Final Flashcards
This is defined as an alteration in the coagulation system that predisposes a person to form clots:
Hypercoagulability
____ in US suffer from blood clots per year, with a __% mortality rate:
> 200k
30% (most due to PE)
In order for thrombosis to present clinically, at least __ risk factor needs to be present to overcome the natural ____ to protect against clot formation:
1
inhibitory process
List the 3 types of natural plasma inhibitors of coagulation factors:
- Serine-protease inhibitors
- Protein C
- TFPI (tissue factor pathway inhibitor)
List the two types of Serine-protease inhibitors:
- AT (anti-thrombin)
* HC-II (heparin cofactor II)
Combining __ with AT increases it’s effectiveness 200x:
heparin
AT is synthesized in the ___ and has a half life of ___ days:
liver
2-3 days
____ is a major inhibitor of 2a and 10a:
AT
7a, 11a, and 9a also somewhat inhibited
AT deficiency is autosomal __, occurs mostly between ages ____, and results in ___:
dominant
15-35
clotting
List some causes of acquired AT deficiency:
- liver disease
- consumption coagulopathy
- Renal disease protein loss
- continued heparin use
HC-II is a minor inhibitor of ___:
Thrombin
The major inhibitor of thrombin is ___, and the minor inhibitor is ___:
major: AT
minor: HC-II
Does HC-II inhibit any other coag factors besides thrombin:
No
With HC-II, you need a ____ concentration of heparin to inhibit thrombin:
higher
Symptoms of HC-II deficiency range from ___ to ___:
asymptomatic
venous/arterial thrombosis
Which has a higher affinity for heparin, AT or HC-II:
AT
which is why HC-II requires more heparin to affect tests
Protein C is activated by ____, which is found in _____, and it is regulated by___:
- Activated by: Thrombomodulin, found in epithelial cells
* Regulated by: 5a
___ degrades factors 8a and 5a:
Protein C
Protein C inactivates _____:
PAI-1
____ inactivates PAI-1:
Protein C
Increased 5a ____ Protein C activation, while decreased 5a ___ Protein C activation:
- more 5a= enhances
* less 5a= inhibits
Is Protein C Vit K dependant:
yes
Protein C deficiency is among the most common causes of______ :
hypercoagulability
Protein C deficiency is autosomal ___ and affects ___% among those with inherited venous thrombosis:
- dominant
* 6-10%
List some causes of acquired Protein C deficiency:
liver disease
DIC
warfarin therapy
Severe infection/shock
How is Functional Protein C activity tested for:
- mix pt plasma w/ PC def plasma
- Run APTT
- if it corrects: no deficiency
List the two lab tests used to check for Protein C activity/deficiency:
- Functional PC Activity
* Antigen Assay
___ is used to determine the mechanism of deficiency (decreased production OR abnormal protein) in testing for Protein C:
Antigen Assay
Protein S exists in these two forms:
- Free form (40% of total PS, acts as cofactor to active PC)
* Bound form (C4b-Bp)
_____ exists in a free form and a bound form, with the free form making up 40%:
Protein S
List some causes of Acquired Protein S Deficiency:
coumadin therapy & L-asparaginase Pregancy Oral contraceptives Low Vit K levels liver disease DIC
T/F
Deficiency of TFPI has yet to be associated with thromboembolitic disease:
True
____ may play a significant role in preventing clot formation, though a deficiency of it has not yet been associated with thromboembolitic disease:
TFPI
TFPI inhibits 9a and 10a by binding __ and __:
7 and 3
___ inhibits 9a and 10a by binding 7 and 3:
TFPI
TFPI inhibits __ and __ by binding __ and __:
- inhibits: 9a and 10a
* by binding: 7 and 3
TFPI + 7 + 3 inhibits ___ and __:
9a and 10a
HIT/HIIT is due to an antibody to ___:
