Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
103 Cards in this Set
- Front
- Back
|
Clotting activators
|
Coagulation factors, phospholipids, and Ca
|
|
|
Fibrinolysis inihibitors
|
PAI-1, PAI-2, PAI-3 , Alpha 2 antitripson, TAF 1.
|
|
|
Principle of fibrinolysis system
|
dissolves the clot by proteolysis, they initiates same time as coagulation. System are interrelated, gradual process from large to small fragments of fibrin.
|
|
|
Fibrinolysis system disolve the clot by
|
proteolysis
|
|
|
Componenets that activators in fibrinolysis system for
|
Activators to convert plasminogen to plasmin
|
|
|
Componenets that inactivate in fibrinolysis system for
|
inactivare plasminogen
|
|
|
Componenets that inhibitors in fibrinolysis system for
|
inhibition of fibrinolysis.
|
|
|
Activaters of fibrinolysis
|
TPA - tissue plasminogen activator, Kallekrein, Urokinase and streptokinase
|
|
|
TPA - tissue plasminogen activator - released from
|
injured tissue - endothelium
|
|
|
When is TPA - tissue plasminogen activator - released
|
same time as tissue thromboplastin.
|
|
|
TPA - tissue plasminogen activator ise used in therapeutically by
|
in vivo to disolve clots.
|
|
|
TPA - tissue plasminogen activator acts on where
|
fibrin bound plasminogen, not on free circulating plasminogen.
|
|
|
fucntion of Kallekrein
|
it is part of contact system that is an activater of fibrinolysis. Convert plasmiongen to plasmin
|
|
|
Fucntion of Urokinase and where is it produced
|
it is part of contact system that is an activater of fibrinolysis. Convert plasmiongen to plasmin. It is prodiced from renal cells in kidney
|
|
|
Streptokinase function and how is t used
|
it is an activater of fibrinolysis. It is used in therapeutically in vivo.
|
|
|
2 activators of fibrinolysis that can use as therapeutically in vivo
|
TPA - tissue plasminogen activator, and streptokinase
|
|
|
substrates that plasmin acts on
|
fibrin, fibrinogen, and coagulation factors.
|
|
|
Coagulation factors that plasmin destroy
|
factor V and VIII so they acts as coagulaton inhibitors.
|
|
|
Plasmin action is limites to clot site by
|
limited to clot site by inhibitors of plasmin
|
|
|
Amount of FDP in normal people
|
present in snall amount.
|
|
|
when is FDP elevated.
|
where there is more cloting. Such as Trama, surgery, imbalences in clotting / fibrinolysis.
|
|
|
Situations that FDP need to be tested
|
where there is an imbalance in clotting / fibrinolysis. Condition such as DIC, Liver disease, DVT, PE.
|
|
|
What is coagulation police
|
it is serine protease inhibitors to inhibit coagulation. To stop clotting too much.
|
|
|
why serine protease inhibitors is needed
|
it is needed if thrombin is made without regulation,
|
|
|
Specific inhibitors of coaguation are that serine protease inhibitors.
|
AT( antithrombin), Heparin cofactor II, Alpha 2 macroglobulin, TFPI ( tissue factor pathway inhibitor), Protein C and Protein s that are cofactors, FDP's from fibrinolysis.
|
|
|
Antithrombin inactivates
|
thrombin, Xa, XIa, XII a.
|
|
|
Antithrombin activity enhanced by
|
heparin - heperan therapy depends on AT levels.
|
|
|
Antithrombin inhibits
|
plasmin and activators casue inhibits fibrinolysis and kallekrein.
|
|
|
Heparin cofactor activity and inhibition
|
it inhibits thrombin cause coagulation inhibitors. Activity is multiplies when heprain bound.
|
|
|
Alpha 2 Macroglobulin
|
inhibits several facros such as KALLEKREIN cause coagulation inhibition
|
|
|
TFPI - tissue factor pathway inhibitor factors
|
inactivates factors VII a, Xa.
|
|
|
Protein C and S inhibits factors
|
inhibits coagulation factos Va and VIIIa
|
|
|
Protein C and S are depend on
|
Vitamin K dependent
|
|
|
Protein C and S enhases
|
fibrinolysis. - dissolve clot - inhibit coagulation
|
|
|
Protein C and S requires what in endothelial cell
|
thrombomodulin in endothelial cells.
|
|
|
Purpose of Fibrinolysis police
|
to limit the process in inhibitors of fibrinolysis - Stop too much clotting dissolving
|
|
|
IF too much fibrinolysis
|
FDP's act as anticoagulation and cause excess bleeding .
|
|
|
Special inhibitors in fibrinolysis
|
PAI ( plasinogen activated inhibitor) 1, 2, and 3 , Alpha 2 macroglobulin, A 2 antiplasmin, TAFI - thrombin activatable fibrinolysis inhibitor.
|
|
|
Procoagulators that produced by alpha granuales help to prevent early clot dissolving.
