Thrombotic Disorders

Question 1

What are the three thrombotic risk factors in Vrichow’s triad?

Answer 1

endothelial damage
stasis
hypercoagulability

Question 2

What are some risks for endothelial damage?

Answer 2

atherosclerosis: hypertension, hyperlipidemia, obesity, smoking

Question 3

What aRe some risks for stasis?

Answer 3

immobilization
varicose veins
cardiac dysfunciton

Question 4

What are some risks for hypercoagulability?

Answer 4

trauma/surgery
carcinoma
estrogen/postpartum
thrombotic disorders

Question 5

If a patient has a thrombus, what are some clinidal findings that would make you consider a hereditary thrombotic disorder?

Answer 5

no obvious cause
family history
weird location (so not leg)
recurrent
patient is young
miscarriages

Question 6

WHat are the 6 hereditary thrombotic disorders we discussed?

Answer 6

factor V leiden
ATIII deficiency
Protein C def
Protein S def
Factor II gene mutaiton
Homocyteinemia

Question 7

WHat’s the one acquired thrombotic disorder we talked about?

Answer 7

antiphospholipid antibodies

Question 8

What’s the most common cuase of UNEXPLAINED thromboses?

Answer 8

factor V leiden

Question 9

What causes factor V leiden?

Answer 9

It’s a single point mutation in the factor V gene which makes it resistant to cleavage by protein C

In other words, it functions perfectly, but it can’t be turned off so you just get a constant produciton of thrombin

Question 10

What ethnic group is at highest risk for factor V leiden?

Answer 10

almost only in caucasians - 5% of us have it

Question 11

Why aren’t PTT and INR helpful in factor V leiden? How do you test for it then?

Answer 11

Because the factor V works just fine! It’s that it can’t be turned off. So those tests would be normal.

You gotta look for the mutation

Question 12

WHen do you treat factor V leiden? How do you treat it?

Answer 12

you don’t until there’s a thrombus - you use an anticoagulant for a while

if they have multiple episodes or other risk factors, you do long-term anticoagulation

Question 13

If you take a patient with Protein C deficiency and give them coumadin without bridging with heparin, what’s the super serius thing that can happen?

Answer 13

warfarin-induced skin necrosis

Question 14

Why does warfarin induced skin necrosis occur in protein C deficiency>

Answer 14

because warfarin will not only block the vit K-dependent factors, but protein C and S as well
C and S will actually be blocked well before the others do, so for the first few days you’re making them MORE likely to clot becaus eyoure taking way that natural anticoagulant
In Protein C deficiency, they’ll lose funciton in whatever little protein C they ave, they’ll get a clot in the periphery and the skin becomes necrotic because htey have no way of breaking it down

Question 15

If a patient is alreay in a thrombotic state and then they get a vascular injury, what can happen?

Answer 15

purpura fulminans - you get a clot in the skin and the skin turns necrotic

Question 16

What two things is purpura fulminans particularly associated with?

Answer 16

coagulopathies and sepsis

Question 17

What’s the treatment for purpura fulminans?

Answer 17

protein C, but it doens’t really work - there’s a huge mortality with this

Question 18

What’s worng with the factor II gene in the prothrombin mutation?

Answer 18

the mutation just means there’s way too much prothrombin - the prothrombin is normal in itself, but oto much

Question 19

Why do people with elevated homocysteine have higher risk for clots?

Answer 19

it’s toxic to endothelium because if forms ROS and it interfered with nitric oxide (a vasodilator and antithrombotic)

Question 20

What are hte antibodies that attack the phosphlipids?

Answer 20

IgG

Three variants: anticardiolipin, lupus anticoagulants and antibodies against other molecules

Question 21

What do the antibodies do

Answer 21

they bind to ANY phosphplipid

Question 22

So how do the antibodies screw up coagulation tests?

Answer 22

they bind up the PTT and PT reagents so the specimens can’t clot - the test will be falsely prolonged

Question 23

The antibodies inhibit coagulation in vitro, but what do they do in vivo?

Answer 23

They PROMOTE coagulation in vivo

Question 24

What’s the dangerous syndrome that can occur with thes antiphospholipid antibodies?

Answer 24

antiphospholipid antibody syndrome (duh)

recurrent thrombosis, recurrent spontaneous abortions, increased risk of stroke, pulmonary hypertension, renal failure

Question 25

How can you detect the antibodies?

Answer 25

1 order a PTT

2. if prolonged, order a PTT mixing study
3. If it doens’t correct, then the test is positive

BUT if it’s normal, antibodies may still be present, so consult if you really think you’re right

Question 26

In chidlren, what’s the usual thing associated with the antiphospholipid antibodies?
In adults? In elderly?

Answer 26

children - infection
adults - autoimmune diseases
elderly - drugs