Exam 2 Flashcards
Define thrombosis, deep vein and pulmonary embolisms
development of a blood clot in the veins or arteries that obstruct blood flow and cause tissue death
deep vein-not moving
PE-moving clot
What stage of coagulation do antiplatelet and anticoagulant drugs suppress or affect
anticoagulants- 2ndary
antiplatelets- 1ary
What could happen if antithrombotics are overused
uncontrolled bleeding, can be fatal
Which are arterial and which are venous thrombosis acute myocardial infarction deep vein thrombosis ischemic cerebrovascular accident pulmonary embolism
acute myocardial infarction- AT
deep vein thrombosis-VTE
ischemic cerebrovascular accident-AT
pulmonary embolism-VTE
How does coumadin work
it is a vitamin K antagonist, it slows the activity of the enzyme that reduces vitamin K
What are the vitamin K dependent factors?
II, VII, IX , X, proteins C, S and Z
What is the goal of coumadin therapy
reduces but does not eradicate thrombin generation.
In what order to the factors affected by coumadin decrease?
VII, because it has the shortest half life
IX
X
prothrombin
What are the risks of coumadin, how quickly does it start to affect coagulation?
cannot be taken during pregnancy
begins immediately, it takes 5 days for the factors to reach the correct therapeutic levels
patient is at risk of thrombosis, cannot take any anticoagulants
What happens if you take anticoagulants while also undergoing coumadin therapy?
can increase risk of skin necrosis
What tests are used to monitor coumadin therapy, what pathways are they monitoring
Prothrombin time- measures how extrinsic and common pathways are affected
What reagents are in prothrombin time (PT) test
tissue factor, phospholipid, ionic calcium- creates extrinsic tenase
What will happen to PT results during coumadin therapy
will be prolonged very soon because of short half life of factor VII
What is the INR sometimes added to PT
international normalized ratio, accounts for variations in thromboplastin reagents
What is the INR therapeutic range for a patient on coumadin?
2-3
What is the INR range for a patient with a mechanical heart valve?
2.5-3.5
What does an INR of over 5 mean?
increased risk of hemorrhage, critical result
What can be used it the PT test is compromised?
Chromogenic factor X assay
it inhibits any substances that could affect the test results
if patient has taken any other anticoagulants, inhibitors or have any deficiencies
What could a patient do to affect their coumadin therapy negatively? How are the test results affected?
cannot eat too much vitamin K, it decreases coumadin’s effectiveness
reduces INR
What is coumadin sensitivity and what causes it
gene mutations that affect vitamin K or affect enzymes that breakdown coumadin
makes patient react to smaller amounts of coumadin, must be given lower dosage
What is coumadin resistance and what causes it
if the coumadin receptors on patients cells are insufficient, makes coumadin useless and patient will less responsive to it
less effective, patient needs higher dosage
How can coumadin be reversed? What if its severe.
if overdose and excessive bleeding occurs,
patient will be given oral or IV vitamin K
if severe- patient needs substitute active coag factors from blood products like plasma
How does UFH work?
unfractionated heparin- made of polysaccharides that binds to plasma antithrombin and activates it.
new complex binds to and inactivates serine proteases IIa (thrombin), IXa, Xa and XII
stops clotting by activating antithrombin
What tests are used to monitor heparin therapy
PTT- partial thrombinplastin time and platelet count
Chromogenic anti-Xa assay
Activated clotting time
What side effects can heparin have and how can they be affect test results
platelet count is 40% lower, heparin induced thrombocytopenia
What conditions can lead to heparin resistance
inflammation
prolonged UFH therapy
platelets release platelet factor 4 which neutralizes heparin (shortens PTT)
What can cause falsely prolonged PTT levels
hypofibrinogenemia, factor deficiencies, present of LAC, FDP or paraproteins
What are the limits of chromogenic anti-Xa assay? and activated clotting time?
only reflects Xa binding to antithrombin, PTT is better because it gives a global impression
ACT- only for point of care and cardiac surgeries
What is the median ACT interval
98 seconds
How can we reverse the effects of heparin
protamine sulfate- from salmon perm, binds and neutralizes heparin
also fibrinolytic therapy
How does LMWH work
low molecular weight heparin
also a pentasacharride that binds antithrombin but shorter
less bridging, mostly Xa inhibition
Which heparin therapy is best at activating antithrombin? and Xa?
