14. Haemostasis 2

Question 1

Normal haemostasis

Answer 1

Balance between fibrinolytic factors and anticoagulant proteins + coagulation factors and platelets

Question 2

What causes bleeding disorders?

Answer 2

Too little pro-coagulant factors (VIII,IX,XI)

Too many anticoagulant factors

Question 3

List 4 characteristics of abnormal bleeding

Answer 3

‘Spontaneous’
Out of proportion to the trauma/injury
Unduly prolonged
Restarts after appearing to stop

Question 4

What clinical feature is common to all bleeding disorders?

Answer 4

Easy bruising

Question 5

Give 3 examples of significant bleeds

Answer 5

Nosebleed not stopped by 10 mins compression
Cutaneous haemorrhage
Prolonged (>15 mins) bleeding from trivial wounds

Question 6

List 3 defects of primary haemostasis

Answer 6

Deficiency or defective:
Collagen (steroid therapy, age, scurvy)
Von Willebrand factor (genetic disease)
Platelets (aspirin, thrombocytopenia)

Question 7

What happens to patients with Von Willebrand factor deficiency?

Answer 7

Damaged vessel wall
But no VWF, so platelets can’t stick (as move too fast)
Patient bleeds as can’t form primary haemostatic plug
(bleed from outset)

Question 8

Describe the pattern of bleeding of a defect in primary haemostasis.

Answer 8

Immediate
Easy bruising
Nosebleeds (prolonged: >20 mins)
Gum bleeding (prolonged)
Menorrhagia (anaemia)

Question 9

What is a characteristic feature of thrombocytopenia?

Answer 9

Petechiae (bleeding spots)

Question 10

What is the main role of primary haemostasis?

Answer 10

Formation of an unstable platelet plug
(through platelet adhesion and aggregation)
Limits blood loss and provides surface for coagulation

Question 11

What is the main role of secondary haemostasis?

Answer 11

Stabilisation of the platelet plug with fibrin
Blood coagulation
Stops blood loss

Question 12

Why is there a lag between the administration of a tissue factor trigger and the thrombin burst?

Answer 12

This is when cofactors and clotting factors are synthesised.

Question 13

Describe the cause of haemophilia A

Answer 13

There is insufficient FVIII
Thrombin generation “boost” doesn’t happen
Failure of thrombin generation
Failure to generate fibrin mesh to stabilise platelet plug

Question 14

Attempted haemostasis in haemophilia A

Answer 14

Primary haemostatic plug forms so initially stop bleeding, but it doesn’t get stabilised so falls apart

Question 15

Defects of secondary haemostasis

Answer 15

Deficiency or defect of coagulation factors

Poor thrombin burst, poor fibrin mesh

Question 16

Genetic defects of secondary haemostasis

Answer 16

Haemophilia: FVIII or FIX deficiency

Question 17

List 4 acquired disorders of secondary haemostasis

Answer 17

Liver disease (most coagulation factors are made in the liver)
Drugs (warfarin: inhibits synthesis, others block function)
Dilution (results from volume replacement: when not enough plasma is replaced)
Consumption (DIC)

Question 18

What is DIC an abbreviation for? What is DIC?

Answer 18

Disseminated intravascular coagulation
Generalised activation of the coagulation- expression of tissue factor inside vasculature
Consumes and depletes clotting factors and platelets
Activates fibrinolysis- depletes fibrinogen

Question 19

What is DIC associated with?

Answer 19

Sepsis
Major tissue damage
Inflammation

Question 20

What are the consequences of DIC?

Answer 20

Widespread bleeding

Deposition of fibrin in vessels causes organ failure

Question 21

Describe the pattern of bleeding of defects in secondary haemostasis.

Answer 21

Delayed (after primary haemostasis)
Prolonged
Bleed deeper into joints and muscles. 
Not from small cuts (primary haemostasis is fine)
Nosebleeds rare
Bleeding after trauma/ surgery 
Easy bruising

Question 22

What is the hallmark of haemophilia?

