Summary: Hemostasis - Bleeding Disorders

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• 1 Vessel wall and platelets

• Which parts of the vessel wall initiates clot formation?

  • Collagen: activation of platelets 
    
  • Tissue factor: activation of extrinsic route (coagulation) 
  • VWF: binds platelets to collagen 
  • Platelet activation factor 

• What are the function of the platelets?

  • Adhesion 
  • Aggregation 
  • Activation 
  • Secretion 
  • alfa granules: VWF, fibrinogen 
  • dense granules: ADP, serotonin 
  • Initiation of coagulation by P2Y12
  • Production of TXA2

• What are the most important platelet membrane receptors and what is the function of them?

  • GPIa/IIa: binds collagen
    
  • GPIb/IX/V: binds VWF in plasma, and VWF binds to collagen
  • GPIIa/IIIa: binds to fibrinogen (aggregation)
  • P2Y12: interaction with coagulation factors

• What are the functions of thromboxane A2 (TXA2) and prostacycline (PGI2)?

  Thromboxane A2 (TXA2) is produced in platelets. Its functions are vasoconstriction, decreasing of cAMP, initiation of platelet release, induction of platelet aggregation and adhesion.
  
  
  Prostacycline (PGI2) is produced in the endothelium. Its functions are vasodilatation, increasing cAMP, prevention of platelet aggregation to a normal vessel wall, limitation of the initial platelet plug.

• How is VWF produced, stored and released?

  Produced by three different ways: 
  

  • Platelet alfa granules 
  • Constitutive pathways by endothelium 
  • regulated pathway by endothelium 

  
  
  VWF is stored in the Weibel-Palade bodies. The multimeres are rich in UL forms. In activation of the endothelium the released UL-VWF are proteolyzed by ADAMTS13 into smaller multimeres. 

• What is the function of ADAMTS13?

  Proteolyses ultra-high-molecular-weight forms of VWF, which are secreted by the endothelial cells to form the multimeres that are normally present in plasma.

• 2 Coagulation cascade

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• Which enzyme has a key role in the coagulation? What are the main functions of this enzyme?

  Thrombin (FIIa)
  
  High concentration of thrombin --> procoagulant
  

  • Fibrin formation
  • stimulation of FXIa to make extra thrombin
  • thrombomodulin activated TAFI to inhibit fibrinolysis 

  
  
  Low concentration of thrombin --> anticoagulant
  

  • Thrombomodulin activated protein C and S to inhibit FVIII and FV

• What are the most important inhibitors of the coagulation cascade?

  • Thrombomodulin activated protein C and S --> inactivated FV and FVIII

  • TAFI inhibited: leads to fibrinolysis
  • Antithrombin: inactivated thrombin, FX, FXII, FXI, FIX and FII
    
    
    

• 3 Clinical disorders - Primary hemostasis

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• What are the most common symptoms of the primary hemostasis?

  • Bruising 
    
  • Nose and gum bleeds 
  • Bleeding occurs directly and won't stop

• What are the confirmation tests for the primary hemostasis?

  • VWF tests
    
  • Platelet size and morphology 
  • light aggregometry for ADP, collagen, ristocetin or arachid