Exam 1 Flashcards
What is the goal of primary hemostasis
the formation of a platelet plug
List out the steps of primary hemostasis
- vascular damage occurs
- vasoconstriction
- platelets activate
- platelets adhere to injury
- platelets secrete granule content
- platelets aggregate
- platelet plug is formed
What is the goal of secondary hemostasis
to form a stable fibrin clot
List out the steps of how secondary hemostasis occurs
- proteins are in blood as inactive zymogens
- a complex forms that activates the zymogens
- coagulation cascade occurs
- thrombin is produced
- thrombin converts fibrinogen into fibrin
What is the final stage of hemostasis?
fibrinolysis- the digestion and removal of fibrin clot
How do endothelial cells that line the inner surface of blood vessels influence in coagulation?
They can secrete anticoagulant and procoagulant molecules that move the coagulation cascade along
What are the anticoagulant properties of intact vascular intima
prevents thrombosis by:
inhibiting platelet aggregation
preventing coag activation and propagation
enhancing fibrinolysis
What procoagulants can endothelial cells secrete
VWF P-selectin exposure of collagen PAI-1 TAF1 ADAMTS13
What anticoagulants can endothelial cells secrete
nitrous oxide PGI2 heparan TFPI Thrombomodulin EPCR TPA
What does prostacyclin do
inhibits platelets and is a vasodilator
What does nitric oxide do?
inhibits platelet activation, promotes angiogenesis
What does TFPI stand for and what does it do?
Tissue factor pathway inhibitor
controls activation of extrinsic pathaway
What does thrombomodulin do?
EPCR binds protein C–> thrombomodulin catalyzes activation of protein C pathway
Ends in thrombin inhibition
What does heparan sulfate do?
enhances activity of antithrombin
What is VWF? What does it do
it is secreted by endothelial cells, activated by thrombin,
the carpet on which platelets assemble
What do ICAMs, PECAMs and P selectin do?
they are adhesion molecules that promote platelet and leukocyte binding
What causes the coagulation system to activate? Extrinsic pathway
the exposure of Tissue factor which is right on the outside of the inner vessel lining.
TF needs to have contact with F VII
What do endothelial cells secrete to promote fibrinolysis?
TPA- tissue plasminogen activator
PAI-1- plasminogen activator inhibitor
TAFI-thrombin activatable fibrinolysis inhibitor
all preventing excessive plasmin generation
What molecule allows platelets to adhere
VWF- links platelets to collagen
What molecule allows platelets to aggregate
GP llb/lla receptors on platelets that are activated and allow fibrinogen, VWF and fibronectin to bind to platelets. Fibrinogen is the key player
What do platelets secrete out of their granules
procoagulants- V, VWF, VIII and fibrinogen
control proteins-Ca, ADP
What is the main ingredient for enzyme-cofactor- substrate complex to form
the platelet membrane must be activated, this is the foundation for secondary hemostasis
Where do coagulation factors come from? How many are there?
the liver, 16
What is a zymogen?
an inactive enzyme
What are cofactors and what is their role
coagulation factors the help bind, stabilize and enhance activity of enzymes
What is the primary enzyme of the coagulation system
thrombin,
What is the substrate for the primary enzyme of the coag system
fibrinogen
What coagulation factor has the shortest half life? What is it?
VII- 6hr half life
What coagulation factor has the highest molecular weight
VWF-its really big
What coagulation factor if most concentrated in the blood?
I- fibrinogen
What coagulation factor if most concentrated in the blood?
I- fibrinogen
What is are the nicknames for coagulation factors I II III IV
I-fibrinogen
II-prothrombin
III-Tissue factor
IV- ionic Ca
What are the nicknames for coagulation factors
V
VII
VIII
V- five
VII- seven
VII- antihemophilic factor
What are the nicknames for coagulation factors IX X XI XII
IX-Christmas factor
X-Stuart Prower factor
XI-eleven
XII-Hageman factor
What are the nicknames for coagulation factors pre-k HMWK XIII PF3
pre-K fletcher factor-prekallikrein
HMWK- Fitzgerald factor-high molecular weight kininogen
XIII-fibrin stabilizing factor
PF3- platelet factor 3
Which coagulation factors are serine proteases
II-prothrombin VII-seven IX-Christmas X-Stuart XI-11 XII-Hageman pre-k- pre kallikrein-fletcher 2+7=9, 10, 11, 12 prek
Which coagulation factor carries factor VIII and allows for platelet adhesion
VWF
What coagulation factors function as cofactors
III-TF V-5 VIII- antihemophilic factor HMWK- kininogen- Fitzgerald 3+5=8 HMWK
Which coagulation factor functions as a mineral
IV- ionic Ca
Which coagulation factor is a thrombin substrate, and polymerizes to create fibrin
fibrinogen
Which coagulation factor functions as transglutaminase and transamidase? enzymes
XIII- fibrin stabilizing factor
Which coagulation factor functions as an assembly molecule?
platelet factor 3
What do serine proteases do?
they are enzymes that act on a substrate by digesting the primary backbone,
state as inactive zymogens
Which coagulation factors are vitamin K dependent?
