Clotting disorders Flashcards
thrombosis =
an abnormal clot
thrombosis risk factors
Endothelial damage
Stasis
Hypercoagulability
Endothelial damage is a result of
often atherosclerosis (hypertension, hyperlipidemia, smoking, obesity)
Stasis
Immobilization
varicose veins
cardiac dysfunction
Hypercoagulability
Trauma/surgery
Carcinoma
Estrogen/postpartum
Thrombotic disorder
When should you worry and your patient has a throbmus?
No obvious cause Family history weird location recurrent young patient miscarriages
Hereditary thrombotic disorders
Factor V Leiden ATIII deficiency Protein C deficiency Protein S deficiency Factor II gene mutation Homocysteinemia
Acquired thrombotic disorder
Antiphospholipid Ab
About Factor V Leiden
Most common cause of unexplained thromboses
Point mutation in factor V gene
Factor V cannot be turned off
Need GENETIC testing for diagnosis
What happens when point mutation occurs in Factor V?
Participation in clotting cascade is not stopped because V cannot be cleaved by protein C
How common is factor V leiden?
Half of patients with unexplained thrombosis
5% of caucasians
Risk of getting a clot with Factor V Leiden?
Heterozygotes 7x normal
Homozygotes 80x normal
How do you diagnose Factor V Leiden?
PTT and INR are not helpful (will be normal, cascade will be fine, test stops when fibrin forming)
GENETIC TESTING
How do you treat Factor V Leiden?
Don’t.. unless thrombosis
Then: anticoag for awhile
If multiple episodes (or other risk factors) long term anticoag
AT III deficiency - about
At III is a natural coag
Potentiated by heparin
Lots of gene mutations exist
Very rare
Antithrombin III
Natural anti coag
Inhibits IIa, VIIa, IXa, Xa, XIa (no PCR assay)
Potentiated by heparin
What is wrong with the AT III gene?
Mutated gene produces less ATIII
Rare
No genetic testing
Risk of clots in AT III deficiency
Homozygotes - fatal
Heterozygotes - half get clots
Heparin won’t work
Antithrombin concentrates required
Protein C and S deficiencies
Natural coagulants
C is also fibrinolytic and anti inflammatory
warfarin induced skin necrosis
C deficiency is rare, S super rare
Protein C
anticoagulant - Inactivates Va and VIIIa
Fibrinolytic - promotes t-PA action
anti-inflammatory - keeps cytokine levels low
What is wrong with gene in protein C deficiency
Mutated gene produces less protein C (or defective)
Diagnosis via functional testing
Risk of clots in protein C deficiency
7x normal (heterozygotes) Unique risks: warfarin skin necrosis, purpura fulminans
Coumadin and Protein C
Coumadin wipes out protein C quickly because short half life
Coumadin and protein C deficiency
Be careful - coumadin wipes out protein C and become hypercoagulable
Purpura Fulminans
Thrombotic state + vascular injury
Net result : skin necrosis
Associated with : protein C and S def. and sepsis
Treatment: protein C (last resort)
Protein S deficiency
So rare, same as C
Factor II
prothrombin
Factor II gene mutation
makes too much prothrombin
Hyperhomocysteinemia
too much cysteine - thromboses
MTHFR mutation
B12/folate deficiency
not so rare
Homocysteinuria
Rare metabolic disorder
What is so bad about cysteine (in context of hyperhomocysteinemia)
Toxic to endothelium by forming ROS and Interferes with NO (visodilator and antithrombotic)
Heterozygous homocysteinemia
Increase thrombosis, premature atherosclerosis (venus 2x risk, arterial 10x normal risk)
homocysteinemia in B12 deficiency
less worrisome but still need to watch for other risk factors
Antiphospholipid Antibodies
Autoantibodies against phospholipids
Falsely prolonged INR
May cause thromboses
Antiphospholipid syndrome is serious
What are antiphospholipid ab?
IgG ab against phospholipids 3 variants (anticadiolipin, lupus anticoag, antibodies against other molecules)
What do antiphospholipid ab do?
Bind to phospholipids
Screw up coag tests (bind up PTT, PT reagents so spec. cannot clot, test results appear prolonged)
Screw up DAT and syphilis tests
Antiphospholipids ______ coagulation in vivo
promote
Antiphospholipids ______ coagulation in viro
Inhibit
Who develops antiphospholipid ab?
Children (infection - mild risk)
Adults (autoimmune disorders - moderate risk)
Elderly (drugs - no risk)
Antiphospholipid Antibody Syndrome
Recurrent thrombosis Recurrent Spontaneous Abortions Increased Risk of Stroke Pulmonary HT Renal failure
