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54 Cards in this Set
- Front
- Back
What is vWF and it's 2 functions?
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the glue that mediates platelet adhesion to the sub-endothelium
(radiator leak plug) "Taxi" for VIII VIII is very unstable otherwise. |
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When 2ndary hemostasis fails, we plug the holes ok, but we're not making the ....
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...permanent repair.
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Most common inherited bleeding disorder? Can it have different degrees?
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vWD. 1% prevalence.
Yes. |
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Are Hemophilia A and B distinguishable on clinical grounds?
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Not really.
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What are a group of inherited or acquired hematologica conditions that predispose to thrombosis? How do they usually manifest?
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Thrombophilias
Venous thromboembolism |
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Match: Red/White with Arterial/Venous Thrombosis
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Red = venous
white = arterial |
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Are thrombophilias as relevant in arterial thrombosis as they are in arterial thrombosis?
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no.
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What is and what are the characteristics of the Prothrombin 20210 mutation?
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point mutation in factor II (prothrombin) gene
Encodes for *slightly* elevated FII lvls. Thrombosis due to "gain of function" in co-ag sys. |
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What are some inherited deficiencies that can result in thrombophilia? inherited resistances?
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Deficiency of protein C, protein S, or antithrombin III
resistance to activated protein C |
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What is the most prevalent known inherited form of thrombophilia? What are >90% of the incidence of this phenotype due to genotypically?
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resistance to activated Protein C
Factor V leiden genotype. |
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Which racial group is at greater risk for VT? What are their mutations that predispose them to it?
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AA.
Largely uncharacterized. |
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What does Factor V Lieden actually do?
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slows down the cleavage of Factor Va... it stays active longer.
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What is Antiphospholipid Antibody Syndrome?
What are two indicated antibodies that might be responsible? |
Primary or secondary syndrome consisting of Thrombosis or recurrant miscarriage
AND persistent antiphospholipid antibody Lupus Inhibitor Anticardiolipin Ab |
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What are some environmental risk factors for VTE?
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Estrogens, Surgery, trauma, immobilization, airline travel, catherters, cancer
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Do progestin-only pills raise VTE risk as much as the estrogen combo pills?
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no.
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Your risk of thrombosis goes ___ with age.
* recall the graphs he showed with the dotted-line threshold |
up.
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When should we screen for Thrombophilia?
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Neonatal purpura fulminans
Unprovoked VTE VTE under 30 Recurrent VTE VTE + pos. fam. history VTE @ unusual sites VTE secondary to preg., oral con., HRT |
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Although DIC may result in bleeding, when you look at autopsy/histology, you always see...
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... thrombosis.
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Common etiologies of DIC: (big 3)
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infection/sepsis
cancer obstetric emergencies trauma |
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DIC laboratory findings?
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Reduced fibrinogen
Elevated fibrin split products Reduced platelets Micro-angiopathic hemolysis (red cell fragmentation)…but only in ≈30% cases Prolonged PT (and PTT, TT) Consumption of natural anticoagulants (such as antithrombin) |
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What is a syndrome of DIC with skin necrosis and secondary hemorrhage? Indicative of?
Etiologies? |
Purpura Fulminans
High grade DIC. certain forms of sepsis (meningococcus, pneumoncoccus) homozygous deficiency of protein C or Protein S. |
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Do both LMW and HMW heparin have pentasaccharide complexes?
How do they differ? |
Yes.
HMW can accelerate the inactivation of IIa by ATIII w/o a ternary complex. LMW accelerates inactivation of Xa by ATIII. |
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What are the clinical applications of LMWH?
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prevention of DVT/PE in patients undergoing lower body surgery.
Treatment of DVT/PE |
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What is still the only anti-coag approved by the FDA?
How does it work? |
Warfarin.
Antagonizes Vitamin K indirectly by preventing it's recycling --> synthesis of dysfunctional co-ag factors. |
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How much of the US population is taking warfarin?
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1%
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When should indefinite anticoag therapy be considered?
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Recurrent event
Life-threatening events cerebral or visceral vein thrombosis V Leiden or prothrombin 20210 homozygote. Combined Thrombophilia Persistent antiphospholipid antibodies. |
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How do we treat asymptomatic carriers of some Thrombophilia disorder?
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prophylaxis at times of increased risk.
Avoid oral contraceptives... or at least educate them well on the risks. |
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How do we treat those who have had their first thrombotic event? In general, is life-long anticoag indicated? What if the event was associated with a recognizable acquired trigger?
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Standard therapy with iv heparin or low MW heparin, followed by warfarin to maintain INR of 2 - 3 for approximately 6 months
In general, life-long anticoagulation is not indicated, especially if the event was associated with recognizable acquired trigger(s) Even moreso no, then. |
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Are vWF and f.VIII covalently associated in plasma?
Without vWF, what is the half-life of VIII? With it? |
No, they're bound non-covalently.
1-2hrs 8-12hrs. |
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What on platelets interacts with immobilized vWF factor?