|
PAI ( plasinogen activated inhibitor) 1, 2, and 3 , Alpha 2 antiplasmin.
|
|
|
One inhibitor that inhibits in fibrinolysis and coagulation.
|
Alpha 2 macroglobulin
|
|
|
laboratory methords to evaluate coagulation and fibrinolysis inhibitors
|
measure protein by elisa or RIA, Functional assay to assess inhibitor function, chromogenic substrate assays,
|
|
|
Antithrombin functional assay principle
|
to measure inhibitor activity aganist thrombin or Xa. Antithrombin neutralises portion of active factor
|
|
|
Laboratoey methords to evaluate fibrinolysis
|
Measurment of proteins, measure of lysis products.
|
|
|
measurment of proteins incude in evaluate fibinolysis.
|
measurment of plasminogen levels, and plasminogen activators cush as TPA.
|
|
|
ways to measure protein - plasminogen levels to evaluate fibrinolysis.
|
by RID and Chromgenic substrate. RID measures antigen levels, Chromogenic sustrate measures function.
|
|
|
Principle on Chromogenic substrate assay to measure plasminogen level in evaluate fibrinolysis
|
add plasminogen activator to patient plasma cause production of plamin. Plasmin is added to as sysnthesised sunstrate cause production of color. Color is proportional to plaminogen concentration. Result is reported as % of normal usuing standard activity curve from referance plasma.
|
|
|
ways to measure lysis product to evaluate fibrinolysis
|
by D-dimer testing, FDP testing. And euglobulin lysis test
|
|
|
Principle on FDP testing
|
to measure lysis products to evaluate fibrinolysis. Do the latex agglutnation test. If postive do the titer on serum.
|
|
|
FDP testing detects fagment of
|
of both fibrinogen and fibrin. So not specific for in vitro fibrinolysis.
|
|
|
Coagualtion tubes for FDA testing
|
they are commercially avialable, tubes that contain thrombin, tube has trypsin inhibitor, repsilase
|
|
|
purpose of tube contain thrombin in FDP testing
|
to insure complete clotting, to avoid false postive if leftover firinogen is present.
|
|
|
purpose of tube contain trypsin inhibitor in FDP testing
|
to neutralize plasmin, and inhibits in vitro fibrionolysis,
|
|
|
what to do if patient on heparin in FDP testing
|
use reptilase
|
|
|
intrepert positive result on PDP testing
|
patient has increased level of fibrinolysis or increased level of fibrigenolysis. In conditions such as DIC,PE,MI alcoholics etc
|
|
|
False postive on FDP testin
|
in rheumatoid factor, or if sample is not clotted completely.
|
|
|
purpose of D dimer testing
|
to measure crosslinked fibrin fragments- that are actual brakdown of on vivo clots. Very specific.
|
|
|
methords to do D dimer testing
|
latex agglutnation and EIA- elisa immuno assay.
|
|
|
intrept positive and false positive result in D dimer testing conditions
|
positive in DIC, PE, and other. False postive in RA.
|
|
|
Euglobulin lysis test priciple
|
to compare patient clot lysis with normal clot lysis in test tube.
|
|
|
euglobulin result range for normal and abnormal
|
normal is > 2 hours fo clor to lyse. < 2 hours mean patient has increased fibrinolysis,
|
|
|
procedure for euglobulin test
|
isolates the euglobulin factors of plasma. One tube with no inhibitors of fibrinolysis, and other tube contain fibrinogen, plasminogen, and plaminogen activators. Fraction is clotted with trombin then allowed to lyse.
|
|
|
one test to diffrentiate fibrinolysis and fibrinogenolysis , and expencted result
|
by D-dimer test. Postive on fibrinolysiss and negative on fibrinogenolysis. All other tests such as FDP, euglobulin lysis are postive for both fibrinolysiss and fibrinogenolysis.
|
|
|
Additional/ confomatory coagulation testing you can perform
|
mixing studies, single factor assay, factor XIII level, reptilase time, pathologic inhibitor assay, vonWillebrands assays.
|
|
|
Purpose of mixing studies
|
to differenciate heriditory factor dificiences from acquired pathologic inhibitors.
|
|
|
Procedure for Mixed studies
|
abnormal PT and aPTT is repeated with 1:1 plasma patient and nomal pooled plasma and see if the test corrected ot with in referance range.
|
|
|
how to determine facter deficiencies in mixed study
|
reperated test will correct patient result.
|
|
|
in mixed study, how is PT or aPTT is corrected
|
50% of the factor activity can supply through the normal pooled plasma can correct PT or aPTT
|
|
|
How to report positive mixed study result
|
as corrected PT or correct aPTT.
|
|
|
when is single factor assay is performed.
|
if there is a factor dificency that suggested by tests screening and mixed studies
|
|
|
test you have to do before performing single factor assay
|
screening tests such as PT and aPTT, mixed studies.
|
|
|
level of a factor in a patient is expresed as
|
percent of factors.
