Hereditary and Acquired Thrombotic Disorders

Question 1

What test is used to diagnose a venous thrombosis?

Answer 1

D dimer test. Then a spiral CT and a V/Q scan with diminished perfusion

Question 2

What are some common risk factors for acquired thrombotic disorders?

Answer 2

• Malignancy
• Hematologic Disorders
• Incleased clotting factors (Factors VII, VIII, XI)
• DIC
• Vasculitic/Proinflammatory Disorders

Question 3

What are four inherited hypercoagulable disorders?

Answer 3

1) Antithrombin Deficiency
2) Factor V Leiden
3) Protein C Deficiency
4) Protein S Deficiency

Question 4

What are the most common clinical presentations of pulmonary embolisms?

Answer 4

Dyspnea, Increased respiratory rate, Increased heart rate, Chest Pain, Cough, Syncope

Question 5

What are the 3 components of Virchow’s Triad?

Answer 5

1) Decreased blood flow (venous stasis)
2) Inflammation of or near the blood vessels (altered vessels)
3) Intrinsic alterations in the nature of the blood itself (altered coagulability)

Question 6

What are the 3 clinical symptoms of a leg thrombosis?

Answer 6

1) Edema and pain (there is impaired venous return, the pain comes from increased hydrostatic pressure)
2) Dilated superficial veins (because blood finds a different route to get back to heart)
3) Redness and warmth in area (thrombus triggers inflammatory response)

Question 7

What is phlegmasia cerulean dolens?

Answer 7

An extremely blue swollen painful leg. It’s caused by complete obstruction of the proximal vein for venous outflow.

Question 8

What color do arterial clots tend to be? Venous clots?

Answer 8

Arterial clots tend to be white, whereas venous clots tend to be red b/c they get RBCs caught in them.

Question 9

Compare and contrast the factors that can cause altered coagulability of arterial vs. venous clots

Answer 9

Arterial: platelet activation, hyperviscosity, thrombocytosis.
Venous:

Question 10

Contrast the primary composition of arterial vs. venous clots

Answer 10

Arterial: composed primarily of platelets
Venous: composed of clotting factors and fibrinogen

Question 11

What are the 3 main classes of antithrombotic agents?

Answer 11

1) Heparins
2) Vitamin K antagonists (warfarin)
3) Direct thrombin inhibitors (hirudins)

Question 12

List clinical clues that suggest an inherited hypercoagulable disorder

Answer 12

1) First thrombosis age (if

Question 13

What does warfarin inhibit and what is used to determine whether or not it is working?

Answer 13

Warfarin blocks Vitamin K from activating some of the factors, including factors II, VII, IX, and X as well as Proteins C and Protein S.
Prothrombin time is used to monitor warfarin because Factor VII has the shortest half life (5 hours)

Question 14

What is the pattern of inheritance of Factor V Leiden and how do you test for it?

Answer 14

Autosomal Dominant.

You do DNA analysis for heterozygotes vs homozygotes

Question 15

What is wrong in Factor V Leiden?

Answer 15

Protein C normally inactivates Factor Va to Factor V. In Factor V Leiden, the Factor Va is resistent to inactivation and is inactivated 10x slower than normal

Question 16

What are the 2 results of Factor V Leiden?

Answer 16

1) Increased coagulation-there is more Factor Va in circulation so more thrombin can be generated
2) Decreased anticoagulation-normally Factor V is a cofactor for Protein C, but since there is less, there can’t be as much anticoagulation (APC resistance)

Question 17

What is the relative risk in Factor V Leiden in one gene mutation and two gene mutations?

Answer 17

One gene mutation=4-7x increased risk

Two mutations=50-80x increased risk

Question 18

Give the specifics of the prothrombin gene mutation

Answer 18

• it’s a genetic polymorphism that results in increased prothrombin in circulation
• autosomal dominant
• occurs in 2-3% of caucasian population
• associated with VENOUS thrombosis
• most people don’t actually clot with this condition
• 2-3x risk for heterozygotes, homozygotes unknown

Question 19

Differentiate between Type I and Type II antithrombin deficiency. What does antithrombin typically do?

Answer 19

Type I=decreased protein, Type II=decreased protein activity.
Antithrombin normally binds and neutralizes factors II, IX, and X which are procogulators

Question 20

What are some of the results of antithrombin deficiency?

Answer 20

• Venous thromboses, 60% of people have recurrent venous thromboses
• Rare before puberty but usually before age 50
• Can get other acquired problems such as: DIC, Liver disease, nephrotic syndrome, acute thrombosis

Question 21

Fast facts on Protein C deficiency. GO!

Answer 21

• Autosomal dominant
• Homozygosity leads to neonatal purpura fulminans
• Heterozygotes are affected 75% of the time
• Tested by testing the protein function, not presence

Question 22

Protein S deficiency time.

Answer 22

• it’s a cofactor of Protein C so it has a lot of the same affects.
• unlike Protein C, it’s best to test for Protein S levels, those are most indicative of problems.

Question 23

What do we do with the asymptomatic carriers?

Answer 23

Normally they don’t need treatment, but there are some things (surgery, pregnancy, etc.) that might set them off so they should be aware.
If they’re on birth control they should be put on anticoagulants.

Question 24

What are the clinical symptoms of antiphospholipid antibody syndrome? (sorry guys, I’m fading so these aren’t creative at all)

Answer 24

• there are antibodies that cause obsetric or clotting issues
• venous and arterial thromboses possible
• not age, gender, or location specific
• cerebral ischemia is a possibility
• MS like symptoms
• migraines
• related to drug exposure, infection, and illness

Question 25

What laboratory criteria is necessary to diagnose antiphopholipid antibody syndrome?

Answer 25

• 2 positive tests at least 12 weeks apart

- -either lupus anticoagulant (LA), Anticardiolipin antibodies (ACA), or Beta2GP-1

Question 26

What’s the key difference in treatment for venous vs. arterial thromboses?

Answer 26

Arterial-use antiplatelet therapy

Venous-use anticoagulant therapy

Question 27

Oh no! You just discovered an arterial clot in your patient who has antiphopholipid antibody syndrome! What should you treat them with?

Answer 27

• Unclear. Warfarin probably, although ASA could work too.

* ASA for asymptomatic, warfarin for venous clots, heparin and ASA for people who have recurrent miscarriages.