12.2 Blood Coagulation

Question 1

What is haemostasis?

Answer 1

Is a process to prevent & stop bleeding

Purpose:

1. STOP haemorrhage
2. PREVENT haemorrhage
3. MAINTAIN flow

Question 2

What are some disorders to do with haemostasis?

Answer 2

• THROMBOSIS
  
  • ​E**xcess/innapropriate ‘clotting’
  • e.g.
    
    • ARTERIAL
      
      • Coronary thrombosis
      • Thrombotic stroke
    • VENOUS
      
      • ​DVT
      • PE
• HAEMORRHAGE
  
  • ​Excess/innapropriate ‘bleeding’
  • e.g.
    
    • Trauma
    • Haemophilia
    • von Willebrand disease

Question 3

What does the endothelium produce? (substances & what they do?)

Answer 3

• VASOactive mediators
  
  1. ​​Endothelin = vasoCONstrictor
  2. Prostacyclin (PGI2) = vasoDILator
  3. Nitric oxide (NO) = vasoDILator
  4. Injury/damage/disease = vasoCONstriction
• Haemostatic agents
  
  • ​Von Willebrand factor (vWF)

Question 4

Explain what von Willebrand disease is & treatment

Answer 4

• Common bleeding disorder
• Deficient/dysfunctional vWF

​TREATMENT

• Desmopressin (ADH)

Question 5

What are the layers of a blood vessel?

Answer 5

Question 6

What happens following blood vessel injury?

Answer 6

1. VASOSPASM
   
   • Causes LESS blood loss
2. INCREASE in pro-thrombic mediators
   
   • ​​vWF (in blood)
   • Collagen (‘captures’ & activates platelets)
   • Tissue factor (triggers coagulation)

Question 7

List some anticoagulant drugs & their targets

Answer 7

1. Dabigatran
   
   • ​​Thrombin IIa inhibitor
2. Rivaroxaban
   
   • ​​Factor Xa inhibitor
3. Heparin
   
   • ​​ATIII –> IIa + Xa inhibior
4. Warfarin
5. Citrate & EDTA
   
   • Ca2+ inhibitor (binds with Ca2+ preventing Ca2+ doing its function)

Question 8

Name a fibrolytic drug & its target

Answer 8

1. Alteplase
   
   • ​​tPA –> plasminogen inhibitor

Question 9

List some antiplatelet drugs

Answer 9

1. Tirofiban
2. Aspirin
3. Clopidogrel
4. Ticagrelor

Question 10

What is the class, pharmacology, physiology, clinical of rivaroxiban?

Answer 10

• CLASS: NOAC = novel oral anticoagulant
  
  • Direct Factor Xa inhibitor
• PHARMACOLOGY:
  
  • Target: FXa (prothrombinase complex)
  • Activity: competitive inhibitor
• PHYSIOLOGY:
  
  1. Anticoagulant
  2. ↓thrombin generation
• CLINICAL:
  
  • Treatment/prophylaxis DVT* & *PE

Question 11

What is the class, pharmacology, physiology, clinical of alteplase?

Answer 11

• CLASS: Fibrinolytic
• PHARMACOLOGY:
  
  • Target: Plasminogen
  • Activity: activator
• PHYSIOLOGY:
  
  1. Promotes endogenous fibrinolytic system
  2. Thrombus dissolution
• CLINICAL:
  
  • Acute myocardial infarction
  • Pulmonary embolism
  • Ischaemic stroke

Question 12

What is the class, pharmacology, physiology, clinical of dabigatran?

Answer 12

• CLASS: NOAC = novel oral anticoagulant
  
  • Direct thrombin inhibitor
  • Prodrug, non-peptide
• PHARMACOLOGY:
  
  • Target: thrombin FIIa (enzyme)
  • Activity: competitive, reversible inhibitor
• PHYSIOLOGY:
  
  1. Anticoagulant; ↓fibrin formation
  2. ↓thrombin-induced platelet aggregation
• CLINICAL:
  
  • Treatment/prophylaxis DVT & PE

Question 13

Explain heparin

Answer 13

• Heparin is isolated from the LIVER (e.g. from animal sources)
• UNfractioned heparin has a HIGHER MW (molecular weight) range than LMWH
• Contains a pentasaccharide which mediates binding to ATIII
• ATIII/heparin –> inhibits factor IIa & Xa

HEPARIN = INCREASE sulphates & STRONG -ve charge

HEPARAN = LESS sulphates

They both have repeating disaccharides

Question 14

Give examples of LMWH & why it is preferred to UNfractioned heparin?

Answer 14

• LMWH gives BETTER, consistent response with FEWER side effects

1. Dalte_parin_
2. Tinza_parin_**​

Question 15

What does fibrinogen become in blood coagulation & explain both substrate & product?

Answer 15

Question 16

Steps in fibrinogen (multiple)

Answer 16

Question 17

What does prothrombin become in blood coagulation & how? (explain substrate & product)

Answer 17

Question 18

What does Factor X become in blood coagulation & explain substrate & product?

Answer 18

Question 19

What does factor V become in blood coagulation (& explain substrate & product)?

Answer 19

Question 20

Explain factor IX

Answer 20

Question 21

Explain factor VII

Answer 21

Question 22

Explain factor III

Answer 22

Question 23

Explain antithrombin-III

Answer 23

Question 24

What does factor XIII become in blood coagulation (& explain substrate & product)?

Answer 24

Question 25

Explain what **thrombin** (factor IIa) activates & how

Answer 25

Question 26

Draw a diagram of how **intrinsic** & **extrinsic** factors form a *fibrin polymer*

Answer 26

Question 27

Draw a schematic of how a **fibrin polymer** becomes a **fibrin clot**

Answer 27

Question 28

Explain **fondaparinux**

Answer 28

Question 29

What are some *in vitro* **antigoagulants** & why are they used?

Answer 29

* Blood clots EASILY this use them (e.g. *citrate*) to DECREASE *coagulation* e. g. * **Chelators** 1. ↓ free [Ca2+] 2. Disrupts *V, VIII, XIII* and *Vit-K dependent factors* (II, VII, IX, X) * **Citrate** * ​*_Moderate_* anti-coagulant * **EDTA** * **​***_VERY strong_* anti-coagulant

Question 30

What does **plasminogen** become in blood coagulation (& explain substrate & product)?

Answer 30