Section 7 - Hemostasis Regulation Flashcards
Protein C
- activation
- functions
- vitamin K dependent
- activated by thrombin-thrombomodulin complex
- inactivates FV and FVIII
- releases tPA
- protein S cofactor necessary for function
Protein S
- forms
- function
- vitamin K dependent
- 60% bound to C4b, 40% free/active
- cofactor for protein C
-> inactivates VIIIa and Va
Protein Z
- forms
- function
- bound to
- vitamin K dependent
- cofactor for ZPI
- degrades factor Xa
-> requires Ca and phospholipids
-> slow on its own, faster as cofactor
Z related protease inhibitor
- function
- bound to
- vitamin K dependent
- cofactor for vitamin Z -> bound = more efficient
- degrades factor Xa (minor degradation of XIa w/o PZ)
Antithrombin
- function
- drug associations
- irreversible complex with thrombin and Xa
- also irreversibly binds: 9-12 and plasmin
- heparin causes conformational change increasing inhibitory effect
Where is heparin formed in the body
Mast cells and tissue basophils
Where is Heparan (heparin like substance) formed in the body
Endothelial cells
Heparin Cofactor II (HCII)
- production
- function
- formed in liver
- specific for thrombin neutralization
- accelerated function with heparin (less than AT+ heparin)
- regulates thrombin on PLT surface
Tissue factor pathway inhibitor (TFPI)
- function
- secretion
- inhibits TFIII release = inhibits extrinsic pathway
- secreted by endothelial cells
Endogenous plasminogen activators
- tPA
- urokinase
- XIIa and Kallikrein
Functions of plasmin and specificity
- fibrinolysis and fibrinogenolysis
- most activity within the clot = fibrin major substrate for activity
- slightly inactivates Va and VIIa
- degrades XIIIa into inactive fragments
define FDP and what it relates to
- primary fibrinolysis and secondary fibrinolysis
- fragments of fibrinogen/fibrin breakdown acting as coagulation inhibitors by attaching to fibrin monomer
- labeled: X, Y, D, E where D and E are end products
describe the difference between fragments E and D in primary fibrinolysis
- fragment D is lysed with A and B fibrinopeptides on the end
- fragment E is the internal fibrinogen portion once fragment D is removed
describe the sequence of events in secondary fibrinolysis
- same as primary except fragment D and E are missing fibrinopeptide A/B via thrombin action
describe the formation of D-dimers
- stabilized fibrin polymers linked at the D domain
- when split by plasmin D domains remain bound together forming the D-Dimer
true or false
D Dimers are present ONLY in Fibrinolysis NOT fibrinogenolysis
true
list the activation factors of plasminogen to plasmin
- FXIIa and Kallikrein
- activated protein C releasing tissue plasminogen factor
alpha 2 - antiplasmin
- function
- role in coagulation
- regulation of fibrinolysis and fibrinogenolysis
- binds and inactivates free circulating plasmin -> rapid inhibitor
- prevents lysis of fibrinogen and degredation of FV and FVIII
alpha 2 - macroglobulin
- function
- role in coagulation
- regulation of fibrinolysis and fibrinogenolysis
- plasmin inhibitor when alpha 2 - antiplasmin is saturated (slower action)
plasminogen activator inhibitors (PAI-1 and PAI-2)
- function
- role in coagulation
- released from
- regulation of fibrinolysis and fibrinogenolysis
- PAI-1 more important than 2
- released from EC and activated platelets
- neutralizes tPA and urokinase
thrombin activatable fibrinolytic inhibitor
- function
- activated by
- feedback loop
- alters fibrin clot = less recognizable for plasmin
- activated by thrombin/thrombomodulin complex
- factor XIa enhances TAFI production
list procoagulants
- platelets
- factors
- fibrinogen
- vWF
list anticoagulants (inhibitors) in normal coag cascade
- not medications
- antithrombin (AT)
- protein C
- protein S
- HCII
- protein Z/ZPI
- TFPI
list profibrinolytics (plasmin activity)
- plasminogen
- tPA
- FXIIa + kallikrein
- urokinase
list antifibrinolytics (regulators)
- PAI-1
- alpha2-antiplasmin
- alpha2-macroglobulin
- TAFI
- FXIa
