Antihemostasis

Question 1

what is hemostasis?

Answer 1

the stopping of a flow of blood

it’s a balance between making clots and controlling clot formation

happens when a blood vessel is damaged

Question 2

what is antihemostasis?

Answer 2

the process of keeping clotting in check

Question 3

what are the two main mechanisms of antihemostasis?

Answer 3

1. stopping the coagulation cascade

2. breaking down clots= fibrinolysis

Question 4

what are 3 inhibitors of the coagulation cascade?

Answer 4

1. antithrombin
2. protein C
3. protein S

Question 5

what does the coagulation cascade do?

Answer 5

makes fibrin for the platelet plug

Question 6

what does antithrombin do?

Answer 6

1. inhibits the activated forms of all the serine proteases = IIa, VIIa, IXa, Xa, XIa, and XIIa
2. forms irreversible bonds with activated coagulation factors which stops the action of the coagulation factors and clears them from the circulation

Question 7

what increases the effect of antithrombin?

Answer 7

heparin

in the presence of heparin, antithrombin is much, much more effective

Question 8

what does antithrombin have the strongest effect on?

Answer 8

thrombin aka serine protease IIa

factor Xa

Question 9

what serine protease is thrombin?

Answer 9

IIa

Question 10

what do proteins C and S do?

Answer 10

they act together to inhibits VIIIa and Va

both proteins must be present and working properly for the inhibition of both of these cofactors

Question 11

which serine protease is fibrin?

Answer 11

Ia

Question 12

what serine protease is fibrinogen?

Answer 12

I

Question 13

what part of the coagulation cascade is factor VIIIa?

Answer 13

intrinsic pathway

Question 14

what part of the coagulation cascade is factor Va?

Answer 14

final common pathway

Question 15

what is fibrinolysis?

Answer 15

breaking down clots

involves chopping up the fibrin that’s holding the clot together into little fragments

without fibrin holding the clot together, it simply dissolves

Question 16

when does fibrinolysis happen?

Answer 16

1. new clot formation!

2. breakdown clots that have formed abnormally to prevent irreversible damage downstream

Question 17

how is fibrinolysis used during new clot formation?

Answer 17

anti-intuitive but it’s because it’s critical to limit the size and scope of a clot

as soon as a clot is formed, fibrinolytic mechanisms kick in and “remodel” the clot to keep it to an appropriate size

Question 18

what enzyme breaks down fibrin?

Answer 18

plasmin

Question 19

what does fibrin do?

Answer 19

holds a clot together

Question 20

how is plasmin formed?

Answer 20

plasmin is formed from an inactive precursor molecule called plasminogen

tissue plasminogen activator, or tPA, catalyzes the conversion of plasminogen to plasmin

Question 21

how can you upregulate the formation of plasmin?

Answer 21

administering recombinant tissue plasminogen activator (tPA) in an effort to enhance breakdown of the pathologic thrombus

you should do this during early stages of an ischemic stroke

Question 22

what are the breakdown products of fibrin?

Answer 22

1. fibrin degradation products (FDPs)

2. D-dimers

Question 23

what are fibrin degradation products?

Answer 23

small fragments of fibrin that increase in the blood if we’re breaking down a clot

Question 24

why is measuring FDPs a problem?

Answer 24

1. the test is SUPER sensitive

it will pick up FDPs that are formed by breaking down even tiny, minor, non- pathologic clots

2. we can get FDPs from breaking down fibrinogen, too (not just fibrin)

**so the presence of FDPs doesn’t always mean that fibrin (in a clot) is being broken down

Question 25

fibrin vs. fibrinogen

Answer 25

fibrin is made from fibrinogen!

a soluble protein present in blood plasma, from which fibrin is produced by the action of the enzyme thrombin

Question 26

how is fibrin made?

Answer 26

the enzyme thrombin converts fibrinogen into fibrin

Question 27

what are D-dimers?

Answer 27

fibrin gets turns into cross-linked fibrin via factor XIII enzyme

cross-linked fibrin is then broken down by plasmin into D-dimers

so when you see D-dimers in the blood you know they’re actually from a real clot and not fibrinogen since fibrinogen doesn’t get crosslinked by factor XIII

Question 28

what’s the problem with trying to measure D-dimer to figure out fibrin levels?

Answer 28

same thing that was wrong with the FDP assay!

D-dimers become visible in blood with even minor clotting - like the kind that happens if you sit on your behind all day in class and damage tiny capillaries

it is actually WAY too sensitive to use as proof that a patient has a pathologic thrombus

Question 29

what’s the positive side of FDP assay or D-dimer test?

Answer 29

since they’re both ultra sensitive, if you do the test and it comes back negative
then we can be sure that the patient does not have a pathologic thrombus

Question 30

What is the best clinical application of the D-dimer test?

Answer 30

due to the high sensitivity of the D-dimer test, the best clinical application is for the ruling OUT of pathologic thrombi

if the D-dimer test is normal, you can be very sure that the patient does not have a pathologic thrombus

FDP and D-dimer assays are not great for ruling IN a clot, but they are great for ruling OUT a clot

Question 31

What is the essential component of a thrombus that, when cleaved, causes dissolution of clots and production of FDPs?

Answer 31

fibrin

a platelet plug, by itself, is not stable. It will quickly dissolve if it is not stabilized by fibrin

Question 32

The process of fibrinolysis is an enzymatic reaction that results in degradation of fibrin. The process is carried out by which enzyme?

Answer 32

plasmin