question 16

How is factor 8 carried in the blood?

Answer 16

Von willebrand factor acts as a carrier protein for factor 8. It allows factor 8 to remain in the circulation.

Question 17

Deficiency in what factors will give a long partial thromboplastin time?

Answer 17

Deficiency in factor 8 / factor 9 will have a long partial thromboplastin time as it is part of the intrinsic pathway.

Question 18

How is Haemophilia A / B inherited?

Answer 18

X linked recessive

females act as carriers but males are affected

Question 19

What deficiencies cause Haemophilia A / B?

Answer 19

Haemophilia A is caused by Factor 8 deficiency.

Haemophilia B is caused by Factor 9 deficiency.

Question 20

What are the different tests done for the coagulation pathway?

Answer 20

1) Activated partial thromboplastin time (intrinsic pathway)
2) Prothrombin time
3) Thrombin clotting time
4) Euglobulin lysis time