Thrombophilia Flashcards
The optimal laboratory evaluation for thrombophilia taks place ______ following the acute episode and ____ following cessation of anticoagulant therapy.
> 2 months
>14 days
What are the most common Genetic tests for thrombophilia?
- Prothrombin 20210 mutation testing
- Factor V Leiden mutation testing
What is Factor V Leiden?
Activated protein C (APC) resistance
What is the normal function of activated protein C (APC)?
Inhibits coagulation by degrading:
-aFV (5) and aFVIII (8)
Factor V Leiden (APC resistance):
- Gene
- Mutation
- Inheritance
- Effect
- Factor V gene
- Glutamine for Arginine at position 506 (R506Q)
- Autosomal dominant
- Factor V Leiden is Resistant to cleavage by APC
Factor V Leiden is responsible for what percentage of cases of hereditary thrombophilia?
50%
Increased risk of thrombosis in Factor V Leiden:
- Heterozygotes
- Homozygotes
- 5-10X in Heterozygotes
- 50-100X in Homozygotes
What is the mutation in Prothrombin Variant?
-Results in what
G20210A of the Prothrombin gene
-Increased levels of Prothrombin
What are the most common complications in Factor V Leiden? (2)
- Venous Thromboembolism
- Recurrent miscarriage
What are the most common complications in Prothrombin G20210A mutation? (3)
- Venous Thromboembolism
- Cerebral Vein Thrombosis*
- Miscarriage
*Particularly high risk for Cerebral Vein Thrombosis
What factors are inhibited by Antithrombin (AT)? (5)
- 2
- 9a
- 10a
- 11a
- 12a
What does heparin do to Antithrombin activity?
Enhances it
*basis for the anticoagulant effect
What is the role of Protein S?
Cofactor of Protein C*
*Protein C degrades activated F5/F8 - Inhibits coagulation
FactorXII (12) deficiency lab findings. (2)
- Prolonged aPTT (Marked)
- Mixing study initially corrects, but is prolonged following incubation
The antiphospholipid (APL) syndrome encompasses what syndromes?
- Lupus Anticoagulant (LAC) syndrome
- Anticardiolipin Antibody (ACA) syndrome
Which is more common Lupus Anticoagulant (LAC) syndrome or Anticardiolipin Antibody (ACA) syndrome?
ACA
Which causes prolonged aPTT - Lupus Anticoagulant (LAC) syndrome or Anticardiolipin Antibody (ACA) syndrome?
LAC
What features are unique to Anticardiolipin Antibody (ACA) syndrome? (4)
- Premature Coronary Athersclerosis
- Livedo Reticularis
- Postpartum syndrome
- Warfarin Resistance
LAC tests are what?
Clot Based Assays
-Prolong phospholipid dependent clotting times, with failure to correct in 1:1 mix
ACA tests are what?
ELISA based assays
-High titer IgG ACA is significant
What conditions cause a false positive ACA test? (3)
- Syphilis
- Q fever
- HIV infection
*Usually IgM ACA
Type I Heparin Induced thrombocytopenia (HIT):
- Manifestations
- Incidence
- Immune-mediated?
Early and Mild Thrombocytopenia
- Plt decrease by day 1/2
- Plt count does NOT decrease beneath 50% baseline
Type I Heparin Induced thrombocytopenia (HIT):
- Incidence
- Immune-mediated?
- 5% of heparinized patients
- NOT immuned mediated
Type 2 Heparin Induced thrombocytopenia (HIT):
- Onset
- Effect (2)
- Incidence
- Immune Mediated?
- Days 5-14
- Plt count <50% of baseline
- High Risk of Thrombosis
- 1% of Heparinized pts
- Immune mediated
Types of Thrombosis in Type 2 HIT. (4)
- Arterial Thrombosis
- Venous Thrombosis
- Microvascular Thrombosis*
- Skin Necrosis/Erythematous Plaques at Heparin Injection site
*Coumadin (Warfarin) Contraindicated in HIT
Risk factors for Type 2 HIT. (2)
- Surgery (3-5X)
- Females (2X)
Diagnostic Test for Type 2 HIT?
Anti-PF4 Antibody test by ELISA
-90% sensitive/specific
What are the confirmatory tests for Type 2 HIT? (2)
- Serotonin Release Assay (SRA)
- Heparin Induced Platelet Aggregation Assay HIPA)
What are the types of Thrombotic Thrombocytopenia Purpura (TTP)? (3)
- Idiopathic
- Secondary TTP (pregancy, BMTx, Meds)
- Familial (Upshaw-Shulman syndrome)
Thrombotic Thrombocytopenia Purpura (TTP) Pentad.
- Thrombocytopenia
- Microangiopathic Hemolytic Anemia
- Neurologic changes
- Renal abnormalities
- Fever
Thrombotic Thrombocytopenia Purpura (TTP) lab findings. (3)
- Platelets <20,000
- Schistocytes (Numerous)
- High serum LDH (>1000 IU/dL)
Pathophysiology of TTP.
Deficient ADAMTS-13
-Abnormally large circulating multimers of vWF
What enzyme is responsible for cleaving large vWF multimers into smaller ones?
ADAMTS-13
What is the treatment for TTP?
-Contraindicated
Daily plasmapheresis with replacement of FFP
-Platelet transfusions are CONTRAINDICATED
