1.3 Haemostasis and Bleeding Disorders

Question 1

What is haemostasis?

Answer 1

A mechanism to stop bleeding involving multiple integrated steps resulting in the foramtion of a plug that closes the damaged site on the blood vessel.

Question 2

What are the 4 steps of haemostasis?

Answer 2

1. Vascoconstriction
2. Priamry haemostasis
3. Secondary haemostasis
4. Fibrinolysis

Question 3

What is vasoconstriction?

Answer 3

Vascular spasm of smooth muscle in vessel walls, which narrow vessel and slow blood flow

Slow blood flow = contact activation of platelets + coagulation factors

Transient effect, loaclised to damaged area

Mediated by sympathic nervous system and enhanced by local secretin factors (endothelin)

Question 4

What is primary haemostasis?

Answer 4

Platelet adherence to vessel walls by binding VW factor on collagen surface

Question 5

What are platelets?

Answer 5

Small, thin cell filaments broken from megakaryocytes in bone marrow in a process called thombopoiesis

Question 6

What happens when platelets activate?

Answer 6

Shape change (pseudopodia) = arms to grab each other better

Degranulation (promotes further vasoconstriction)

Question 7

What is secondary haemostasis?

Answer 7

Fibrin starts to be deposited

Question 8

The coagulation cascade is part of secondary haemostasis. How does it work?

Question 9

What is the difference between platelet activation and platelet aggregation?

Answer 9

Platelet activation = shape change + secretion of granules

Platelet aggregation = recruit additional platelets to form plug

Question 10

What is the mechanism behind depositing fibrin as part of secondary haemostasis?

Answer 10

1. Tissue factor exposure activates coagulation cascade to generate thrombin
2. Cleaves fibrinogen into insoluble fibrin (meshwork)
3. Activates platelets to form primary plug

Question 11

The coagulation cascade is an important part of the secondary haemostasis mechanism. How does the cascade work?

Answer 11

Activation of a series clotting factors to increase stabilisation

1. Each enzyme is in its inactive form (zymogen)
2. Activation catalyses the next reaction and so on
3. Results in thrombin production (thrombin activates platelets)

Question 12

What are the 3 pathways that make up the coagulation cascade?

Answer 12

1. Extrinsic = repsone to damage (fast + short, vit. K dependant)
2. Intrinsic = exposure to collagen (longer than extrinsic)
3. Common = activation of factor X via extrinsic + intrinsic pathways (thombin + clot stabilisation)

Question 13

What is fibrinolysis?

Answer 13

Clot stabilisation + resorption

Prevents clot from growing + causing problems from plasmin formation (plasmin breaks down clot - fibrinogen + fibrin)

Question 14

Plasmin causes the clot to breakdown by lysing fibrinogen + fibrin. How is plasmin formed?

Answer 14

Tissue plasminogen activators (tPA) is released from endothelial cells during coagulation cascade

Plasmin formation = fibrinolysis

Question 15

What are the 3 kinds of inherited bleeding disorders?

Answer 15

1. Absence / deficiency of clotting factors
2. Haemophilia
3. Von Willebrand disease

Question 16

What are the 2 examples of platelet disorders?

Answer 16

1. Thrombocytopenia (platelet deficiency)
2. Drugs impairing platelet function (alcohol, analgesics, antibiotics, antidiabetics, cytotoxics, anaesthetics)

Question 17

What are the 4 ways thrombocytopenia causes platelet deficiency?

Answer 17

1. Reduced production
2. Increased destruction
3. Impaired function
4. Presence of inhibitors

Question 18

What is haemophilia?

Answer 18

A deficiency in an enzyme in the coagulation cascade

Causes excessive bleeding from cuts/injuries = bad news for internal

Question 19

What are the two types of haemophilia and their associated missing factor?

Answer 19

1. Haemophilia A = missing factor VIII
2. Haemophilia B = missing factor IX

Question 20

What is von Willebrand disease?

Answer 20

Inherited disease causing low levels of VW factor

Mild forms don’t require treatment

Symptoms = easy bruising, nose bleeds, excess bleeding during menstruation, blood in urine/stool

Question 21

What are the characteristics of the 3 types of von Williebrand disease?

Answer 21

Type 1 = most common (80%), VWF work normal but not enough present

Type 2 = VWF normal, but not funcitioning properly

Type 3 = Rare + most severe bleeding, little to no VWF

Question 22

What are the 4 kinds of acquired coagulation disorders?

Answer 22

1. Vitamin K deficiency (most common, esp babies, vit K necessary for coagulation cascade)
2. Liver disease (livers produce almost all coagulation factors)
3. Drug induced
4. Disseminated intravascular coagulation (DIC) = development of small clots in bloodstream