Thrombotic Disorders - Krafts Flashcards
What are the risk factors associated with atherosclerosis?
Hypertension
Hyperlipidemia
Obesity
Smoking
What are the risk factors for Thrombosis?
Endothelial Damage (Atherosclerosis)
Stasis
Hypercoagulability
What are the risk factors associated with stasis?
Immobilization
Varicose Veins
Cardiac Dysfunction
What are the risk factors associated with Hypercoagulability?
Trauma/Surgery
Carcinoma
Estrogen/Postpartum
Thrombotic Disorders
What are the characteristics of Factor V Leiden?
Most common cause of unexplained thromboses
Seen in Caucasians
What is Factor V Leiden?
Point mutation in Factor V gene
Factor V can’t be turned off/can’t be cleaved by Protein C
How do you diagnose Factor V Leiden?
Genetic Testing
How do you treat Factor V Leiden?
Don’t unless there is a thrombosis.
If thrombosis, then give anti-coagulant (coumadin) for a little while or if other risk facters, anti-coagulate for life
What are the characteristics of Antithrombin III Deficiency?
Very Rare!
Lots of gene mutations exist
What is Antithrombin III Deficiency and what is it potentiated by?
ATIII is a natural anticoagulant that is potentiated by heparin
What is the deficiency in the ATIII gene?
Mutated gene produces less ATIII, but no genetic testing available
What is the risk of getting a clot?
Homozygotes: Can’t survive
Heterozygotes: Half get clots
Heparin won’t work
Antithrombin concentrates required
What are the characteristics of Protein C and S deficiencies?
Protein C deficiency is rare
Protein S deficiency is super-rare
What is Protein S?
Natural anticoagulant
What is Protein C?
Natural anticoagulant: Inactivates Va and VIIIa
Fibrinolytic: Promotes t-PA action
Anti-inflammatory: Keeps cytokines low
What is the outcome of Protein C and S Deficiencies?
Warfarin-induced skin necrosis
Purpura Fulminans
What’s wrong with the Protein C gene?
Mutated gene produces less Protein C or a defective Protein C
–> due to many different mutations
How do you diagnose Protein C Deficiency?
Functional Testing
What does coumadin inhibit?
Factor II, VII, IX, and X
Proteins C and S
What is Purpura Fulminans?
Thrombotic State with Vascular Injury resulting in skin necrosis associated with Protein C and S deficiency and sepsis
What is the treatment of Purpura Fulminans?
Protein C
What are the characteristics of Factor II (Prothrombin) Gene Mutation?
Makes too much normal prothrombin
Common in Caucasians
What are the characteristics of Hyperhomocysteinemia?
Too much homocysteine results in thromboses
What does homocysteine do?
Converts folate to THF using B12/MS to make methionine
What is homocysteine?
Amino Acid
Made from Methionine
Maintains Myelin
Converts dietary folate
What is Homocysteinuria?
Rare Metabolic Disorder
Mutation in CBS (Cystathionine Beta Synthase)
Increased homocyteine in blood/urine
Increased thrombosis and premature atherosclerosis
What is the pathogenic cause of Homocysteinemia?
Mutation in MTHFR gene (methylene tetrahydrofolate reductase)
B12/Folate Deficiency
What’s so bad about homosysteine?
Toxic to Endothelium that forms reactive oxygen species
Interferes with nitric oxide (antithrombotic and vasodilator)
What results from heterozygous homocysteinemia?
Increased thrombosis, premature atherosclerosis
What is the acquired thrombotic disorder?
Antiphospholipid Antibody
What are the characteristics of Antiphospholipid Antibodies?
Falsely prolonged INR
May cause thromboses
What are Antiphospholipid Antibodies?
IgG antibodies against phospholipids = Inhibitors
What are the 3 variants of Antiphospholipid Antibodies?
Anticardiolipin Antibodies
Lupus Anticoagulants
Antibodies against other molecules
What coagulation tests do Antiphospholipid Antibodies screw up?
Bind to PTT/PT reagent
Can’t clot
Results are prolonged
What other tests can Antiphospholipid Antibodies screw up?
Syphilis Test
Direct Antiglobulin Test
In vivo, what do antiphospholipid antibodies do?
Promote Coagulation
In vitro, what do antiphospholipid antibodies do?
Inhibit Coagulation
Who is most likely to develop antiphospholipid antibodies?
Adults with autoimmune diseases
What symptoms are associated with Antiphospholipid Antibody Syndrome?
Recurrent Thrombosis Recurrent Spontaneous Abortions Increased risk of Stroke Pulmonary Hypertension Renal Failure
How do you diagnose Antiphospholipid Antibodies?
PTT: Prolonged
PTT Mixing Study: not corrected