UFH-antithrombin
LMWH- Xa
What tests are used to measure LMWH
chromogenic anti-Xa assay,
not PTT because it mostly affects Xa
What does the chromogenic anti Xa heparin assay measure
measures leftover products and substrates after Xa is inhibited, the more substrates and products the less heparin present
What is fondaparinux and how does it work
synthetic formula of pentasacharride in UFH and LMWH
short like LMWH only inhibits Xa
raises antithrombin activity by 400
What test is used to measure the effectiveness of fondaparinux?
chromogenix anti Xa heparin assay
not PTT
How can fondaparinux overdose be reversed
rFVlla- can particially reverse effect
What are DTIs and what do they do
direct thrombin inhibitors
anticoagulants that dont need antithrombin to work
binds both free and clot bound thrombin
What lab tests are used to measure DTI effectiveness and how are they affected by it.
prolongs Thrombin time and PTT
Ecarin chromagenic assay- snake venom
plasma diluted thrombin time- patient plasma + normal plasma
What are intravenous DTIs and give examples
How do they affect test results
argatroban and bivalirudin
used on patients with HIT
binds and activates free or clot bound thrombin
prolong everything
What tests are used to monitor intravenous DTIs
PP, PT, PTT and ACT
all prolonged
What is DOAC and how is it monitored, name the drug
Direct oral anticoagulants
no monitoring needed, no antithrombin needed, acts directly on X
prolongs PTT, TT and ECT
Dabigatran
What do intravenous antiplatelet drugs do and what are they for
block fibrinogen or VWF from binding, reducing platelet aggregation
for percutaneous coronary intervention
primary hemostasis
What are intravenous antiplatelet drugs coadministered
UFH and aspirin
What kind of drugs are these
abciximab( ReoPro) , eptifibatide (integrillin) ,tirobaban hydrochloride ( Aggrastat)
Intravenous antiplatelet drugs
What kind of drugs are these Aspirin clopidogrel prasugrel ticargrelor
oral antiplatelet drugs
What mechanism do antiplatelet drugs use
bind to ADP receptor on platelets (P2Y12) and suppress their aggregation
What is aggregometry
reference for antiplatelet drugs
What are the platelet counts for PPP and PRP and what do they stand for?
PPP- poor platelet count less than 10,000
PRP platelet rich plasma about 200,000
What sodium citrate to blood volume ratio should there be if the HCT is elevated 55% or more
9:1 ratio
must compensate to avoid falsely prolonged results, there is too much anticoagulant vs coagulation factors if this discrepancy is not adjusted
What is the formula for sodium citrate adjustment for elevated HCT
C=(1.85x10^-3)(100-HCT)V
C= citrate volume ml
V= volume of whole blood
HCT= hematocrit in %
Describe how each of these affect test results short draw specimen clot visible hemolysis lipemia or icterus tourniquet >1min specimen @ 1-6C specimen @ >25C
short draw- PT and PTT false prolonged
specimen clot-unacceptable
visible hemolysis-unpredictable results
lipemia or icterus-optical instruments cant see through color
tourniquet >1min- elevated VWF and fibrinogen, falsely short clot results
specimen @ 1-6C-precipitation of VWF multimers, activation of plts, VII, destruction of plt integrity
specimen @ >25C- deteriorates V and VIII
How should hemostasis specimen be transported and stored
15-25C, ambient
because coag factors are heat labile (unstable)
PT- within 24hrs
PTT within 4 hrs
When should coag specimen be spun down
within 1 hour if patient of UFH or if specimen can’t be resulted quickly -> plasma can be frozen, tested within an hour of thawing
How soon should these specimen get tested PT no UFH PTT no UFH PT with UFH Factor assay optical platelet aggregometry whole blood aggregometry
PT no UFH- within 24hrs PTT no UFH- within 4hrs PT with UFH- spin in 1 hr, test in 4hrs Factor assay-4hrs optical platelet aggregometry-spin in 30min, test in 4hrs whole blood aggregometry-4hrs
