Exam 2 Material Flashcards
Coagulation proteins in circulation that are inactive are called:
zymogens
What is the purpose of activated coagulation proteins:
interact to form fibrin clots, reinforcing the platelet plug
How were the coag proteins named:
based on sequence of discovery
All coag factors are produced in the ___:
liver
Factor 1:
Fibrinogen
Fibrinogen is Factor___:
1
Factor 2:
Prothrombin
Prothrombin is Factor__:
2
Tissue Factor is factor ___:
3
Factor 3 is ____:
Tissue Factor
Ionized calcium is factor___:
4
Factor 4 is:
Ionized calcium
Labile Factor is factor___:
5
Factor 5 is ____:
Labile Factor
Stable factor/proconvertin is factor___:
7
Factor 7 is ___:
Stable factor/proconvertin
Antihemophilic factor is factor___:
8
Factor 8 is ___:
Antihemophilic factor
Christmas factor is factor___:
9
Factor 9 is _____:
Christmas factor
Stuart-Prower factor is factor ___:
10
Factor 10 is ____:
Stuart Prower Factor
PTA is factor___:
Plasma Thromboplastin Antecedent
11
Factor 11 is ___:
PTA
Plasma Thromboplastin Antecedent
Hageman Factor is factor ___:
12
Factor 12 is ___:
Hageman Factor
FSF is factor___:
Fibrin Stabilizing Factor
13
Factor 13 is ____:
FSF
Fibrin Stabilizing Factor
Fitzgerald Factor is ______:
HMWK
HMWK is _____ factor:
Fitzgerald Factor
Fletcher factor is ____:
Prekallikrein
Prekallikrein is ____ factor:
Fletcher
What is the main substrate in the coag cascade:
fibrinogen
List the two cofactors of the coag cascade:
- Factor 5
* Factor 8:C
What do serine proteases do:
cut peptide bonds
Serine proteases include all but which factor:
Factor 8
_____ create cross linking in fibrin clot:
transaminases
_______ cut peptide bonds:
Serine proteases
Factor 8a is the only _____:
Transaminase
Contact proteins are only involved in initial phase of intrinsic activation and not consumed in normal clotting process, list the 4 of them:
11
12
Fitzgerald
Fletcher
Coumadin works ____, while heparin works _____:
Coumadin: in vivo
Heparin: in vivo and in vitro
List the Vit K dependent factors:
2,7, 9, 10
Protein C & S
PT is used to monitor ____ therapy:
Coumadin/Warfarin
Acquired Vit K deficiences most commonly seen in the following:
- post-surgical
- High dose antibiotic use
- liver disease
- malnutrition
List the fibrinogen or thrombin sensitive proteins (i.e. thrombin acts upon them):
1, 5, 8:C, 13
____ acts on factors 1, 5, 8:C, and 13:
Thrombin
_____ acts on all factors of in the fibrinogen group:
Thrombin
Which factors have positive feedback, procoagulant effects with Thrombin:
Factors 5 and 8
How is Factor 1 converted to soluble fibrin monomer:
Fibrinopeptides A & B are cleaved
Coag inhibitor binds to antithrombin (AT), and presence of heparin enhances this binding by how much:
200 times
______ has procoagulant and coagulation inhibiting effects:
Thrombin
The procoagulant effects of Thrombin rely on ___ feedback with Factors 5 and 8:
positive
The coagulation inhibiting effects of Thrombin binds to Thrombomodulin, via ___feedback with Factors 5a and 8a:
negative feedback
keeps clotting from getting out of control
Thrombin initiates tissue repair via these two mechanisms:
- induces chemotaxis
* stimulates proliferation of smooth muscle and endothelial cells
Which anticoagulants affect the extrinsic pathway:
coumadin/warfarin
test via PT
Why must calcium be added to a specimen to activate the coag cascade:
The citrate in a light blue top tube chelates the specimen calcium, so more must be added
Excess of PAI-1 is associated with _____:
thrombotic disease
higher in MI patients >45
The primary substrate of PAI-1 is ___, thus regulation of fibrinolysis is dependent on the interaction of ___ with ____:
t-PA
t-PA with PAI-1
T/F
PAI-1 is an acute phase reactant that is synthesized by blood vessel endothelium and released in an inactive state:
True.