What other connections are required for optimal platelet adhesion to the site of injury? |
glycoprotein Ib
activated integrin a2B1 |
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What is major site of synthesis of f.VIII?
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Likely to be in the liver
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What are Weibel-Palade bodies?
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granules of vWF stored in endothelial cells
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Where is vWF stored?
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In granules in endothelial cells
in granules in platelets (a-granules) |
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Which gene is fVIII encoded on?
vWF? |
X-chromosome
chromosome 12 |
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Which type of bleeding disorder is generally more common with 'muco-cutaneous' bleeding: menorrhagia, epistaxis, easy bruising?
'Deep tissue bleeding': hemathrosis, soft tissue and intra-muscular bleeding? Petechiae? |
vWD and other primary hemostatis disorders
Factor deficiency or anticoag medication toxicity thrombocytopenias - but can be seen in really bad vWD too. |
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Desmopressin Acetate is also known as...
When can it be used in bleeding disorders? Why does it work? When will it not work? |
....DDAVP.
mild hemophilia A and vWD. causes release of pre-formed stores of vWF and fVIII. when stores of fVIII are <5%. |
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Differentiate b/t Hemophilia A and vWD using lab values (cite all good Dx lab values for both, compare/contrast).
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Hemophilia A
- PT normal - PTT prolonged - PFA-100 normal - 1:1 corrects - vWF lvls normal - fVIII lvls low vWD: - PT normal - PTT prolonged - PFA-100 abnormal - fVIII low - vWF low - 1:1 mix fixes PTT |
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What are the tests of secondary hemostasis? Primary?
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TT, PT, PTT
PFA-100, bleeding time (prick) |
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Three sides of Virchow's Triad?
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vessel wall changes
flow changes blood constituent changes |
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Does the Prothromvin G20210A mutation lead to a sig. increased risk of arterial thrombosis (stroke, MI)?
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No.
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APC is...
What does it do? What is it's required cofactor? |
Activated Protein C.
Inactivates Va and VIIIa Protein S |
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Protein C and Protein S are _____ dependent factors.
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Vit. K
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AT is....
What does it do? What does it do + heparin? |
...antithrombin
Inactivates Xa and IIa slowly works a LOT faster. |
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What do heterozygous def. of C, S, or AT cause? Homozygous?
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increased risk of VT, but not arterial thrombosis.
severe prenatal complications/death. |
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If exogenous APC is added to patient plasma in the laboratory, and it doesn't prolong PTT as much as expected (or at all), what might you suspect?
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Factor V Leiden.
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Dysfibrinogenemia describes a condition in which...
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.... fibrin generated from abnormal fibrinogen is resistant to breakdown by the fibrinolytic system.
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You gave your patient herparin... and clotting time went up! Oh shit! What's wrong?
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Heparin-induced thrombocytopenia.
Stop the freaken' heparin. |
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What is a complex pathological syndrome caused by chaotic intravascular thrombin generation?
Does it lead to clotting or bleeding? Why? Which labs are most useful in Dx? |
DIC
Can be either/or/both depending on the etiology. We have hyperfinbrinolysis going on along with the rapid and uncompensated consumption of clotting factors. PT, platelet count, AT lvls PT will be prolonged Platelets will be low AT will be low fibrin degradation products will be elevated fibrinogen lvls will be low. |
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What is the shortest-lived clotting factor under normal physiological conditions?
What implications does this have in warfarin/cumadin therapy? |
VII
PT/INR may become prolonged as soon as all the good VII is cleared... the patient may thus appear to be anti-coag when they're NOT. |
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In the context of warfarin therapy, when is it believed that protection from thrombosis is complete?
Why must we continue heparin bridging 24hrs after INR reaches the target? Is there any value to high-loading initial doses of warfarin? |
When funcitonal II lvls are reducted to their target range.
B/c the INR will be affected by the must faster decrease in functional lvls of VII... but the patient is still not anticoagulated. No. |
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Which of the following disorders is most appropriately treated with DDAVP?:
a. Severe hemophilia A b. Type 3 VWD c. Mild hemophilia A d. Mild hemophilia B e. Mild hemophilia A or hemophilia B |
c
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Which of the following statements is correct
a. Von Willebrand factor circulates bound to factor V b. Antithrombin inactivates factor Va c. Factor Va is cofactor for factor IXa d. Activated protein C inactivates factor Va e. Factor V levels are reduced in patients treated with warfarin |
D
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Which of the following laboratory studies is not compatible with a diagnosis of severe inherited hemophilia A?:
a. Prolonged prothrombin time b. Prolonged PTT c. Correction of prolonged PTT on mixing with normal plasma d. Normal thrombin clotting time (TCT) e. Normal PFA-100 closure times |
A
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You obtain a coagulation screen on a patient with a recent deep vein thrombosis, now on day 5 of unfractionated heparin and warfarin combined therapy. Which of the following laboratory tests would be surprising?:
a. INR = 2.5 b. PTT = 65 seconds c. TCT > 60 seconds d. Anti-Xa activity = 0 e. PFA-100 closure times normal |
D, I think.
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