Thrombotic Disorders - Krafts

Question 1

What are the risk factors associated with atherosclerosis?

Answer 1

Hypertension
Hyperlipidemia
Obesity
Smoking

Question 2

What are the risk factors for Thrombosis?

Answer 2

Endothelial Damage (Atherosclerosis)
Stasis
Hypercoagulability

Question 3

What are the risk factors associated with stasis?

Answer 3

Immobilization
Varicose Veins
Cardiac Dysfunction

Question 4

What are the risk factors associated with Hypercoagulability?

Answer 4

Trauma/Surgery
Carcinoma
Estrogen/Postpartum
Thrombotic Disorders

Question 5

What are the characteristics of Factor V Leiden?

Answer 5

Most common cause of unexplained thromboses

Seen in Caucasians

Question 6

What is Factor V Leiden?

Answer 6

Point mutation in Factor V gene

Factor V can’t be turned off/can’t be cleaved by Protein C

Question 7

How do you diagnose Factor V Leiden?

Answer 7

Genetic Testing

Question 8

How do you treat Factor V Leiden?

Answer 8

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

Question 9

What are the characteristics of Antithrombin III Deficiency?

Answer 9

Very Rare!

Lots of gene mutations exist

Question 10

What is Antithrombin III Deficiency and what is it potentiated by?

Answer 10

ATIII is a natural anticoagulant that is potentiated by heparin

Question 11

What is the deficiency in the ATIII gene?

Answer 11

Mutated gene produces less ATIII, but no genetic testing available

Question 12

What is the risk of getting a clot?

Answer 12

Homozygotes: Can’t survive
Heterozygotes: Half get clots
Heparin won’t work
Antithrombin concentrates required

Question 13

What are the characteristics of Protein C and S deficiencies?

Answer 13

Protein C deficiency is rare

Protein S deficiency is super-rare

Question 14

What is Protein S?

Answer 14

Natural anticoagulant

Question 15

What is Protein C?

Answer 15

Natural anticoagulant: Inactivates Va and VIIIa
Fibrinolytic: Promotes t-PA action
Anti-inflammatory: Keeps cytokines low

Question 16

What is the outcome of Protein C and S Deficiencies?

Answer 16

Warfarin-induced skin necrosis

Purpura Fulminans

Question 17

What’s wrong with the Protein C gene?

Answer 17

Mutated gene produces less Protein C or a defective Protein C
–> due to many different mutations

Question 18

How do you diagnose Protein C Deficiency?

Answer 18

Functional Testing

Question 19

What does coumadin inhibit?

Answer 19

Factor II, VII, IX, and X

Proteins C and S

Question 20

What is Purpura Fulminans?

Answer 20

Thrombotic State with Vascular Injury resulting in skin necrosis associated with Protein C and S deficiency and sepsis

Question 21

What is the treatment of Purpura Fulminans?

Answer 21

Protein C

Question 22

What are the characteristics of Factor II (Prothrombin) Gene Mutation?

Answer 22

Makes too much normal prothrombin

Common in Caucasians

Question 23

What are the characteristics of Hyperhomocysteinemia?

Answer 23

Too much homocysteine results in thromboses

Question 24

What does homocysteine do?

Answer 24

Converts folate to THF using B12/MS to make methionine

Question 25

What is homocysteine?

Answer 25

Amino Acid Made from Methionine Maintains Myelin Converts dietary folate

Question 26

What is Homocysteinuria?

Answer 26

Rare Metabolic Disorder Mutation in CBS (Cystathionine Beta Synthase) Increased homocyteine in blood/urine Increased thrombosis and premature atherosclerosis

Question 27

What is the pathogenic cause of Homocysteinemia?

Answer 27

Mutation in MTHFR gene (methylene tetrahydrofolate reductase) B12/Folate Deficiency

Question 28

What's so bad about homosysteine?

Answer 28

Toxic to Endothelium that forms reactive oxygen species | Interferes with nitric oxide (antithrombotic and vasodilator)

Question 29

What results from heterozygous homocysteinemia?

Answer 29

Increased thrombosis, premature atherosclerosis

Question 30

What is the acquired thrombotic disorder?

Answer 30

Antiphospholipid Antibody

Question 31

What are the characteristics of Antiphospholipid Antibodies?

Answer 31

Falsely prolonged INR | May cause thromboses

Question 32

What are Antiphospholipid Antibodies?

Answer 32

IgG antibodies against phospholipids = Inhibitors

Question 33

What are the 3 variants of Antiphospholipid Antibodies?

Answer 33

Anticardiolipin Antibodies Lupus Anticoagulants Antibodies against other molecules

Question 34

What coagulation tests do Antiphospholipid Antibodies screw up?

Answer 34

Bind to PTT/PT reagent Can't clot Results are prolonged

Question 35

What other tests can Antiphospholipid Antibodies screw up?

Answer 35

Syphilis Test | Direct Antiglobulin Test

Question 36

In vivo, what do antiphospholipid antibodies do?

Answer 36

Promote Coagulation

Question 37

In vitro, what do antiphospholipid antibodies do?

Answer 37

Inhibit Coagulation

Question 38

Who is most likely to develop antiphospholipid antibodies?

Answer 38

Adults with autoimmune diseases

Question 39

What symptoms are associated with Antiphospholipid Antibody Syndrome?

Answer 39

``` Recurrent Thrombosis Recurrent Spontaneous Abortions Increased risk of Stroke Pulmonary Hypertension Renal Failure ```

Question 40

How do you diagnose Antiphospholipid Antibodies?

Answer 40

PTT: Prolonged | PTT Mixing Study: not corrected