BT would be ____ in fibrinogen disorders because ____:
normal
BT tests platelet function
_____ is a quantitative disorder causes by lack of synthesis in the liver:
afibrinogenemia
Levels of fibrinogen <100, generally asymptomatic:
hypofibrinogenemia
Abnormal structure and function of fibrinogen; qualitative disorder:
Dysfibrinogenemia
In dysfibrinogenemia, would BT and fibrinogen levels likely be normal:
Yes.
____ functions as a catalyst, forming bonds between proteins (fibrin monomers, fibronectin, collagen, alpha 2 inhibitor):
F13
___ deficiency is characterized by initial stoppage of bleeding, then recurrence of bleeding ~36 hours after event, low levels of this factor can be detected via ____:
Factor 13
5M urea test
List the 3 acquired disorders of secondary hemostasis:
- DIC
- Primary Fibrinolysis
- Liver disease
Why will the PT/APTT/ and TT be prolonged in DIC:
Due to consumption coagulopathy
What is the first and foremost treatment of DIC:
Remove stimulus!
then:
*LMWH, FFP, cryo
____ results from increased levels of plasmin:
Primary Fibrinolysis
What 3 things are normal in Fibrinolysis, but abnormal in DIC:
- d-dimer (high in DIC)
- Plt count (low in DIC)
- RBC’s (fragments in DIC)
Factor ___ has the shortest half-life:
7
You’d see a decrease in ___ factors in mild liver disease:
vit k dependent factors
Plt dysfunction, including decreased plt adhesion, abnormal plt aggregation to ADP, epi, and thrombin, and abnormal PF3 availability, occur in this acquired disorder of secondary hemostasis:
liver disease
Patients with ___ will present with diffuse hemorrhages due to increased plasmin fibrinolytic activity, where they actively form clots that will dissolve in a couple hours:
Primary Fibrinolysis
Pregancy, cancer metastases, promyelocytic leukemia would be____ causes of DIC:
Extrinsic
Events that damage vascular endothelium and expose collagen such as infectious diseases, snake venom, massive trauma/surgery would be ____ causes of DIC:
Intrinsic
_____ is seen in 1/ of chronic liver disease patients due to spleen sequestration secondary to congestive splenomegaly:
Thrombocytopenia
Congjugated estrogen can be used as a treatment for thrombocytopenia caused by ____:
liver disease
Hemophilia A is a deficiency of ____, and is the most common hereditary coag disorder:
Factor 8:C
Hemophilia A exhibits this type of inheritance:
X-linked recessive
Severe hemophilia A has F8:C levels of ____ and requires constant transfusion therapy of ___:
<1%
Factor 8 concentrates
Why is there an increased risk of developing alloantibodies or inhibitors to F8:C in Hemophilia A:
Due to regular F8:C infusions
Symptoms of alloantibodies to F8:C include:
hemarthrosis
hematuria
intracranial bleeds
hematomas
Why is a recombinant factor replacement preferred:
Risk of alloantibodies
In Hemophilia A, mixing studies do not correct with ____, which means either an inhibitor is present or reacting antibodies:
normal pool plasma
Which coag test will be abnorml in Hemophilila A:
APTT
prolonged if F8<20%
Also known as Christmas Disease:
Hemophilia B (F9 deficiency)
Hemophilia B is a deficiency of factor__:
9
Factor 9 can be activated by ___:
11a+Ca, or Russell Viper Venom
T/F
Hemophilia B is sex-linked and less common than Hemophilia A:
True
Which has a longer half-life, F8:C or F9 concentrates:
F9: 24 hrs
F8:C 12 hrs
Can Hemophilia B be acquired, and if so, how:
Yes.
