Krafts- Thrombotic Disorders Flashcards
What are the three primary risk factors that can lead to thrombosis?
- endothelial damage
- stasis
- hypercoagability
What are the hereditary thrombotic disorders?
Factor V leiden ATIII def Protein C def Protein S def factor I gene mutation Homocysteinemia
What are acquired thrombotic disorders?
Antiphospholipid Ab
What is the most common cause of unexplained thrombosis?
Factor V leiden
what causes factor V leiden?
Mutated factor V gene--> abnormal factor V--> can't be cleaved by protein C> can't be turned off> keep making fibrin> clot
Who usually gets factor V leiden?
%5 of caucasians have it
it’s VERY rare in non-caucasians
How do you diagnose Factor V leiden?
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
How do you treat factor V leiden?
Don’t treat unless a thrombus present
if thrombus present> give anticoagulant
What is ATIII?
Natural anticoagulant
potentitated by heparin
Inhibits IIa, VIIa, IXa, Xa, XIa
What happens if ATIII gene is mutated?
you produce LESS ATII, but it’s very rare
homozygotes- can’t survive
heterozygotes- half get clots
What are protein C and S?
natural anticoagulants
C is also fibrolytic and antifinflammatory
What does protein C do?
anticoagulant: inactivates Va and VIIIa
fibrinolytic: promotes t-PA action
anti-inflammatory: keeps cytokines low
What happens if there’s a mutation in a protein C gene?
mutated gene produces less protein C
dx w/ functional testing
Warfarin-induced skin necrosis is related to what deficiency?
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
When does purpura fulminans occur?
thrombotic state + vascular injury–> skin necrosis
Purpura fulminans is associated w/ what?
coagulopathies
sepsis
How do you treat purpura fulminans?
give protein C
What is factor II?
prothrombin
What happens in a factor II gene mutation?
mutated gene makes too much prothrombin
prothrombin itself is normal
rare in non-caucasians
–> increased clot risk
What is hyperhomocysteinuria?
rare metabolic disorder
deficient trans sulphuration enzyme
increased homocysteine in blood and urine
increased risk of thrombosis and premature artherosclerosis
What is homocysteine?
amino acid
made from mehtionine
matins mylein
converts dietary folate
What is homocysteinuria?
rare metabolic disorder
Too much homocysteine leads to….
thrombosis
What causes homocysteinemia?
MTHFR gene mutation
homocysteinemia is d/t B12/folate def
What problems are caused by increased homocysteine?
Toxic to endothelium>
forms ROS which interfere with NO
What happens in heterozygous homocysteinemia?
increased thrombosis and premature athersclerosis
risk of venous thrombosis 2.5 x normal
risk of arterial thrombosis 10 x normal
What should you know about Antiphospholipid Ab?
Autoantibodies against phospholipids
Falsely prolong INR
may cause thromboses
antiphospholipid syndrome is serious
How does antiphospholipid Ab affect children, adults and the elderly?
children: infection mild risk
adults: autoimmune diseases, mod risk
elderly: drugs, no risk
What are the functions of antiphospholipid Abs?
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
What happens in antiphospholipid antibody syndrome?
recurrent thrombosis recurrent spontaneous abortions increased risk of stroke pulmonary hypertension renal failure
How do you detect Abs in antiphospholipid antibody syndrome?
- order a PTT
- if prolonged, order a PTT mixing study to see if PTT corrects or not
- If normal, antibody may still be present–> order fancy tests.
