Factor 1 aka ?
Fibrinogen
Factor II aka ?
prothrombin
Factor III aka ?
Tissue Factor
Factor V aka?
Proaccelerin, labile factor
Factor VII aka ?
Proconvertin
Factor VIII aka ?
Anti-hemophilic factor
Factor IX aka ?
christmas factor
Factor X aka?
Stuart prower factor
Factor XI aka?
Plasma thromboplastin antecedent
Factor XII aka?
Hageman factor
Factor XIII
Fibrin stabilizing factor
Serine proteases (list)
factor XII, prekallikrein, factor XI, factor IX, factor X, Factor VII, Factor II
(2, 7, 9, 10, 11, 12, PK)
Vit K dependent proteases
Factor II, VII, IX, X, protein C, “Protein S”
2, 7, 9, 10, C, S
Extrinsic tenase made of
TF + VIIa
Intrinsic tenase made of
IXa + VIIIa
Prothrombinase complex
Xa + Va
Contact factors include:
HMWK, PK, FXII
Describe intrinsic coagulation pathway up to Xa
XII, PK, HWMK –> XIIa –> XIa –> IXa (+VIII) –> Xa
12, 11, 9, 8, 10, 5, 2
Describe the common coagulation pathway
Xa (+Va) –> IIa/thrombin –>Fibrin and XIIIa
Describe extrinsic coagulation pathway
TF + VIIa –> Xa (+Va) –> THrombin –> Fibrin and XIIIa
Enzyme complex include _____ + ______ + Ca + Phospholipid surface
protease, cofactor
Vit K causes a post translational modification to _____?
gamma carboxy glutamic acid residue
Warfarin acts by
blocking vit K reductase enzyme (depletes vit K)
vWF two main function is:
- platelet adhesion (vWF to subendothelium)
2. Carrier for factor VIII (t1/2 2-12 hr)
5 main coagulation roles of thrombin
- activate platelets
- Cleaves fibrinogen
- Activates V and VIII (amplification)
- XIIIa - stablize fibrin
- XIa (intrinsic pathway amp)
Thrombin roles for fibrinolysis
- Activates protein C
2. Activates TAFI
Antithrombin III can inhibit _____ and ______
Xa and Thrombin
Unfractionated heparin (cofactor for ________) increase efficiency binding to ___________ and _________
Antithrombin
Xa and Thrombin
LMWH (co factor for ______) increase efficiency binding to _______?
only Xa
Fondaparinux is =?
a pentasaccharide (for heparin) - only helps bind with Xa
C1 (esterase) inhibitor regulates ______ and ______
- Classic complement pathway (immunology)
2. (Vascular) Contact factor (XIa, XIIa, Kallikrein)
Protein C effect is to _______; protein C is classified as _____
Decrease (Va and VIIIa) thrombin - anticoagulant
Protein C zymogen is activated by _____
thrombin
Protein C binds to ________ (cofactor)
Thrombomodulin
______ inhibits protein C binding to thrombomodulin
proinflammatory agents
Factor V leiden definition?
Glu–> Arg mutation - resistant to protein C “APC Resistant”
Factor V leiden effect?
Venous thromboembolism
Warfarin can initially cause _______________? Why?
Transient Hypercoagulable state
Protein C is vit K dependent/short half life
Protein C deficient = cannot lower thrombin –> more clot
Protein C Deficiency would lead to?
thrombosis
TFPI = aka?
Tissue Factor Pathway Inhibitor (TFPI)
TFPI mechanism:
inhibits extrinisic coagulation pathway
Binds Xa –> binds TF-VIIa => Quad complex (TF/TFPI/Xa/VIIa)
TFPI function/results:
prevents atherosclerosis
Plasminogen –> _______
plasmin
Plasmin is a ________ ___________, that breaks down _____, ______, _____
serine protease
Fibrin
Fibrinogen
ECM proteins
tPA = aka?
tissue plasminogen activator
tPA can activate _____ in the prescence of ______
plasminogen, fibrin
tPA is cleaved by ____
Plasmin
uPA = aka?
urokinase plasminogen activator
uPA is synthesized by ?
kidney + endothelial cells (and tumor cells)
uPA was released as:
prourokinase/scu-PA
uPA works by binding to ____, cleaved by ____ which then can cleave ____
fibrin clot, plasmin, plasmin
Deficiency in uPA or tPA
Thrombosis
TAFI activated by?
THrombin-thrombomodulin complex –> exopeptidase
TAFI = Aka?
thrombin activatable fibrinolysis inhibitor
TAFI acts on?
C terminal of proteins (Fibrin) = less plasminogen binding site on fibrin
TAFI regualtes ?
down regulate: PLasmin and clot lysis
PAI-1 = aka?
plasminogen activator inhibitor 1
PAI-1 is stored mostly in
alpha granules in platelets
PAI-1 inhibits ____ and ____
tPA and uPA
PAI1: Deficiency or excess effect
Excessive bleeding Thrombotic events (excess)
a2 - antiplasmin
Binds plasmin 1:1 and inactivates
F13 - links a2-antiplasmin to fibrin
a2-antiplasmin deficiency
bleeding disorder
Endothelial cells express what anticoagulant?
- heparan sulfate & Dermatan sulfate
- Thrombomodulin
- TFPI
Endothelial cells express what fibrinolytic factors
tPA
uPA
Endothelial cells express what anti-plt factors
- PGI2 & NO
2. AMP/Adenosin (from ADP) enzymes
Primary hemostasis concerns with
platelet activation, aggregation, adhesion
Secondary hemostasis concerns with
fibrin clot
protein S is _____ dependent
vit K
Protein S distribution
60% boudn to C4bBP (regulate complement - inactive), 40% free
Protein S is a cofactor to _____?
Protein C/APC