Liver disease, Vit K deficiency, oral antiocoagulant therapy
List the respective deficiency of each Hemophilia:
A:
B:
C:
A: 8:C
B: 9
C: 11
Which coag test would be abnormal in Hemophilia B, and would mixing studies correct with NPP and AP:
APTT (F9 is intrinsic)
Yes
Aged serum contains which factors:
7 9 10 11 12
Adsorbed plasma has which factors removed:
Vit K dependent
Adsorbed plasma contains which factors:
1 5 8 11 12
Hemophilia C is also known as ____:
Rosenthal Syndrome
Rosenthal syndrome is also known as ______ and is predominantly in the ____ population:
Hemophilia C
Ashkenazi Jewish population (1:8)
Bleeding after dental surgery/extraction in an Ashkenazi Jew, think ____:
Hemophilia C
Why is F11 replacement not needed in Hemophilia C unless patient is scheduled for surgery:
F11 is early in the cascade, and there are other ways it can be initiated
__or ____ possible in severe F11 deficiency:
alloantibodies or inhibitors
F11 levels >120% increase risk of ___:
thrombosis
Overabundance of F11 will bind to ___ binding sites, preventing ____ from activating, therefore preventing fibrinolysis, resulting in ____:
plasminogen
plasminogen
thrombosis
Which coag test will be abnormal in Hemophilia C:
APTT
vWD occurs almost as frequently as ____:
Hemophilia A
Will the BT be increased or decreased in vWD:
increased
Plt aggregation in vWD is impaired with ___:
Ristocetin
Factor 7 deficiency (aka Proconvertin) has symptoms similar to factor ___ deficiency:
8
Deficiency of factor___ will have a prolonged PT that will fully correct with RVV and mixing with aged serum:
Factor 7 deficiency
How does RVV correct a Factor 7 deficiency:
It activates Factor 10
T/F
Factor 10 deficiency is extremely rare, can occur at any age, and can be due to quantitative or qualitative abnormalities of the Factor 10 molecule:
True.
Is Stypven Time prolonged in Factor 10 deficiency:
Yes. (depends on F2, 5, 10 w/ phospholipid)
With the Factor 10 assay, variant forms of F10 could show ____ between tests:
discrepancies
___activity of F10 is considered adequate for hemostasis:
10%
Factor 5 deficiency is also known as ___:
parahemophilia
Factor 5 is also called _____ because of rapid deterioration in plasma at room temp:
labile
F5 is a catalyst in conversion of ___to ___:
F2–>F2a
Acquired F5 deficiency can occur from specific Ab acquired after ____ or use of ___ in surgery:
childbirth
fibrin glue
1/2 of F5 deficient patients have an increased __ due to plt-related function of F5 of binding ___ to plt surface:
BT
F10
In testing for a F5 deficiency, specimens must be ____:
platelet poor (<10k)
Deficiency of this delays generation of thrombin, causing severe hemorrhagic symptoms:
Factor 2 (Prothrombin)
The ‘Prothrombin Complex’ includes everything from ___ to ___:
F2 to Thrombin
Hypoprothrombinemia is a deficiency of this factor:
F2 (prothrombin)
Dysprothrombinemia is a structural defect of ___ that causes _____:
F2 (prothrombin)
impaired activity
A single point mutation on chromosome 11 leads to a mutation of factor___ and is the 2nd most common cause of _____:
F2 (prothrombin)
inherited thrombophilia
Does the Prothrombin Mutation on Chromosome 11 lead to an increased risk of clotting or bleeding:
clot risk
- risk factor for MI/stroke in young pts
- mostly caucasian
____deficiency is not associated with clinical bleeding or hemorrhage, patients are asymptomatic and post no surgical risk, even though their APTT is prolonged:
F12 (Hageman factor)
Deficiencies of Fletcher or Fitzgerald factors will both show marked prolongation of ____:
APTT
In Fletcher deficiency, contact activation time with APTT kaolin-like reagents changes with incubation time intervals, the APTT intervals will progessively ___:
shorten
Is there any racial predilection or apparent clinical bleeding associated with Fletcher or Fitzgerald factor deficiencies:
No.