II, VII, IX, X
2+7=9, 10
Where is vitamin K found in a person’s diet
green leafy vegetables
quinone, also produced by some bacteria
What is the function of vitamin K
catalyzes a change in the prothrombin group proteins
What is the prothrombin group
the group of vitamin K dependent coag factors
What regulatory proteins act on each of the members of the prothrombin group
II-C
VII-S
IX-Z
X- none
How does vitamin K activate the factors in the prothrombin group
adds a carboxyl group
enabling the factor to bind to ionic Ca (IV)
The bound Ca allows vitamin K to add charged phospholipids to the coag factor
coag complexes help continue coagulation cascade
What are the 3 coagulation complexes
Extrinsic
intrinsic
prothromninase
What are the components of the extrinsic tenase complex, what does it activate
TF, Ca, VIIa, phospholipid
IX and X
What are the components of the intrinsic tenase complex, what does it activate?
IXa, VIIIa, phospholipid, Ca
X
What are the components of prothrombinase, what do they activate?
Xa, Va, phospholipid, Ca
prothrombin
What does BK stand for
bradykinin
What lab test detects the absence of any of the factors in the intrinsic pathway
aPTT or PTT
What lab test measures the extrinsic pathway function?
PT
What are the procoagulants involved in the coag cascade
V-
VWF
VIII
Fribrinogen
What are the two phases of coagulation? how much thrombin do each of them produce
initiation- TF expressing cells- 3-5% of total thrombin- extrinsic
propagation- on platelets, produces 95% or more of thrombin-intrinsic
What is the principal enzyme of fibrinolysis
plasmin- hydrolysis off fibrin
How is plasminogen converted to plasmin
TPA Tissue plasminogen activator TPA
UPA- urokinase plasminogen activator - less effective
Where does TPA come from? and UPA?
TPA-secreted by endothelium
UPA-kidney cells
How is plasminogen inhibited?
PAI-1- inhibits TPA and UPA-plasminogen never turns to plasmin
alpha 2- antiplasmin- inhibits free plasmin
TAFI- thrombin activatable fibrinolysis inhibitor- blocks TPA and plasminogen from binding
What do fibrin fragments do
XYDE
inhibit hemostasis, products of fibrin digestion
What are contact factors?
factors that are activated by contact with a negative charge to become activated
What are the contact factors
XIIa, HMWK, prek- activates factor XII
How does thrombin activate fibrinogen
thrombin cleaves fibrinopeptides, and A and B from alpha and beta chains
Which procoagulant is the most concentrated
fibrinogen
What are the pediatric developmental stages
neonatal- first 4 weeks
infancy first year
childhood 1 to puberty
How are infants categorized by weight
large more than 4000
small 2500 or less
very low 1500 or less
extremely low 1000 or less
Who are more at risk of thrombosis
babies- No
elderly - yes
pregnancy -yes very
Difference between white clot and red
White-platelets and VWF
Red- after coag- stabilized clot
What triggers the eicosanoid synthesis pathway
G proteins
What is the purpose of the eicosanoid synthesis process
To activate platelets
The ___ Camp you have the __ platelet activation
less camp
more platelet activation
where does arachadonic acid come from
phospholipids
Why is arachadonic acid important
inflammation and vasodialation
What affects the zone of inhibition and susceptibility breakpoints
the thickness of agar
too thick-falsely small zones (false resistance)
too thin-falsely large zones (false susceptibility)
What is the purpose of placing plates with KB upside down
to avoid condensation interfering with results
What is the maximum of antibiotic disks per mueller hinton plate
12 for every 150 mm plate
What temperature can Kirby Bauer Disks be stored and for how long
2-8C for 1 week
needs to be at room temp before use
What does the MecA gene cause resistance for
codes for penicillinases- penicillin binding protein PBP2a
causes resistance to penicillin, methicillin, nafcillin, cloxacillin, dicloxacillin
What are MRSA and what are the resistant to
oxacillin resistant Staph aureus
What special properties do oxacillin disks have
modified mueller hinton plate with oxacillin with McFarland suspension
What resistance does the erm gene cause
encodes for methylation 23S RNA
causes resistance to erythromycin
induces clindamycin
What resistance does the msrA gene cause?
encodes for efflux mechanism that gives resistance to erythromycin
susceptible to clindamycin
What is the D test for
to see if there is resistance to both erythromycin and clindamycin
What does it mean if the clindamycin zone is flattened in a D test
erm gene present
resistance to clindamycin
What does it mean if a D test is not flattened and there is resistance in the erythromycin only
msrA gene present
not resistant to clindamycin
What is the MHT modified Hodge Test for?
looks for carbapenemase enzyme in enterobacteriaceae
gives them ability to neutralize beta lactam carbapenems
if test is positive, resistant to all carbapenems
clover shape
