Haemostasis

Question 1

What are the principles of haemostasis?

Answer 1

To prevent bleeding and unnecessary coagulation, allowing blood to flow

Question 2

What things are essential for haemostasis?

Answer 2

1) To keep blood moving
2) Platelets
3) Coagulation factors
4) Anticoagulant factors

Question 3

What are the precursors to platelets?

Answer 3

Megakaryocytes

Question 4

What is the normal platelet count?

Answer 4

150-400 x 109/L

Question 5

What is the normal life span of platelets?

Answer 5

7-10 days

Question 6

What are the three major steps of haemostasis?

Answer 6

1) Vasoconstriction
2) Temporary blockage of a break by a platelet plug
3) Blood coagulation, formationof a fibrin clot which stabilises the friable platelet plug into a stable clot

Question 7

What is the end result of the activation of the clotting system?

Answer 7

Production of thrombin which acts on fibrinogen to produce fibrin filaments, which are then deposited and trap red blood cells

Question 8

What are the only cells that can be in contact with blood and not clot it?

Answer 8

Endothelial cells, white blood cells, unactivated platelets and red blood cells

Question 9

What are platelets activated by?

Answer 9

Collagen surfaces, ADP (released by activated platelets for amplication purposes), thromboxane A2 and thrombin

Question 10

What do platelets do when they are activated?

Answer 10

1) Stick to the exposed subendothelium, specifically to von Willebrand factor which is concentrated on the subendothelial basement membrane
2) Aggregate with other platelets to form a plug (fibrinogen binds to the platelets and sticks them together)
3) Swell and change shape into sticky spheres
4) Secrete factors from platelet granules that help the platelet plug to grow and aid clotting

Question 11

How does aspirin decrease platelet aggregation?

Answer 11

Irreversibly inactivates cyclooxygenase - one of the enzymes responsible for the production of thomboxane A2

Question 12

What is the endpoint of the clotting cascade?

Answer 12

Fibrin is produced

Question 13

What is the enzyme that cleaves the circulating plasma protein fibrinogen into fibrin?

Answer 13

Thrombin

Question 14

What do many of the clotting factors (including Factors II, VII, IX and X) require for their synthesis?

Answer 14

Vitamin K

Question 15

What are some examples of co-factors for the enzymes of the clotting cascade?

Answer 15

Phospholipids and calcium

Question 16

What are the two clotting pathways?

Answer 16

Intrinsic (factors all contained within blood, triggered by negatively charged surface, no vessel needs to be broken for it to occur)

Extrinsic (needs a tissue factor - thromboplastin. Triggered by thromboplastin released from damaged cells adjacent to the area of haemorrhage)

Question 17

What is the role of the vascular wall in clotting?

Answer 17

Arterial media contracts when an artery is damaged

Subendothelium traps platelets

Endothelium secrete substances such as tissue plasminogen activaator, thrombomodulin, vwf, tissue factor

Question 18

What factors oppose clotting?

Answer 18

Antithrombin III, protein C and protein S

Question 19

What is the enzyme responsible for fibrinolysis?

Answer 19

Plasmin

Question 20

What is the inactive precursor of plasmin?

Answer 20

Plasminogen

Question 21

What is plasminogen activated by?

Answer 21

Tissue plasminogen activator

Question 22

What is streptokinase?

Answer 22

Plasminogen activator - obtained from streptococci

Question 23

What is urokinase?

Answer 23

A plasminogen activator found in urine

Question 24

What is haemophilia A a deficiency in?

Answer 24

Factor VIII

Question 25

How is haemophilia A inherited?

Answer 25

X-linked recessive

Question 26

What would be the results of a blood test of a patient with haemophilia?

Answer 26

Normal platelet count
Normal bleeding time
Normal prothrombin time
Prolonged APTT (measures the intrinsic pathway of which factor VIII is a part)
Low factor VIII assay

Question 27

What is haemophilia B?

Answer 27

Factor IX deficiency

Question 28

What is Von Willebrand Disease caused by?

Answer 28

Deficiency or abnormality in von willebrand factor

Question 29

What are the functions of von Willebrand factor?

Answer 29

Assists in platelet plug formation by attracting circulating platelets to sites of vessel damage and stabilises factor VIII, protecting it from premature destruction

Question 30

How could a patient with von Willebrand disease be diagnosed?

Answer 30

Raised bleeding time and APTT

Common pattern of bleeding is mucosal bleeding reflecting the inadequate platelet function and adhesion

Question 31

How could a patient with thrombocytopenia be diagnosed?

Answer 31

Prolonged bleeding time

Normal PT and APTT (as these assess clotting cascade, not platelet function)

Question 32

What are the causes of thrombocytopenia?

Answer 32

1) Decreased platelet production (eg bone marrow malignancy, drugs, infections, B12 and folate deficiency)
2) Decreased platelet survival (immunologic destruction)
3) Sequestration - in an englarged spleen
4) Dilutional - due to massive blood transfusions (blood stored for more that 24 hours do not contain platelets)

Question 33

What is disseminated intravascular coagulation?

Answer 33

Thrombohaemorrhagic disorder occurring as a secondary complication in a variety of conditions

Question 34

What are thrombophilias?

Answer 34

Inherited or acquired defects of haemostasis resulting in a predisposition to thrombosis

eg factor V leiden, antithrombin deficiency, protein C or protein S deficiency

Question 35

What is bleeding time?

Answer 35

Bleeding time is a medical test done on someone to assess their platelets function

Question 36

What are some diseases that prolong bleeding time?

Answer 36

Thrombocytopenia, von willebrands disease, disseminated intravascular coagulation

Question 37

What is prothrombin time?

Answer 37

Prothrombin time (PT) is a blood test that measures how long it takes blood to clot.