What is the bleeding time test? What is the normal range and what does it mean if it is prolonged
not used anymore- patient was cut, wound blotted every 30s, duration of bleeding was measured,
2-9 min
prolonged-functional platelet disorder, vascular disorder
How is platelet PRP aggregometry performed
with PRP-light transmittance, near 0% transmittance
agonist added as platelet activator
intensity of light transmitted increases at first then increases as more aggregation occurs
more platelet aggregation makes more light pass through PRP,
should be 40% +
if low, platelet function deficiency
What are the 5 steps of platelet aggregation
resting platelet stable baseline shape change primary aggregation secretion secondary aggregation
How is whole blood platelet aggregometry preformed
measures electrical impedance
platelets adhere to an electrode and impede a current
if impedance rises, platelet aggregation is rising, charge goes down
How does platelet lumiaggregometry work
measures the secretion of ATP by platelets
luciferin-luciferase reagent creates cold chemiluminescence proportional to ATP
amplifies luminescence
What is an agonist
used in platelet test for specific membrane binding sites on platelets
List the platelet agonists that used to activate platelets in aggregometry
Thrombin TRAP-thrombin receptor activating peptide ADP Epinephrine Collagen Arachidonic acid Ristocetin
What specific deficiencies are arachidonic acid and ristocetin for
arachidonic acid-deficiencies in eicosanoid synthesis pathway
Ristocetin- abnormalities of VWF in VWD
Match the agonist to the binding site:
Agonists: thrombin, arachidonic acid, collagen, epinephrine, ADP, TRAP
Binding sites: alpha adrenergic, PAR1 and PAR2, GPIa/IIa and GPVI, thromboxane receptor
- Thrombin- cleaves PAR-1 and PAR-2
- ADP- binds P2Y1 and P2Y12
- Epinephrine- binds alpha-adrenergic receptors
- Collagen-binds GPIa/IIa and GPVI, no primary aggregation
- Arachidonic acid-becomes thromboxane A2 binds thromboxane receptor
What are these abbreviations for
PT, PTT, FGB, TCT, ACT
prothrombin time, partial thromboplastin time, fibrinogen, thrombin clotting time, activated clotting time
finds coagulopathies- coag deficiencies
What reagent is used in PT test?
What is the normal range?
What pathway does it monitor?
What factor is first activated?
thromboplastin: TF +phospholipids +Ca
12.6-14.6
Extrinsic pathway, and common
Factor VII
IF a PT test is prolonged, what is the most likely reason?
What is PT used to monitor?
VII deficiency, V and X, FBG, insensitive to VIII, IX and XIII
Coumadin monitoring
What is the PT procedure
What can PT diagnose
Thromboplastin+ PPP, timed until clot forms
multiple deficiencies in LIVER, vitamin K, cause prolonged PT
How can we tell if a PT test is prolonged due to liver disease vs vitamin K deficiency
only factor VII is reduced when its a vitamin K deficiency
both reduced in liver disease
What is the reagent in a PTT test?
What pathway does it measure?
What does it monitor?
What is the normal range?
reagent- phospholipid + neg charged activator like silica
intrinsic pathway via contact with neg charged surface
monitors UFH
26-38 normal
60-100 if on UFH
What factors prolong PTT, which ones don’tW
all deficiencies prolong it except for VII and XIII
What can prolong a PTT other than coag factors
antibodies against coagulation factors, nonspecific inhibitors and interfering substances, could be vitamin K deficiency
What is the normal range for a TCT
What reagent is in TCT and what does it cleave?
Also called TT
15-20s
reagent bovine thrombin- cleaves fibrinopeptides A and B-> forms detectable fibrin polymer
Does TCT give qualitative or quantitative fibrinogen measurements
What are the possible results?
