Ho: Hemophilia And Thrombophilia

Front 1

What is vWF and it's 2 functions?

Back 1

the glue that mediates platelet adhesion to the sub-endothelium
(radiator leak plug)

"Taxi" for VIII
VIII is very unstable otherwise.

Front 2

When 2ndary hemostasis fails, we plug the holes ok, but we're not making the ....

Back 2

...permanent repair.

Front 3

Most common inherited bleeding disorder? Can it have different degrees?

Back 3

vWD. 1% prevalence.

Yes.

Front 4

Are Hemophilia A and B distinguishable on clinical grounds?

Back 4

Not really.

Front 5

What are a group of inherited or acquired hematologica conditions that predispose to thrombosis? How do they usually manifest?

Back 5

Thrombophilias

Venous thromboembolism

Front 6

Match: Red/White with Arterial/Venous Thrombosis

Back 6

Red = venous
white = arterial

Front 7

Are thrombophilias as relevant in arterial thrombosis as they are in arterial thrombosis?

Back 7

no.

Front 8

What is and what are the characteristics of the Prothrombin 20210 mutation?

Back 8

point mutation in factor II (prothrombin) gene

Encodes for *slightly* elevated FII lvls.

Thrombosis due to "gain of function" in co-ag sys.

Front 9

What are some inherited deficiencies that can result in thrombophilia? inherited resistances?

Back 9

Deficiency of protein C, protein S, or antithrombin III

resistance to activated protein C

Front 10

What is the most prevalent known inherited form of thrombophilia? What are >90% of the incidence of this phenotype due to genotypically?

Back 10

resistance to activated Protein C

Factor V leiden genotype.

Front 11

Which racial group is at greater risk for VT? What are their mutations that predispose them to it?

Back 11

AA.

Largely uncharacterized.

Front 12

What does Factor V Lieden actually do?

Back 12

slows down the cleavage of Factor Va... it stays active longer.

Front 13

What is Antiphospholipid Antibody Syndrome?

What are two indicated antibodies that might be responsible?

Back 13

Primary or secondary syndrome consisting of Thrombosis or recurrant miscarriage
AND
persistent antiphospholipid antibody

Lupus Inhibitor
Anticardiolipin Ab

Front 14

What are some environmental risk factors for VTE?

Back 14

Estrogens, Surgery, trauma, immobilization, airline travel, catherters, cancer

Front 15

Do progestin-only pills raise VTE risk as much as the estrogen combo pills?

Back 15

no.

Front 16

Your risk of thrombosis goes ___ with age.

* recall the graphs he showed with the dotted-line threshold

Back 16

up.

Front 17

When should we screen for Thrombophilia?

Back 17

Neonatal purpura fulminans

Unprovoked VTE
VTE under 30
Recurrent VTE
VTE + pos. fam. history
VTE @ unusual sites
VTE secondary to preg., oral con., HRT

Front 18

Although DIC may result in bleeding, when you look at autopsy/histology, you always see...

Back 18

... thrombosis.

Front 19

Common etiologies of DIC: (big 3)

Back 19

infection/sepsis
cancer
obstetric emergencies

trauma

Front 20

DIC laboratory findings?

Back 20

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)

Front 21

What is a syndrome of DIC with skin necrosis and secondary hemorrhage? Indicative of?

Etiologies?

Back 21

Purpura Fulminans

High grade DIC.

certain forms of sepsis (meningococcus, pneumoncoccus)

homozygous deficiency of protein C or Protein S.

Front 22

Do both LMW and HMW heparin have pentasaccharide complexes?

How do they differ?

Back 22

Yes.

HMW can accelerate the inactivation of IIa by ATIII w/o a ternary complex.

LMW accelerates inactivation of Xa by ATIII.

Front 23

What are the clinical applications of LMWH?

Back 23

prevention of DVT/PE in patients undergoing lower body surgery.

Treatment of DVT/PE

Front 24

What is still the only anti-coag approved by the FDA?