heparin-PF4 complex
Lipoprotein a (LPa) inhibits fibrinolysis by competing with ___ for binding with ___:
fibrinogen
fibrin
LPa binds __ and ___:
- fibrinogen (blocking fibrin from binding)
* TPA
Prothrombin Nucleotide ______ Mutation increases prothrombin level and DVT risk:
G20210
_____Mutation increases prothrombin levels and increases DVT risk:
Prothrombin Nucleotide G20210 Mutation
T/F
Hyperhomocysteinemia is a risk factor for DVT:
True
__% of those with dysfibrinogenemia have recurring ___:
20%
clots`
Unfractionated Heparin therapy is monitored via ____, and extended use can lead to ____:
APTT
HIT/HITTS (heparin-PF4 Ab)
____does not require monitoring since it is cleared by the kidneys:
LMWH
LMWH does not require monitoring since it is cleared by the __:
kidneys
Asprin, Plavix, and Pradaxa are all ____ agents:
anti-platelet
Both alternative anticoagulants- Hirudin is from ____, Danaparoid is similar to LMWH except there is no ___ available:
leeches
antidote
Aspirin is an ____ agent that works by inhibiting ___, which deactivates ___:
anti-platelet
cyclo-oxygenase
TXA2
Plavix is an ____ agent that works by inhibiting ____:
anti-platelet
inhibits ADP binding
Pradaxa is an ___ agent that works be inhibiting _____:
Thrombin
T/F
Unfractionated heparin therapy is monitored via PT:
False, it is monitored via APTT
___ is similar to LMWH, except there is no antidote available:
Danaparoid
___ is the inactive form of Plasmin:
Plasminogen
____ is the enzymatic dissolving of fibrin clot:
fibrinolysis
___ works by breaking down polymer bonds and release FDP’s:
Plasmin
___ is the key enzyme in fibrinolysis:
Plasmin
List the two forms of Plasminogen:
- Glu- Plasminogen
* Lys- Plasminogen
Plasminogen is synthesized in the __, has a half life of __, a plasma content of __mg/dL, and comes in _ forms:
- liver
- half life~ 2 days
- 20mg/dL
- 2 forms (Glu and Lys)
Which form of Plasminogen is more readily converted to active plasmin by activators:
Lys
____ is capable of being cleaved, results in lysine as new terminal amino acid:
Glu-Plasminogen
Glu-plasminogen becomes extended when bound to ___:
fibrin
List the 4 endogenous plasminogen activators:
- Urokinase
- t-PA
- Scu-PA
- Other
List the two exogenous plasminogen activators:
- Urokinase
* Streptokinase
The primary source of plasminogen activators are in the _____:
blood vessel endothelium
____ is the primary plasminogen activator in the GI system:
Urokinase
Levels of ___ fluctuate rapidly in response to exercise, venous occlusions, alcohol and drugs, DDAVP, and steroids:
t-PA
If patient shows no increase in t-PA activity, they are at an increased risk for ___:
DVT
Scu-PA has a half-life of __mins and is rapidly inhibited by __:
5-10 mins
PAI-1
T/F
Other sources of plasminogen activation inlcude: initation of coag contact factors 11a and 12a, kallikrein, and HMWK:
True
Is urokinase an endogenous or exogenous plasminogen activator:
both
List the 3 drawbacks for use of Urokinase (u-PA):
- expensive
- lower affinity for fibrin than t-PA
- commonly develop hypofibrinogenemia
Which has a higher affinity for fibrin, u-PA or t-PA::
t-PA (which is one reason why it is used as a therapeutic fibrinolytic agent)
Streptokinase is not an ____, it is derived from ___:
not an enzyme
derived form Streptococci
___ forms 1:1 complex with plasminogen which exposes an active serine site:
Streptokinase
The major drawback of _____ is that it can create immune response with Ab development:
Streptokinase
___ is the primary substrate of PAI-1:
t-PA
Regulation of fibrinolysis is dependent on the interaction of t-PA with ____:
