Biochemistry thrombosis and homeostasis - Secondary hemostasis
4 important questions on Biochemistry thrombosis and homeostasis - Secondary hemostasis
Explain the activation of blood coagulation
Thrombin transforms fibrinogen to fibirn and is mass produced (in short time) to do so.
Initiation
- Tissue factor / Factor 7a complex → activates factor 10 and factor 9
- factor 7a complex
- tissue factor (transmembrane domain
- Gla domain (modified glutamic acids that bind phospholipids)
- y-carboxylation of glutamic acids
- dependent on vitamine K
- Vitamin K antagonist and inhibits vitamin K reductase thereby limiting the activity of the vitamin K dependent carboxylase
Amplification and
- complex formation between factor 8a/factor 9a and factor 5a/factor 10a
To which factor is the X-linked bleeding disorder hemophilia linked?
Hemophilia B: factor 9
- X-linked = only in male
- treated with purified factor 8 or 9, administrated intravenously
- treatment expensive and only available in the developed countries
- FVIII or antiFIX-FX
- Emicizumab vs factor 8
- Gene therapy
Explain the conversion of prothrombin into thrombin and by which factor?
- Feedback activation of factor 10, factor 9 and factor 8 amplifies thrombin formation
- Cleavage by thrombin converts fibrinogen into fibrin by releasing
- Factor 8a cross-links soluble fibrin into insoluble fibrin clots
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How is the disease called, causing risk factor for venous thrombosis?
Which factor is mutated?
- Factor 5 is mutated at cleavage site for APC
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