How does it work?

Back 24

Warfarin.

Antagonizes Vitamin K indirectly by preventing it's recycling --> synthesis of dysfunctional co-ag factors.

Front 25

How much of the US population is taking warfarin?

Back 25

1%

Front 26

When should indefinite anticoag therapy be considered?

Back 26

Recurrent event
Life-threatening events
cerebral or visceral vein thrombosis
V Leiden or prothrombin 20210 homozygote.
Combined Thrombophilia
Persistent antiphospholipid antibodies.

Front 27

How do we treat asymptomatic carriers of some Thrombophilia disorder?

Back 27

prophylaxis at times of increased risk.

Avoid oral contraceptives... or at least educate them well on the risks.

Front 28

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?

Back 28

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.

Front 29

Are vWF and f.VIII covalently associated in plasma?

Without vWF, what is the half-life of VIII? With it?

Back 29

No, they're bound non-covalently.

1-2hrs

8-12hrs.

Front 30

What on platelets interacts with immobilized vWF factor?

What other connections are required for optimal platelet adhesion to the site of injury?

Back 30

glycoprotein Ib

activated integrin a2B1

Front 31

What is major site of synthesis of f.VIII?

Back 31

Likely to be in the liver

Front 32

What are Weibel-Palade bodies?

Back 32

granules of vWF stored in endothelial cells

Front 33

Where is vWF stored?

Back 33

In granules in endothelial cells

in granules in platelets (a-granules)

Front 34

Which gene is fVIII encoded on?

vWF?

Back 34

X-chromosome

chromosome 12

Front 35

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?

Back 35

vWD and other primary hemostatis disorders

Factor deficiency or anticoag medication toxicity

thrombocytopenias - but can be seen in really bad vWD too.

Front 36

Desmopressin Acetate is also known as...

When can it be used in bleeding disorders?
Why does it work?
When will it not work?

Back 36

....DDAVP.

mild hemophilia A and vWD.

causes release of pre-formed stores of vWF and fVIII.

when stores of fVIII are <5%.

Front 37

Differentiate b/t Hemophilia A and vWD using lab values (cite all good Dx lab values for both, compare/contrast).

Back 37

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

Front 38

What are the tests of secondary hemostasis? Primary?

Back 38

TT, PT, PTT

PFA-100, bleeding time (prick)

Front 39

Three sides of Virchow's Triad?

Back 39

vessel wall changes

flow changes

blood constituent changes

Front 40

Does the Prothromvin G20210A mutation lead to a sig. increased risk of arterial thrombosis (stroke, MI)?

Back 40

No.

Front 41

APC is...

What does it do?

What is it's required cofactor?

Back 41

Activated Protein C.

Inactivates Va and VIIIa

Protein S

Front 42

Protein C and Protein S are _____ dependent factors.

Back 42

Vit. K

Front 43

AT is....

What does it do?

What does it do + heparin?

Back 43

...antithrombin

Inactivates Xa and IIa slowly

works a LOT faster.

Front 44

What do heterozygous def. of C, S, or AT cause? Homozygous?

Back 44

increased risk of VT, but not arterial thrombosis.

severe prenatal complications/death.

Front 45

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?

Back 45

Factor V Leiden.

Front 46

Dysfibrinogenemia describes a condition in which...

Back 46

.... fibrin generated from abnormal fibrinogen is resistant to breakdown by the fibrinolytic system.

Front 47

You gave your patient herparin... and clotting time went up! Oh shit! What's wrong?

Back 47

Heparin-induced thrombocytopenia.

Stop the freaken' heparin.

Front 48

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?

Back 48

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.

Front 49

What is the shortest-lived clotting factor under normal physiological conditions?

What implications does this have in warfarin/cumadin therapy?

Back 49

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.

Front 50

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?

Back 50

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.

Front 51

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

Back 51

c

Front 52

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

Back 52

D

Front 53

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

Back 53

A

Front 54

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

Back 54

D, I think.