Answer 22

Haemarthrosis: bleeding into joints

Question 23

Defects in fibrinolysis prevalence

Answer 23

Not so common

Question 24

What will excess fibrinolytic activity cause?

Answer 24

Excess bleeding

Question 25

State 2 defects of clot stability

Answer 25

``` Excess fibrinolytic (plasmin, tPA) Deficient antifibrinolytic (antiplasmin) ```

Question 26

What causes excess fibrinolytic activity (plasmin, TPA)?

Answer 26

``` Therapeutic administration (given to people with strokes to break down blood clot) Some tumours ```

Question 27

What causes deficient antifibrinolytic activity (antiplasmin))?

Answer 27

Antiplasmin deficiency (genetic)

Question 28

What causes anticoagulant excess?

Answer 28

Usually therapeutic administration e.g. Heparin (which activates antithrombin)

Question 29

Describe the characteristics of thrombosis

Answer 29

``` Excess FVIII Increased procoagulant activity Deficient anticoagulant activity Blood clot should not have been formed, unnecessary, not preceded by bleeding Blood vessel intact with clot inside it Pathological clot formation ```

Question 30

What are the effects of thrombosis?

Answer 30

Obstructed flow of blood | Embolism (migration of the thrombus)

Question 31

What may obstructed flow in an artery or vein cause?

Answer 31

Artery: stops blood flow to organ/ area of tissue, usually more immediately serious e.g. MI, stroke, limb ischaemia Vein: blood can usually still return to heart via a different route. May cause pain/ swelling

Question 32

What may arterial emboli cause?

Answer 32

Stroke | Limb ischaemia

Question 33

What may venous emboli cause?

Answer 33

``` Pulmonary embolism (shortness of breath, chest pain, sudden death) ```

Question 34

Deep vein thrombosis

Answer 34

Venous return of blood obstructed | painful, swollen leg

Question 35

How does risk of thrombosis change with age?

Answer 35

Increases

Question 36

What are the 4 consequences of thromboembolism?

Answer 36

Death Recurrence Thrombophlebitic syndrome Pulmonary hypertension

Question 37

List 3 possible contributory factors to thrombosis

Answer 37

Genetics Acute stimulus Effect of age, illness, medication

Question 38

What are the 3 components of Virchow's triad?

Answer 38

``` Blood hypercoagulability (dominant in venous thrombosis) Vessel wall injury (dominant in arterial thrombosis) Stasis (contributes to both) ```

Question 39

Increased risk of Venous thrombosis: Blood

Answer 39

Deficiency of anticoagulant proteins e.g. Antithrombin | Increased coagulant proteins e.g. FVIII

Question 40

Increased risk of Arterial thrombosis: vessel wall

Answer 40

Many proteins active in coagulation are expressed on the surface of endothelial cells e.g. Thrombomodulin Expression is altered in inflammation e.g. infection

Question 41

Increased risk of thrombosis: Flow

Answer 41

Reduced flow (stasis) increases the risk of venous thrombosis e.g.: surgery, fracture

Question 42

What do people with Thrombophilia have an increased tendency of?

Answer 42

Increased tendency of thrombosis

Question 43

What are the signs of thrombophilia?

Answer 43

Thrombosis at young age Idiopathic thrombosis Multiple thromboses Thrombosis whist anticoagulated

Question 44

Which 4 conditions will alter blood coagulation, vessel wall and/ or flow to precipitate thrombosis?

Answer 44

Pregnancy Malignancy Surgery Inflammatory response

Question 45

What is lysing thrombi not often a method of treatment?

Answer 45

There is a high risk of bleeding

Question 46

What is the main approach to treating thrombi?

Answer 46

Limit recurrence/ extension/ emboli: Increase anticoagulant activity e.g. heparin Decrease procoagulant factors e.g. Warfarin Inhibit procoagulant factors