Chapter 25: Thrombosis and antithrombotic therapy

Question 1

What is thrombophilia?

Answer 1

Thrombophilia are inherited or acquired disorders that predispose to thrombosis?

Question 2

What are the strongest independent predictors of coronary events?

Answer 2

The levels of factor VII and fibrinogen. Hyperhomocysteinemia has also been associated with increased risk.

Question 3

What is Virchow’s triad?

Answer 3

Virchow’s triad is composed of three components that are extremely important for thrombus formation.

(1) Slowing of blood flow
(2) hypercoagulability of the blood
(3) Vessel wall damage.

Question 4

What events suggest a hereditary thrombophilia?

Answer 4

Younger patients that suffer from spontaneous and recurrent thromboses in abnormal locations.

Question 5

What is the most common disorder that increases the risk of thrombosis?

Answer 5

Factor V leiden mutation. (4% of caucasians)

Question 6

With what protein deficiency is skin necrosis due to dermal vessel occlusion after warfarin administration associated?

Answer 6

Protein C deficiency

Question 7

Why does warfarin cause vessel occlusion associated with protein C deficiency?

Answer 7

Because Warfarin inhibits vitamin K dependent factors. Vitamin K is necessary for protein C to function.

Question 8

How does prothrombin allele G20210A lead to thrombophilia?

Answer 8

There is increased levels of prothrombin which leads to increased thrombin and down regulation of fibrinolysis.

Question 9

What enzyme is responsible for hyperhomocysteinemia?

Answer 9

A defect in cystathione beta synthase is responsible for hyperhomocysteinemia.

Question 10

What are some causes of acquired hyperhomocysteinemia?

Answer 10

(1) Folate or B12 deficiency
(2) B6 deficiency
(3) drugs (ciclosporin)
(4) renal damage.
(5) smoking.

Question 11

Do defects in fibrinogen lead to thrombosis?

Answer 11

Not usually, bleeding is more likely.

Question 12

What are some common acquired risk factors for thrombosis?

Answer 12

(1) surgical opperations
(2) Venous stasis and immobility
(3) Malignancy
(4) Inflammation
(5) polycythemia and ET
(6) increased estrogen

Question 13

What is antiphospholipid syndrome?

Answer 13

The occurrence of repeated thromboses/miscarriages with the presence of anti phospholipid antibodies. These antibodies are in some cases secondary to autoimmune disease.

Question 14

Why does glucosylceremide deficiency lead to thrombosis?

Answer 14

Because glucosylceremide modulates the protein C pathway.

Question 15

Why are factor IX concentrates sometimes complicated by thrombosis?

Answer 15

Because factor IX concentrates often contain activated coagulation factors.

Question 16

What factors should increase the clinical suspicion of deep vein thrombosis?

Answer 16

Bedridden patients with unilateral swelling or tenderness.

Question 17

What is the first line test when DVT is suspected?

Answer 17

Serial compression ultrasonography

Question 18

What is the second line test if ultrasonography is negative yet clinical signs point to DVT?

Answer 18

Contrast venography

Question 19

What is a plasma D-dimer concentration assay?

Answer 19

Plasma D-dimers are the breakdown products of fresh thromboses. They are elevated if DVT has occured. However they may be elevated in some other conditions as well.

Question 20

When should a pulmonary embolus be suspected?

Answer 20

When the patient has

(1) history of DVT
(2) immobilization for more than 2 Days
(3) surgery
(4) hemoptysis

Question 21

What methods may be used to diagnose pulmonary embolism?

Answer 21

(1) chest X-ray
(2) ventilation perfusion scintigraphy
(3) Computed tomography pulmonary angiographty
(4) MRI angiography
(5) Pulmonary angiography

Question 22

How is heparin administered?

Answer 22

intravenously

Question 23

How is heparin eliminated by the body?

Answer 23

Heparin is inactivated by the liver and excreted in the urine.

Question 24

What is the biological half-life of heparin?

Answer 24

Approximately 1 hour.

Question 25

What is heparin's mechanism of action?

Answer 25

Heparin potentiates the formation of complexes between antithrombin and thrombin, IXa, Xa, and XIa. This leads to the irreversible inactivation of these factors.

Question 26

What are the indications for Heparin?

Answer 26

(1) DVT (2) Pulmonary embolism (3) unstable angina pectoris (4) Prophylaxis during pregnancy (does not cross the placenta)

Question 27

What is the treatment of choice for acute pulmonary embolus?

Answer 27

Continuous intravenous heparin

Question 28

What is the preferred prophylacitic treatment for venous thrombosis?

Answer 28

Intermittent subcutaneous heparin.

Question 29

What is the difference between regular heparin and low molecular weight fractionated heparin?

Answer 29

LMWFH has a longer half life, more predictable dose response, and has less severe side effects (50% less side effects).

Question 30

What are some adverse effects associated with heparin?

Answer 30

(1) Bleeding (2) Heparin induced thrombocytopnenia (3) Osteoporosis (with more than 2 months use)

Question 31

What are the oral anticoagulants?

Answer 31

Derivatives of coumarin or indandione | Warfarin is most commonly used.

Question 32

What is the mechanism of warfarin?

Answer 32

Warfarin is a vitamin K antagonist.

Question 33

Between warfarin and heparin which one is preferred during pregnancy?

Answer 33

Warfarin is teratogenic therefore heparin is preferred because it does not cross the placenta.

Question 34

How is warfarin eliminated?

Answer 34

Warfarin is inactivated in the liver and then excreted in the bile.

Question 35

What drug interactions are important for Warfarin?

Answer 35

(1) alterations in albumin binding (warfarin is 97% bound (2) Interactions involving the excretion of warfarin (3) interactions altering vitamin K absorbtion

Question 36

What is protamine?

Answer 36

Protamine is able to inactivate heparin and can be used as an antidote in the event of heparin overdose/excessive bleeding.

Question 37

How can warfarin overdose be managed?

Answer 37

Giving vitamin K can overcome the effects of warfarin overdose.

Question 38

How is warfarin therapy managed during surgery?

Answer 38

For minor surgery tranexamine acid (an anti-fibrinolytic) can be used as a mouth rinse. However, for major surgery the warfarin must be stopped.

Question 39

What are the 'New' anticoagulants?

Answer 39

(1) fondaparinux (a factor Xa inhibitor) (2) Bivalirudin (thrombin inhibitor) (3) Ximelagraten (thrombin inhibitor

Question 40

What drugs can be used as thrombolytic agents?

Answer 40

(1) streptokinase (2) Acylated plasminogen streptokinase activator complex (APSAC) (3) tissue plasminogen activator (tPA) (4) Urokinase type plasminogen activator

Question 41

What are the antiplatelet agents that can be used to fight thrombosis?

Answer 41

(1) aspirin (irreversible COX inhibitor) (2) Dipryidamole (phosphodiesterase inhibitor) (3) Sulfinpyrazone (competitive inhibitor of COX) (4) Ticlopidine (is mostly replaced by clopodigrel) (5) Clopodigrel (ADP receptor antagonist)

Question 42

What are the GPIIb/IIIa inhibitors?

Answer 42

(1) abciximab (2) eptifibatide (3) tirofiban They can only be used once.