What is it used to monitor
both qualitative and quantitative
afibrinogenemia, hypofibrinogenemia ( <100)
dysfibrinogenemia- abnormal fibrinogen
monitors UFH to confirm prolonged PTT, can also find direct thrombin inhibitors
What factors cause TCT to become prolong?
Which ones don’t
fibrinogen, thrombin
not XIII nor anything before thrombin
What is the purpose of performing a mixing study?
to detect LACs and distinguish them from specific inhibitors and factor deficiencies
What is an LAC? How can they affect lab tests
lupus anticoagulants- IgG immunoglobulins directed against phospholipid-protein complexes
NON SPECIFIC INHIBITORS-prolong PTT
What are factor inhibitors? Why do they arise?
IgG immunoglobulins directed against specific coag factors
arise in response to factor concentration treatment,
What is the most common specific inhibitor, what disease is it associated with?
anti factor VIII, hemophilia
Name the tests involved in a mixing study
prolonged PTT/PT-> prolonged TCT
Mixing study- patient plasma + platelet poor normal plasma (PNP)
corrected mix-> factor deficiency
uncorrected mix-> incubated mix
uncorrected incubated->inhibitor if bleeding
LAC if not bleeding
corrected incubated->factor deficiency
Explain how a fibrinogen assay works
PPP 1:10 with Owren buffer
bovine thrombin to diluted specimen
FBG turns into fibrin
What is the normal range for a fibrinogen assay
The __ FBG present the ____ the time it takes to form a clot
220-498
more FBG
lower time
Name the reference ranges for high and low fibrinogen assays and what they might indicate
low-<200- liver disease
high>498 liver disease, pregnancy, chronic inflammation
afibrinogenemia- anatomic hemorrhage
What is a single factor assay and when is it used?
after prolonged PTT but normal PT and TCT
mixing study if corrected after incubated and single factor deficiency is suspected
What are the 3 factor deficiencies that accompany hemorrhage and what hemophilia are each associated with
VIII- most common, hemophilia A
IX- hemophilia B
XI- Rosenthal
What is the purpose of the Nijmegan-Bethesda Assay
confirms and quantifies anti-factor VIII inhibitors
What likely causes a PTT and PT to be prolonged but the TCT to be normal?
some single factor deficiency of the common pathway
deficiency of prothrombin, V or X
What are factor XIII assays used for
if PT and PTT are normal but there is a factor XIII deficiency
poor wound healing, oozing wounds
What are the fibrinolysis assays
D-Dimer Immunoassay-increased with DIC, systemic fibrinolysis, DVT, PE
Fibrin degradation product immunoassay-measures fibrin split products
Plasminogen Assay-hyper-too much clot degradation (trauma, inflammation), hypo-not enough
Tissue Plasminogen Assay: increased- fibrinolysis, inflammation, pregnancy, decreased: thrombolytic therapy, hepatitis, cancer
Plasminogen activator inhibitor- decreased: MI, stroke, DVT risk, increased: thrombosis
What are the 6 endpoint detection principles of coagulation in the lab
mechanical- 2 metal electrodes in plasma or steel ball
photo-optical- optical density during clotting
nephelometric-forward angle light scatter
chromogenic- uses chromophore to measure specific coag factors
immunologic- antigen-antibody reactions measured with light absorbance
viscoelastic- global hemostasis assessment, whole blood clotting
What type of tests measure the entire coag cascade and are therefore not very specific
clot-based tests
What tests are isolated to specific enzyme reactions
chromogenic tests
What tests are affected by icterus/lipemic specimen? Which ones are not
affected- photo-optical
not affected- clot based
When can POC test instruments be utilized
during clinical procedures or surgeries
bedside
self testing
infants
What tests can POC instruments run
ACT-activated clotting time- for heparin monitoring during cardiac surgery
PT/INR-for monitoring coumadin
What specimen is used in TEG tests?
What is being measured?
Adv and Disadv
whole blood clot formation
measures entire kinetic process of clot formation
adv: evaluates everything else in blood WBCs, proteins, coag factors
disadv: operator dependent, need training, high skill
