haemostasis 2

Question 1

Characteristics of Abnormal Bleeding

Answer 1

Characteristics of Abnormal Bleeding Bleeding is abnormal if it is:
§ ‘Spontaneous’
§ Out of proportion to the trauma/injury. Note that ~12% of population have ‘easy bruising’.
§ Unduly prolonged.
§ Restarts after appearing to stop.

Question 2

haemostatic plug formation summary

Answer 2

vessel constriction
formation of an unstable platelet plug
stabilisation of the plug with fibrin
vessel repair and dissolution of clot

Question 3

Defects of Primary Haemostasis Defect:

Answer 3

Defects of Primary Haemostasis Defect:
§ Collagen – Vessel Wall:
o E.G. Steroid Therapy (makes walls weak), age and scurvy.
§ Von Williebrand Factor (VWF):
o Von Williebrand Disease – a genetic deficiency of VWF.
§ Platelets:
o Aspirin and other drugs affect platelet activity.
o Thrombocytopenia is a disease that affects the number of platelets in the bloodstream (presents with petechiae).

Question 4

§ The normal primary haemostatic response:

Answer 4

§ The normal primary haemostatic response:
o Endothelial wall damage à exposed collagen binds to VWF à VWF binding sites exposed and platelets aggregate onto VWF à primary haemostatic plug formation.

Question 5

EXAMPLE: Von Williebrand Disease – VWD

Answer 5

§ VMF Deficiency (VWD) response:
o Endothelial wall damage à platelets can only bind to exposed collagen (in some situations) as no VWF à less aggregation and NO primary platelet plug formation.

Question 6

Defects of Primary Haemostasis: Pattern of Bleeding

Answer 6

The bleeding could be a defect in primary haemostasis if the bleeding is: 
Immediate. 
Easy bruising. 
Nosebleeds (prolonged: >20 minutes). 
Gum bleeding (prolonged). 
Menorrhagia 
Bleeding after trauma/surgery 
Petechiae

Question 7

Defects of Secondary Haemostasis

Answer 7

Defects of Secondary Haemostasis – Generation of thrombin. Defect in the fibrin mesh formation:
§ Thrombin converts fibrinogen to fibrin which forms the insoluble mesh around the platelets to stabilise them.

Question 8

Thrombin Generation by the Coagulation Cascade

Answer 8

Thrombin Generation by the Coagulation Cascade This thrombogram visualises the process of coagulation.
§ The lag time after the TF (tissue factor) trigger due to the time taken to generate the cofactors and anticoagulant enzymes before the burst of thrombin.
§ In haemophilia, F8 is missing which causes a failure in thrombin burst leads to slower and lower increase in thrombin à clot does not stabilise.

Question 9

EXAMPLE: Haemophilia –

Answer 9

EXAMPLE: Haemophilia – Haemarthrosis is a hallmark!
§ The normal fibrin clot formation mechanism:
o Thrombin is formed from generates fibrin from fibrinogen à fibrin crosslinks via F13a (mediated by thrombin) à stable clot forms.
§ Haemophilia response mechanism:
o Deficiency in F8 or F9 causes a lack of thrombin to be produced à less fibrinogen to fibrin so less fibrin à less crosslinking as less F13a produced via thrombin.

Question 10

Causes of Defects in Secondary Haemostasis:

Answer 10

Causes of Defects in Secondary Haemostasis: Deficiency or defect of coagulation factors. The bleeding could be due to a defect in secondary haemostasis from:
§ Genetic examples – Haemophilia: F8 or F9 deficiency.
§ Liver disease – Most coagulation factors made in liver.
§ Drugs – Warfarin: inhibits synthesis of factors.
§ Dilution – Results from volume replacement.
Consumption – Disseminated Intravascular Coagulation (acquired).