Thrombophilia and Anticoagulant Therapy

Question 1

Discuss the mechanism by which coagulation is inhibited by tissue factor pathway inhibitor (TFPI)

Answer 1

• Inhibits the TF pathway by inactivating Factor VIIa

- Due to the action of TFPI: TF-VIIa is short lived and coagulation amplification occurs primarily through XI

Question 2

Origin of Protein C (and Protein S)

Answer 2

Synthesized in the liver

Question 3

What are Protein C and S dependent upon?

Answer 3

Vitamin K

Question 4

What is the principle of Protein C and S by which coagulation is inhibited and affected factors?

Answer 4

It inactivates Va and VIIIa and may cause recurrent thromboses (blood clot)

Question 5

State the mutation that is responsible for the most commonly inherited form of thrombophilia

Answer 5

Activated Protein C resistance (APCR) → called Factor V Leiden mutation

Question 6

Origin of antithrombin

Answer 6

Liver

Question 7

Is antithrombin dependent upon Vitamin K?

Answer 7

No

Question 8

Principle of antithrombin (AT) by which coagulation is inhibited, including affected factors

Answer 8

• Serine protease inhibitor (SERPIN)

- Irreversibly binds and neutralizes the serine proteases `in the intrinsic pathways: XIIa, XIa, IXa, Xa, thrombin (IIa)

Question 9

In the antithrombin, when no heparin is present, AT’s binding w/ the serine proteases is a ____ reaction

Answer 9

Slow, progressive

Question 10

When either endothelial cell heparan or exogenously administered ____ is present, ____ binding w/ the serine proteases is ____ and enhanced 1,000-fold!!

Answer 10

Heparin is present; AT’s binding; immediate

Question 11

The effect of deficiency states of antithrombin (AT) and protein C (protein S)

Answer 11

May cause recurrent thromboses

Question 12

Eight factors that predispose a person to thrombosis

Answer 12

• Age
• Hereditary
• Immobilization/stasis
• Smoking
• Malignancy
• Injury to vessels (trauma, surgery)
• Elevated estrogens (low protein S, C, AT)
• Inflammation
• Antiphospholipid syndrome

Question 13

Three types of thomboses

Answer 13

• Arterial thromboses
• Microcirculatory (TTP, HUS, DIC)
• Venous thromboses

Question 14

What is the process by which arterial thrombosis are formed?

Answer 14

Result of a disease process which causes major damage in a vessel wall (myocardial infarction, arteriosclerosis)

Question 15

Arterial thrombosis

- Major component

Answer 15

Platelets

Question 16

Arterial thrombosis

- Treatment

Answer 16

Anti-platelet drugs (aspirin, plavix)

Question 17

Process by which venous thrombosis are formed?

Answer 17

Result of a major stasis in blood flow (DVT, pulmonary embolus)

Question 18

Venous thrombosis

- Major component

Answer 18

Fibrin

Question 19

Venous thrombosis

- Treatment

Answer 19

Antifibrin drugs (heparin, coumadin)

Question 20

Defined as a predisposition of thrombosis secondary to a congenital or acquired disorder

Answer 20

Thrombophilia

Question 21

Defined as the inappropriate formation of platelet or fibrin clots that obstruct vessels

Answer 21

Thrombosis

Question 22

Defined as any foreign object in the bloodstream such as air, bullet, clot

Answer 22

Embolus

Question 23

Four types of anticoagulant therapy

Answer 23

• Standard unfractionated heparin (UFH)
• Low molecular weight heparin (LMWH)
• Coumadin drugs
• Thrombolytic agents (clot busters)

Question 24

Standard unfractionated heparin (UFH)

- Mechanism of action

Answer 24

Heparin by itself is NOT and anticoagulant must complex w/ AT and ATP is called the “heparin co-factor”

Question 25

Standard unfractionated heparin (UFH) | - