Exam 1 Flashcards
What is the goal of primary hemostasis?
Formation of a platelet plug
How is primary hemostasis accomplished?
vasoconstriction of blood vessels -> platelet adhesion -> platelet secretion of granular content -> platelet aggregation -> formation of platelet plug
What is the goal of secondary hemostasis?
Fibrin clot formation
How is secondary hemostasis accomplished?
activation of coagulation cascade
What is the goal of fibrinolysis?
removal of fibrin clot
How is fibrinolysis accomplished?
Production of plasmin to degrade fibrin
What do endothelial cells in the vascular intima produce that maintain normal blood flor?
prostacyclin - PLT inhibitor and vasodilator
Nitric oxide - induces vasodilation and inhibits PLTs
Tissue factor pathway inhibitor (TFPI) - controls activation of extrinsic pathway
What do endothelial cells produce that inhibit thrombin? (anticoagulants)
Thrombomodulin and Heparan Sulfate
Procoagulant properties of the vascular intima
- can promote vasoconstriction during injury to vessels and expose collagen which activates PLTs
- endothelial cells secrete VWF when activated by thrombin
- secrete P-selectin (promotes PLT and LK binding)
- supports tissue factor
Adhesion of platelets
platelets stick to non-platelet surfaces
Aggregation of platelets
Platelets adhere to eachother
Secretion of platelets
platelets discharge the contents of their granules
Procoagulant: Factor I (nickname and function)
Factor I AKA Fibrinogen
Thrombin substrate, polymerizes to form fibrin
Procoagulant: Factor II (nickname and function)
Factor II AKA Prothrombin
Serine Protease
Procoagulant: Factor III (nickname and function)
Factor III AKA Tissue Factor
Cofactor
Procoagulant: Factor IV (nickname and function)
Factor IV AKA Ionic Calcium
Mineral
Procoagulant: Factor V (nickname and function)
Does not have a nickname
Cofactor
Procoagulant: Factor VII (nickname and function)
Does not have a nickname
Serine Protease
Procoagulant: Factor VIII (nickname and function)
Factor VIII AKA Antihemophilic factor
Cofactor
Procoagulant: VWF (nickname and function)
von Willebrand Factor
Factor VIII carrier and platelet adhesion
Procoagulant: Factor IX (nickname and function)
Factor IX AKA Christmas Factor
Serine protease
Procoagulant: Factor X (nickname and function)
Factor X AKA Stuart-Prower factor
Serine Protease
Procoagulant: Factor XI (nickname and function)
Does not have a nickname
Serine protease
Procoagulant: Factor XII (nickname and function)
Factor XII AKA Hageman factor
Serine protease
Procoagulant: Prekalikrein (nickname and function)
Fletcher Factor, pre-K
Serine protease
Procoagulant: High Molecular Weight Kininogen (nickname and function)
Fitzgerald factor, HMWK
Cofactor
Procoagulant: Factor XIII (nickname and function)
Factor XIII AKA Fibrin-stabilizing factor (FSF)
Transglutaminase
Procoagulant: Platelet Factor 3 (nickname and function)
Phospholipids, phosphatidylserine, PF3
Assembly molecule
What procoagulants are serine proteases?
II, VII, IX, X, XI, XII, Prekallikrein
Which procoagulant has the shortest half-life? What is the half-life?
Factor VII, half-life of 6 hours
Which procoagulant has the highest molecular weight?
VWF
Which procoagulant is found in the highest concentration in the blood?
Factor I (Fibrinogen)
Vitamin-K dependent coagulation factors
Factor II (prothrombin) Factor VII Factor IX (christmas factor) Factor X (stuart-prower factor) Protein C Protein S Protein Z
How does does vitamin K work to activate vitamin-k dependent coagulation factors?
Vitamin K adds a carboxyl group which allows them to bind to calcium. Bound calcium enables vitamin k dependent factors to bind to phospholipids to form complexes with other factors
List the components of the extrinsic tenase complex.
What do these factors activate? (I.e. what is their substrate)
Factor VIIa, Factor III (tissue factor), phospholipid, and calcium
- Activates Factor X (stuart-prower) and factor IX (christmas factor)
List the components of the intrinsic tenase complex. What do these factors activate? (I.e. what is their substrate)
Factor IXa, Factor VIIIa, phospholipid, and calcium
Activates Factor X
List the components of the prothrombinase complex. What do these factors activate? (I.e. what is their substrate)
Factor Xa, Factor Va, phospholipid, and calcium Activates prothrombin (factor II)
What is the purpose of a cofactor?
Binds to its serine protease, allowing the enzyme to be stable and reactive
What is a zymogen?
An inactivated enzyme
Factor II (_________) is transformed into ________, which then acts to transform _________ into ______.
Prothrombin, Thrombin, Fibrinogen, Fibrin
What are the substrates of thrombin?
Fibrinogen, Factor V, Factor VIII, Factor XI, Factor XIII
What is the main enzyme (protease) of the coagulation pathway?
Thrombin
What factor does VWF transport? Why does it need this factor?
Factor VIII; increases half-life
Which coag factors are a part of the intrinsic pathway?
XII, Pre-K, HMWK, XI, IX, VIII, X, V, prothrombin (II), and fibrinogen (I)
Which coag factors are a part of the extrinsic pathway?
VII, X, V, prothrombin (II), and fibrinogen (I)
Which coag factors are a part of the common pathway?
X, V, prothrombin (II), and fibrinogen (I)
What are the contact factors?
Factor XII, HMWK (fitzgerald factor), and pre-K (fletcher factor)
How does thrombin activate fibrin?
Thrombin cleaves fibrinogen, cleaved fibrinogen is a fibrin monomer, exposed fibrin monomer ends come together to form a fibrin polymer
Role of TFPI
serine protease inhibitor (inhibits extrinsic tenase complex)
Function of protein C and protein S
work together to ensure body is not clotting too much; blocks thrombin generation (serine proteases)
role of antithrombin (AT)
serine protease inhibitor (serpin)
role of plasmin
principal enzyme of the fibrinolytic system (serine protease)
function of TPA and UPA
convert plasminogen to plasmin
function of PAI-1
inhibits plasminogen activation by inactivating TPA and UPA
function of alpha-2 antiplasmin
inhibits free plasmin
function of TAFI
inhibits fibrinolysis
Where do D-dimers come from and what does their presence indicate?
they are a product of digestion of fibrin after plasmin breaks them down, their presence may indicate DIC
Neonatal period
First 4 weeks of life
Infancy
First year of life
Childhood
Ages 1 to puberty (8-12 yrs)
Small for gestational age
2500 g or less
Very low birth weight infants
1500g or less
Extremely low birth weight microopremies
1000g or less
Large for gestational age
4000g
How do PT/PTT results in pediatric patients compare to adults?
Pediatrics have a prolonged PT/PTT compared to adults.
How do the coagulation factor levels and regulatory protein levels in pediatrics compare to those in adults?
Pediatrics have decreased coagulation factors and decreased regulatory proteins, which balance eachother out and mean that pediatrics are not more likely to clot and/or have bleeding disorders.
How do coagulation factors/reg proteins in the elderly population compare to regular adults? How does this affect PT/INR?
Elderly have increased coagulation factors the older they get, so elderly patients have increased risk of thrombosis. PT/INR would be decreased, meaning more likely to clot.
How do coagulation factors in pregnant women compare to those of non-pregnant adults?
Pregnant women have increased procoagulants and decreased anticoagulants.
Virchow’s triad - what is it? what are the 3 components?
Determines risk of thrombosis in pregnant women
- Stasis
- Hyper coagulability
- Endothelial damage
reticulated/stress platelets
immature platelets that appear to compensate for thrombocytopenia (too little platelets) - larger than mature PLTs
Platelet plasma membrane
phospholipid bilayer composed of cholesterol and phospholipids
PLT glycocalyx
PLT membrane surface, covers the bilayer
SCCS (surface connected canalicular system)
enables platelets to store hemostatic proteins
route for endocytosis and for secretion of alpha granule content during PLT activation
DTS (dense tubular system)
sequesters calcium and contains enzymes that support PLT activation
alpha granules
alpha granules fuse with SCCS during PLT activation and supports plasma coagulation (50-80 in each PLT)
dense granules
when PLT is activated, dense granules release contents directly into plasma (2-7 in each PLT)
GP Ia/IIa ligand
Collagen
GP VI ligand
Collagen
GP Ib/IX/V ligand
VWF and thrombin
GP IIb/IIIa ligand
Fibrinogen, VWF
TP alpha and TP beta ligand
thromboxane
alpha 2 adrenergic ligand
Epinephrine
PAR1 and PAR4 ligand
Thrombin
P2Y1 and P2Y12 ligand
ADP
white clot
comprised of platelets and VWF -> platelet plug
too many can indicate inappropriate platelet activation
red clot
formed after coagulation occurs -> stabilized fibrin clot
too many can represent inappropriate coagulation
purpose of eicosanoid synthesis pathway
reduces cAMP concentration, increases calcium levels, and activate platelets
main enzyme of the fibrinolytic system
plasmin
what is plasmin’s main substrate?
fibrin