PBL 9: Anna Casey -Haemostasis

Question 1

What is Virchow’s Triad?

Answer 1

A traid that describes the three factors that contribute to increased thrombosis and how they relate to one another

Question 2

What are the three points of Virchow’s Triad?

Answer 2

1. Blood Vessel Wall
2. Blood Flow (Stasis/Turbulent)
3. Blood Clotting

Question 3

What is Fibrinolysis?

Answer 3

The enzymatic breakdown of the fibrin in blood clots

Question 4

What are the intrinsic and exxtrinsic activators of Plasminogen in Fibrinolysis?

Answer 4

Extrinsic

Tissue Plasminogen Activator
Urokinase
Streptokinase

Intrinsic

Factor XIIa
Kallikrein

Question 5

Outline the process of Fibrinolysis

Answer 5

Plasminogen (activated) → Plasmin → Fibrin (degradation) → Fibrin Degradation Products + Other Anticoagulant effects

Other effects
Precents further activation of fibrinogen

Prevents Polymerisation of existing fibrin

Question 6

Draw the Coagulation Cascade

Answer 6

Question 7

What are the Vitamin K dependent coagulation factors?

Answer 7

II, VII, IX, X, Protein C and S

Question 8

What are the inhibitors of Plasminogen activation in fibrinolysis?

Answer 8

1. Plasminogen Activator Inhibitor
2. Thrombin Activatable Fibrinolysis Inhibitor

Question 9

What are environment risk factors for venous thrombosis?

Answer 9

1. Age
2. Immobility
3. Obesity
4. Oral Contraceptive Pill
5. Trauma/Surgery
6. Thrombphiliia
7. Pregnancy
8. Malignancy
9. Smoking
10. Liver Damage

Question 10

What are environment risk factors for arterial thrombosis?

Answer 10

1. Age
2. Smoking
3. Male
4. Hypertension
5. Strong Family History
6. Hyperlipidaemia
7. Diabetes Mellitus
8. Raised Fibrinogen
9. Liver Damage

Question 11

What is the first step of platelet aggregation in formation of the platelet plug?

Answer 11

1. Platelets bind to collagen through proteins GP1a (directly) and GP1b (through vWF)

Question 12

What is the second step of platelet aggregation in the formation of the platelet plug?

Answer 12

1. Exxposure of GP11b/HP111a which promotes platelet-platelet binding through fibrinogen and vWF.
2. Platelets undergo shape change, exxocytosing their granule contents and releasing pseudopods to increase surface area: TXA2 and ADP promote further aggrefation.

Question 13

What is the role of TXA2 and ADP released from platelet granules?

Answer 13

1. Positive feedback to further promote platelet aggregation and the formation of the plug to prevent temporary blood loss

Question 14

What is the role of the clotting cascade?

Answer 14

T ocrease an insoluble fibrin meshwork to secure the platelet plug nad further decrease blood loss

Question 15

What are the effects of Oestrogen on thrombosis?

Answer 15

• Increases venous dilation
• Downregulates Protein C and S, Antithrombin III, tPA
  Upregulates: Factor II, IX, X

Question 16

What effect does the genetic condition Factor V Leiden on coagulation?

Answer 16

• Point mutation in genes that code for clotting factor V
• Decreases effectiveness of Protein C in inactivating factor Va
• Increases clotting

Question 17

What effect does the genetic condition Prothrombin G20210A have?

Answer 17

Causes elevated plasma prothrombin levels

Increases risk of thrombosis

Question 18

What effect does the genetic condition Protein C and S deficiency have on thrombosis?

Answer 18

1. Decreased proteins lead to increase procoagulation

Question 19

What effect does antithrombin deficiency have on thrombosis risk?

Answer 19

Very high risk of clotting due to decreased antithrombin activity

Question 20

Describe/draw the venous anatomy of the leg

Answer 20

Question 21

What are the hydrodynamic forces and how do they relate to the intra and extra vascular spaces?

Answer 21

1. Intravascular space is the space within blood vessels
2. Extravascular space is the space around blood vessels
3. Hydrodynamic forces are those involved in movement of fluids and proteins from the blood to the tissues

Question 22

How are materials exchanged across the capillaries?

Answer 22

Diffusion

Question 23

Draw a diagram of the hydrodynamic forces influencing fluid movement between intra and extra vascular spaces

Answer 23

Question 24

What are the signs and symptoms of venous thrombosis?

Answer 24

Swelling

Colour Change

Pain

Question 25

What is the differential diagnosis of a painful, swollen leg?

Answer 25

* Snake/Insect Bite * DVT * Baker's Cyst * Allergic Reaction * Infection * Truma

Question 26

What test can we use to diagnose DVT?

Answer 26

* Venography: contrast medium used to image veins -painful and very invasive * Doppler Ultrasound: ultrasound of affected area -can detect flow irregularities * D-Dimer blood test - tests for FDP in blood (fibrin degradation products)

Question 27

Give a brief overview of Injectible anti-coagulant (Heparins)

Answer 27

1. Inhibit coagulation by activation of antithrombin III 2. Antithrombin III inhibitrs thrombin IIa and other serine proteases by binding to the active serine 3. Binds ATIII and increases rate of action 4. Inhibits Xa 5. LMWHs increase action of ATIII on Xa and have longer half-life

Question 28

Give and overview of oral anti-coagulants (Vitamin K antagonists e.g. Warfarin)

Answer 28

1. Warfarin requires frequest blood test to individualize a dose -inconvenient 2. Act only in vivo, interfere with post-translational y-carboxylation of glutamin acid residues in clotting factors II, VII, IXX and X. 3. Inhibit enzymic reduction of vitamin K to its active hydroquinone form 4. Competitive inhibition 5. Onset dependent on t1/2 of factors.

Question 29

What are some common drug interactions of Warfarin?

Answer 29

1. Vitamin K production inhibitors such as antibiotics increase the anticoagulation action of warfarin 2. Increased risk of bleeding especially from the stomach with drugs that cause bleeding by dfifferent mechanisms e.g. aspirin.

Question 30

Give an overview of the mechanisms of Aspirin

Answer 30

1. Taken orally 2. Irreversible antagonist of COX1/2 which causes a decreased TXA2 and therefore causes decreased platelet aggregation 3. Short Half life 4. 7-10 days required for platelet turnover 5. Known to cause GI bleeding: decrease prostaglandins, decreased cell turnover, decreased HCO3-

Question 31

Outline blood replacement therapies

Answer 31

1. Fresh Frozen Plasma: coagulation factors, used for warfarin reveral 2. Packed Red Cell: used for decreased Hb 3. Platelets: treatment of thrombocytopenia, require constant agitation 4. Cryoprecipitate: contrains I, VIII, XIII and vWF, used for tratment of vWF deficiency or factor VIII deficiency Blood must be type matched or haemolysis!