One could acquire inhibition of factor____ following TB treatment with Isoniazid:
F13
Autoimmune inhibitors of F8:C most commonly result from___ and produce ___class of antibodies:
F8:C transfusions
IgG
(can also be seen in patients with RA, SLE, drug rx, post partum, etc)
Poor diet, biliary obstruction, malabsorption, coumadin therapy, long term antibiotic tx can all result in this acquired coag disorder:
Vitamin K deficiency
affecting factors 2, 7, 9, 10, Proteins C,S
Heparin binds ___ which greatly enhances ability to bind and inactivate ___:
autoprothrombin 3
thrombin
TT is affected by ___ and ____:
FDP’s
heparin
If PT, APTT, and TT are all prolonged, presence of ___ should be considered before factor deficiencies:
heparin
How would you test for heparin in sample:
add protamine sulfate to inhibit heparin and normalize prolonged tests
Circulating anticoagulants are also called ____:
Inhibitors
List the two types of inhibitors:
1) Specific (Ab to specific factor)
2) Non-specific (LA- interferes with phospholipid component of reagent)
Inhibitors are also called:
Circulating anticoagulants
_____ should be suspected in anyone with no prior history who presents with massive bruising or hematoma:
Acquired hemophilila (F8:C inhibition via autoantibodies)
Autoantibodies to F8:C are most often seen in patients with ___ and has a mortality rate of ___:
RA
SLE
Drug rxns
*~20%
Allontibodies to F8:vWF complex are frequently encountered and due to ___:
Transfusion
____ should be suspected in any hemophiliac if transfused factor replacement products appear to have reduced effectiveness, hemostasis is hard to achieve, or both:
Inhibitors
Factor __ inhibitors are rare, classified as alloAb’s, and due to transfusions. Patients do not bleed often, just ___:
F9
differently (can see hemarthrosis, muscle and soft tissue hemorrhages)
In both F8:C and F10, inhibiting antibodies do/do not increase bleeding frequency:
Do not
What are the two goals of treating specific inhibitors:
1) stabilize hemostasis
2) rid body of antibody
In treating specific inhibitors, a ___titer can be treated with high concentrations of Factor concentrates to overwhelm binding sites, while a ___ titer can be treated with steroids, plasmapharesis, cytotoxic treatments, etc:
Low
High
_____ inhibitors are usually accidentally discovered with prolonged APTT screening test, and patient will have increased risk of ___:
Non-specific
clotting
With non-specific inhibitors, prolongation of tests will be see ____, while hypercoagulable state will be seen ____:
in vitro
in vivo
PT and APTT are ___ dependent tests:
phospholipid
T/F
IgG/IgM interefere with phospholipid dependent tests:
True
Would mixing studies correct a non-specific inhibitor with NPP:
No. It’s not a factor deficiency.
APLS stand for:
Antiphospholipid Antibody Syndromes
APLS are the most common causes of acquired coag defects associated with thrombosis, list the 4 covered in class:
- aPL (antiphospholipid Ab’s)
- aCL (anticardiolipin Ab’s)
- LAC/LA (Lupus Anticoagulant)
- CAPS (catastrophic antiphos syndrome)
____causes infarction/clots in multiple organs with a ~50% fatality rate:
CAPS
Catastrophic antiphospholipid syndrome
aCL stands for:
anti-cardiolipin
LA: autoantibodies react against phospholipid portion of ______:
APTT reagent
Is LA more frequently associated with venous or arterial thrombosis:
Venous
This develops in 31% of SLE patients, and in those taking psych meds, anti-emetics, antihistamines, and those with lymphoproliferative disorders:
LA
Patients with SLE and LA have a 30-40% risk of ____:
Thrombosis
more likely venous than arterial
Which coag test is abnormal with LA:
APTT (PT could also be affected)
LA autoantibodies react against the phospolipid portion of APTT reagent
Would a factor assay be abnormal with LA:
No. It is not a factor deficiency.
What test could be done to exclude another coagulopathy that could give similar lab results to that of LA:
Factor assays.
LA will be normal since it is not a factor deficiency.
List the order of factors from intrinsic pathway activation to the fibrin clot:
Fletcher (contact) Fitzgerald (contact) 12 11 9 8 10 5 2 1 13
List the order of factors from extrinsic pathway activation to the fibrin clot:
3 (trauma) 7 10 5 2 1 13
What converts fibrinogen to fibrin:
Thrombin
What converts plasminogen to plasmin:
t-PA
____ is triggered by the exposure of negative charge on collagen; Factors Fitzgerald, Fletcher, and 12 all for a complex on the collagen:
Intrinsic pathway
____ is the primary and most important pathway, and is triggered by the exposure of F3 in the damaged blood vessel wall to the circulating F7:
Extrinsic pathway
List the 3 components in the cascade that utilize negative feedback to enable clot dissolution:
Active Protein C
TFPI
Antithrombin
____ works on F10 and Thrombin, the effect is enhanced if heparin is present:
Antithrombin
TFPI inhibits conversion of ___ to ___:
7 to 7a
If antithrombin is inhibiting Thrombin, what conversion cannot take place:
Fibrinogen to Fibrin
Activated Protein C can inhibit the conversion of these two factors to their active forms:
Protein C can inhibit:
8 to 8a
5 to 5a
Antithrombin can inhibit the conversion of these two:
10 to 10a
Fibrinogen to fibrin (by blocking thrombin)
