Krafts - Thrombolytic Disorders

Front 1

The incidence of thrombosis (both arterial and venous) increases with age and is usually associated with the presence of risk factors: atherosclerosis, trauma, osbesity, prolonged _________, varicose veins, pregnancy, _____ ________ use, MI, a-fib, adenocarcinoma, smoking, cardiomyopathy

Back 1

immobilization
oral contraceptive

Front 2

There are 3 main thrombogenic mechanisms:
________ damage
abnormal _____ flow
hyper________

Back 2

endothelial
blood
hypercoagulability

Front 3

Thrombosis often caused by too many risk factors, but suspect disorder if:
other family members have ____ thrombosis, if it's in a weird place (not ___, lungs), recurrent thromboses, young (<__), your pt has had ______

Back 3

venous
leg
50
miscarriages

Front 4

Hereditary Thrombotic Disorders:
factor _ Leiden
ATIII deficiency
protein _ and _ deficiency
factor II (______) gene mutation
hyperhomocysteinemia

Back 4

V
C and S
prothrombin

Front 5

Acquired thrombotic disorders:
___________ antibodies

Back 5

Antiphospholipid

Front 6

Which is the most common hereditary thrombotic disorder? About half of the patients with unexplained thrombosis have it. About 5% of caucasians carry mutation.

Back 6

Factor V Leiden

Front 7

Factor V Leiden is a factor V with a single ____ ______ (glutamine instead of arginine). Very close to factor V, still participates in coagulation cascade BUT different enough that ______ _ cannot cleave it!

Back 7

point mutation
protein C

Front 8

Do heterozygotes have a risk of a bad clot with the factor V Leiden mutation?

Back 8

Yes, they are 7x more likely to get a bad clot. Less severe than Homozygous - 80x more likely

Front 9

How do you test for factor V Leiden?

Back 9

PCR - DNA testing
NOT PTT or INR (proceeds down cascade fine, just not inhibited by Protein C)

Front 10

How do you treat factor V Leiden?

Back 10

DON'T! unless there is a thrombosis. If there is, give coumadin for awhile. If multiple episodes or other risk factors give long term anti-coag

Front 11

Antithrombin III is a natural coagulant that inhibits the _____ _______ (IIa, VIIa, IXa, Xa, XIa, XIIa). Heparin potentiates the action (uses ATIII)

Back 11

serine proteases

Front 12

Antithrombin caused by _____ mutations. About 0.05% of general population has ATIII deficiency. If you have it, about __% will develop a thrombus. Homozygosity is incompatible with life

Back 12

multiple
50%

Front 13

Things that keep clotting under control:
T___
A___
protein C and S
t__
plasmin

Back 13

TFPI
ATIII
tPA

Front 14

Can't treat ATIII deficient patients with Heparin why?

Back 14

Heparin works by potentiating ATIII and these patients don't have very much of it

Front 15

Diagnose ATIII/Protein C/S defiency by ______ ____ which tells you if the patient's antithrombin III/Protein C/S is working and if there's enough around

Back 15

functional testing

Front 16

Protein C is a natural anticoagulant that inactivates factors _ and ___ thereby shutting down clotting. It works with protein _ to do this

Back 16

V
VIII
S

Front 17

Many different mutations for protein C deficiency, 0.2% is _______ for the protein C mutation which makes them 7x more at risk for thrombosis.

Back 17

heterozygous (no homozygous humans have been reported)

Front 18

In addition to a risk of thrombosis, protein C deficient patients have a risk of ____ manifestations: warfarin-induced skin necrosis and ______ fulminans

Back 18

skin
purpura

Front 19

Protein S deficiency is essentially the same as Protein C deficiency (it's a cofactor). Differences: even more rare, _________ infants at risk for purpura fulminans

Back 19

homozygous

Front 20

Factor II (prothrombin) gene mutation - makes __ _____ prothrombin, but it's normal.
5% of ______ (rare in others)
Clot risk 2-20x normal

Back 20

too much
caucasians

Front 21

How do you test for a factor II deficiency?

Back 21

PCR

Front 22

Homocysteine is made from dietary _______, B12, folate. It’s important in maintaining ______, and it is essential for the conversion of dietary folate into the form of folate that participates in DNA _______. Homocysteinuria results from an increase of it in blood and urine

Back 22

methionine
myelin
synthesis

Front 23

Ways to get hyperhomocysteinemia:
Classic homocysteinURIA is rare autosomal _______ disorder from deficiency in trans-sulfuration enzyme
Elevated levels of homocysteine by ______ gene
Elevated levels of homocysteine from deficiencies of _____, B12, B4

Back 23

recessive
MTHFR (mutated methyl tetrahydrofolate reductase)
folate

Front 24

Hyperhomocysteinemia increases the risk of ________ and thrombosis because too much homocysteine can have bad effects on hemostasis (it causes ______ _____ expression) and vessel walls (it causes intimal _______). Also forms ROS and interferes with __ causing which normally causes vasodilation and is antithrombotic

Back 24

atherosclerosis
tissue factor
thickening
Nitric Oxide (NO)

Front 25

To diagnose hyperhomocysteinemia you can measure plasma level of homocysteine (homozygotes have very ___ levels), PCR test for _____ gene mutation, B12 and folate level deficiency test

Back 25

high
MTHFR

Front 26

In _________ antibody syndrome the patient has autoantibodies in plasma. Different types: anticardiolipin antibodies, anti-B2-glycoprotein antibodies, ____ anticoagulants

Back 26

antiphospholipid
lupus

Front 27

Autoantibodies in Antiphospholipid antibody syndrome happen to bind phospholipid part of ___ reagent so the specimen doesn't clot (FALSELY prolonged). Called "inhibitors" because they appear to inhibit _____ in test tube, but cause _______ in vivo

Back 27

PTT/PT (also screws up direct antiglobulin test and syphilis test)
coagulation
thrombosis

Front 28

Who develops antiphospholipid antibodies?
Children - after ______, mild risk of thrombosis
Adults - usually people with _____ diseases, moderate risk
Elderly - with ____, no risk

Back 28

infection
autoimmune
drugs

Front 29

Antiphospholipid antibody syndrome when patient with an antiphospholipid antibody has _____ or recurrent ______

Back 29

thrombosis
miscarriage

Front 30

To diagnose antiphospholipid antibody you can give ___, if prolonged it shouldn't correct with a ___ ______ study. Even if it's normal, pt may have the condition.

Back 30

PTT
PTT mixing study

Front 31

3 big mechanisms that predispose people to clotting “Virchow’s triad”
________ damage
Stasis
______________ – something wrong with the fibrin system

Back 31

endothelial
Hypercoagulablilty

Front 32

Purpura Fulminans:
Thrombotic state + vascular injury
Net result: skin ______
Associated with:
coagulopathies
sepsis (HUGE mortality rate)
Give ______ _

Back 32

necrosis
protein C