|
|
|
Single factor procedure, standard factor activity curve methord
|
make dilution fo NPP ( normal pooled plasma). Dilution are mixed with patient plasma that has factor deficent. Mixture run as PT or aPTT, time of clot for each dilution is recorded. Each dilution reperent a % of factor activity, polt is made on 2 X 3 cycle log with time vx % factor activity.
|
|
|
Single factor procedure, patient activity curve methord
|
make dilution of patient plasma, each dilution mixed with factor deficient plasma. Run PT or aPTT on each mixture. Time to clot is recorded. Time to clot is compared to standard curve. Actual % factor activity is calculated.
|
|
|
Normal values for single factor assay
|
50- 150% activity
|
|
|
diadvantages of single factor assays
|
reagents are expensive, need automaded instruments, technically dificult.
|
|
|
When is facter XIII testing done?
|
when fibrin stabilizing facter is fecicant which cause excess bleeding sometime after initial clot.
|
|
|
qualitative testing for facter XIII
|
clot solubulity testing.
|
|
|
Procedure for clot solubulity testing.
|
Mix patient plasma and thrombin = clot. Incubate 30 minture in 37 C and remove clot by washing in saline. Incubate another 24 hours in testbube with 5M urea or 1% monochloroacetic acid and look for clot. If clot formed - it’s a postive test. If clot dissolved - les than 1-2% facter XIII activity.
|
|
|
Intrepert the result for clot solubility test
|
If clot formed after 24 hours of washing with saline - it’s a postive test. If clot dissolved - less than 1-2% facter XIII activity.
|
|
|
Quantitative testing for facter XIII
|
Elisa, not often requested, and not in widespread use.
|
|
|
Compare repilase time test and thrombin time test
|
both are similar expect reagent is reptilase instead of diluted thrombin. Warm the reagent, and add patients PPP and report the time to clot.
|
|
|
Procedure for replilase time test
|
Same as thrombin time exept replilase is the reagent. Warm the reagent, and add patients PPP and report the time to clot.
|
|
|
Advantage of using reptilase time test
|
it is not affected by heprain while thrombin time is. , Also, minimally affected by FDPs that is an anticoagulation.
|
|
|
repeated screening test PT and aPTT for mixed and did not corret the result suggests that
|
pathologic inhibitors that can be acquired antibodies.
|
|
|
Types of pathologic inhibitorsin that shown in mixed study
|
two type, one that bind and inactivate a specific facotor, or one that bind phospholipids in the clotting process = antiphospholipid antibodies.
|
|
|
Immediate acting inhibitors result
|
its is when there is no correction or modified correction.
|
|
|
Immediate acting inhibitors example
|
Lupus like antibodies or antipospholipid antibodies.
|
|
|
Slow rectiing inhibitors charectorestics
|
result in immidiate correction, but further incubation cause prolonged clotting time.
|
|
|
Slow rectiing inhibitors examples
|
facter VIII inhibitors.
|
|
|
Types of antiphospholipids antibodies that can be an inhibitors
|
LLAC - lupus like anticoagulant, ACLA -Anti cardiolipin antibodies, DVT , reperated pregnancy loss.
|
|
|
screen for antiphopholipid antibodies test
|
can use aPTT, or a specific screen methods for aPL ( antiphospholipid) such as tissue thromboplastin inhibitation test, dilute russell's viper venone test, Kaolin clotting time. Mixed studeis shows no correction or modified correction.
|
|
|
specific screen methods for aPL ( antiphospholipid) antibodies such as
|
tissue thromboplastin inhibitation test, dilute russell's viper venone test, Kaolin clotting time.
|
|
|
conformotory tests for antiphopholipid antibodies
|
clot-based for LA, Immunoassay for APL.
|
|
|
most common single facotrs that is acquired inhibitors of coagulation factors.
|
anti Factor VIII and anti factor IX.
|
|
|
common antiphospholipid antibodies that associated with acquired inhibitors of coagulation factors
|
SLE, Autoimmune disease cancers, infections, drug reactions.
|
|
|
charectorestics of vonWillebrand Factor
|
they required platlet adhesion, is part of factor XIII complex, so part of primary and secoundary hemostasis.
|
|
|
how to test for vWF activity
|
by adding platlets and ristocetin, by performing modified platlet aggregation study.
|
|
|
theory on modified platlet aggregation study or RIPA- risrocetin included platlet aggregation
|
by performing restocetin co-factor assay to see if patient vWF ability to bind with patient GPI Ib/IX platlet receptor.
|
|
|
referance range for ristocetin cofactor assay
|
60 -180%
|
|
|
methords to test for vWF protein testing
|
by immunological methords such as laurell rocket assay, or ELISA.
|
|
|
vWF protein testing for
|
for typing of vonwillsbrand's disease.
|
|
|
methords to test for vWF multimers
|
by electrophoresis. It required for typng vWF
|
|
|
purpose to teest for vWF multimers
|
It required for typng vWF
|
