Biochem Coagulation Flashcards
Coagulation factors
Source: plasma and platelets
I (fibrinogen)
IV (Ca)
XIII
vWF
Coagulation factors
Source: plasma only
II (Prothrombin)
VII-XII
Prekallikrein
HMWK
Coagulation factors
Source: sub endothelial tissues
III (tissue factor)
Coagulation factors
Vitamin K
II (Prothrombin)
VII
IX
x
How do endothelial cells inhibit blood clotting?
Heparan sulfate proteoglycans
Prostacyclin (PGI2)
Thrombomodulin
tPA
What are the most abundant receptors on the platelet surface?
GPIIb/IIIa
Coagulation is initiated by the extrinsic pathway when ___. Then what happens?
Tissue factor is exposed to plasma
- tissue factor binds to FVII only in the presence of Ca
- FVII is further activated by FXa or thrombin
- the tissue factor-FVIIa-Ca complex activates FX to FXa and FIX to FIXa
___ has a long half life in circulation, but it is not active unless bound to tissue factor
FVIIa
Formation of ___ is the first step in the final common pathway
FX –> FXa
* activated by the X-ase complex (which includes tissue factor, FVIIa, and Ca)
FXa forms a platelet membrane-bound complex with___. This activates what?
FV
Prothrombin –> thrombin
___ converts fibrinogen to fibrin monomers.
What else does it do?
Thrombin
- activates FVIII, FXI of the intrinsic pathway
- activates FV and FXIII of the common final pathway
- activates FVII of the extrinsic pathway
Intrinsic pathway:
- FXII binds to anionic surfaces
- Prekallikrein and FXI interact with HMWK and are brought close to FXII
- FXII activates prekallikrein to kallikrein which then activates FXII to FXIIa
- FXIIa activates FXI to FXIa
- FXIa activates FIX to FIXa
- FIXa and FVIIIa activate FX to FXa.
- FVIII circulates bound to vWF, which protects FVIII from destruction
Factors involved in anti coagulation:
Source: plasma
Antithrombin (III) Protein C Protein S TFPI Other Serpins
Factors involved in anti coagulation:
Source: endothelial cells
Thrombomodulin
NO
Factors involved in anti coagulation:
Vitamin K
Protein C
Protein S
Where is antithrombin synthesized?
What does it inactivate?
Liver
Thrombin, FIXa, FXa, FXIa, FXIIa
The activity of antithrombin is enhanced by what?
Glucosaminoglycans such as heparin and heparan sulfate
TFPI does what?
Inactivates tissue factor-FVIIa-Ca complex
Proteins and factors involved in fibrinolysis:
Source?
Synthesis of each?
All found in plasma
- Plasminogen-liver
- tPA (Tissue plasminogen activator)-endothelial cells
- uPA (Urokinase, urinary plasminogen activator)-kidney
- Streptokinase- beta hemolytic strep
- PAI-1 (plasminogen activator inhibitor 1)- endothelial cells, liver
- a2-antiplasmin- liver
all of the vitamin K dependent factors require ___
Ca binding
*so all contain gamma-carboxyglutamyl residues
Hemophilia is due to ___
Deficiency in:
FVIII (hemophilia a)
or FIX (hemophilia b)
Bernard soulier disease is due to __
Symptoms are similar to __
Deficiency in GPIb/IX/V
*von Willebrand disease