Krafts- Thrombotic Disorders

Question 1

What are the three primary risk factors that can lead to thrombosis?

Answer 1

1. endothelial damage
2. stasis
3. hypercoagability

Question 2

What are the hereditary thrombotic disorders?

Answer 2

Factor  V leiden
ATIII def
Protein C def
Protein S def
factor I gene mutation
Homocysteinemia

Question 3

What are acquired thrombotic disorders?

Answer 3

Antiphospholipid Ab

Question 4

What is the most common cause of unexplained thrombosis?

Answer 4

Factor V leiden

Question 5

what causes factor V leiden?

Answer 5

Mutated factor V gene--> 
abnormal factor V-->
can't be cleaved by protein C> 
can't be turned off> 
keep making fibrin> clot

Question 6

Who usually gets factor V leiden?

Answer 6

%5 of caucasians have it

it’s VERY rare in non-caucasians

Question 7

How do you diagnose Factor V leiden?

Answer 7

PTT and INR are NOT helpful b/c factor V will look normal. The only problem is that it can’t be turned off.

Need genetic testing

Question 8

How do you treat factor V leiden?

Answer 8

Don’t treat unless a thrombus present

if thrombus present> give anticoagulant

Question 9

What is ATIII?

Answer 9

Natural anticoagulant
potentitated by heparin
Inhibits IIa, VIIa, IXa, Xa, XIa

Question 10

What happens if ATIII gene is mutated?

Answer 10

you produce LESS ATII, but it’s very rare

homozygotes- can’t survive
heterozygotes- half get clots

Question 11

What are protein C and S?

Answer 11

natural anticoagulants

C is also fibrolytic and antifinflammatory

Question 12

What does protein C do?

Answer 12

anticoagulant: inactivates Va and VIIIa
fibrinolytic: promotes t-PA action

anti-inflammatory: keeps cytokines low

Question 13

What happens if there’s a mutation in a protein C gene?

Answer 13

mutated gene produces less protein C

dx w/ functional testing

Question 14

Warfarin-induced skin necrosis is related to what deficiency?

Answer 14

protein c def

need to give heparin + warfarin b/c warfarin hypercoagulates first d/t inhibition of II, VII, IX, X, prot C and S

Question 15

When does purpura fulminans occur?

Answer 15

thrombotic state + vascular injury–> skin necrosis

Question 16

Purpura fulminans is associated w/ what?

Answer 16

coagulopathies

sepsis

Question 17

How do you treat purpura fulminans?

Answer 17

give protein C

Question 18

What is factor II?

Answer 18

prothrombin

Question 19

What happens in a factor II gene mutation?

Answer 19

mutated gene makes too much prothrombin
prothrombin itself is normal
rare in non-caucasians

–> increased clot risk

Question 20

What is hyperhomocysteinuria?

Answer 20

rare metabolic disorder
deficient trans sulphuration enzyme
increased homocysteine in blood and urine
increased risk of thrombosis and premature artherosclerosis

Question 21

What is homocysteine?

Answer 21

amino acid
made from mehtionine
matins mylein
converts dietary folate

Question 22

What is homocysteinuria?

Answer 22

rare metabolic disorder

Question 23

Too much homocysteine leads to….

Answer 23

thrombosis

Question 24

What causes homocysteinemia?

Answer 24

MTHFR gene mutation

homocysteinemia is d/t B12/folate def

Question 25

What problems are caused by increased homocysteine?

Answer 25

Toxic to endothelium>

forms ROS which interfere with NO

Question 26

What happens in heterozygous homocysteinemia?

Answer 26

increased thrombosis and premature athersclerosis
risk of venous thrombosis 2.5 x normal
risk of arterial thrombosis 10 x normal

Question 27

What should you know about Antiphospholipid Ab?

Answer 27

Autoantibodies against phospholipids
Falsely prolong INR
may cause thromboses
antiphospholipid syndrome is serious

Question 28

How does antiphospholipid Ab affect children, adults and the elderly?

Answer 28

children: infection mild risk
adults: autoimmune diseases, mod risk
elderly: drugs, no risk

Question 29

What are the functions of antiphospholipid Abs?

Answer 29

bind to phospholipids
screw up coagulation tests (bind up PTT/PT reagent> specimen doesn’t clot> test result appears prolonged)

also screw up DAT test and syphilis test

Question 30

What happens in antiphospholipid antibody syndrome?

Answer 30

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

Question 31

How do you detect Abs in antiphospholipid antibody syndrome?

Answer 31

1. order a PTT
2. if prolonged, order a PTT mixing study to see if PTT corrects or not
3. If normal, antibody may still be present–> order fancy tests.