PAI-1
Excess of PAI-1 is associated with ____, and risk is significantly higher in patients w/ MI <45 years old:
thrombotic disease
T/F
PAI-1 is an acute phase reactant:
True
_____ is synthesized by blood vessel endothelium and released in inactive state, is an acute phase reactant, and it’s primary substrte is t-PA:
PAI-1
Where is PAI-1 synthesized:
blood vessel endothelium
is released in inactive state, must interact with t-PA
Plasmin has a half life of ___:
seconds
Plasmin degrades both ___ and ____:
- fibrin clots
* native fibrinogen
Fragment X is composed of _ and _ fragments:
Y and D
think D-E-D monomer
Fragment Y is composed of _ and _ fragments:
D and E
___ is cleaved cross linked fibrin:
D-dimer
Y and D fragments make up __:
Fragment X
D and E fragments make up __:
Fragment Y
___ degrades both fibrin clots and native fibrinogen:
Plasmin
Plasmin products have an ___ effect on coag system:
inhibitory
Alpha 2-antiplasmin inhibitor forms a 1:1 complex with ___:
plasmin
Plasmin forms a 1:1 complex with ___, which protects it from inhibitor by binding to same site as inhibitor, therefore inhibitor cannot bind and ____ proceeds:
alpha 2-antiplasmin inhibitor
clot lysis
With alpha 2-antiplasmin inhibitor, plasmin activity is limited to area of ___ deposition:
fibrin
Alpha 2-macroglobulin, C1 inactivator, and alpha 1-antitrypsin are all ______:
plasmin inhibitors
Only 3 cases of congenital ___abnormalities have been reported:
Plasminogen
Low levels of t-PA = recurrent ___:
clotting events
Alpha 2-antiplasmin inhibitor = severe ____ tendency:
hemorrhagic
Alpha 2-antiplasmin inhibitor is bound to fibrin by ___:
8a
RVVT is used to differentiate __ from ___ deficiency:
8 from 10
In RVVT, you substitute venom for ____:
tissue thromboplastin (venom does not require F7)
Increased Stypven time points to a deficiency in one of these three factors:
*10, 5, 2
Stypven time would be ___ in a F7 deficiency:
normal
___ cleaves A & B peptides:
Fibrin
Fibrin cleaves A/B peptides, leaving fragment___, then factor__ causes them to polymerize, giving crosslinking that forms ____:
- X (D-E-D monomer, or Y+D)
- F13a
- fragment Y (D-E)
The principle of the FDP test is latex particles coated with Ab’s to human fibrinogen _____fragments:
D and E
T/F
Serum is used for FDP, while Sodium citrate is used for RVVT:
True
Normal D-dimer level is
1
Does the D-dimer test detect breakdown products from both cross-linked fibrin AND fibrinogen:
No. Only cross-linked fibrin
Thrombin+TM+Protein C =
APC (Activated Protein C complex)
APC + Protein S =
powerful anticoagulant
inactivates 5a, 8a, PAI-1
APC + Protein S = a powerful anticoagulant that inactivates these three things:
5a, 8a, PAI-1
In the functional Protein C activity assay, protein C in plasma is activated by __, the amount activated is determined by rate of hydrolysis by substrate; amount of product released is ___ to amount of Protein C:
venom
proportional
What 3 thing make up the APC (activated protein C complex):
Thrombin
TM
Protein C
APC + ___= powerful anticoagulant that inactivates 5a/8a/PAI-1:
Protein S
Protein C needs _____ to inhibit 5a and 8a:
Protein S
In functional Protein S activity assay testing, there is a ___ relationship between Protein S and ____:
linear
clot time
Protein S values may be falsely low in samples with elevated ___ levels due to improper venipuncture, cold activation on storage, or clinical conditions:
F7a
Reference range for PT:
11.5-14 seconds
ISI allows for calibration of various ___ to an international standard:
thromboplastins
Reference range for APTT:
20-45 seconds
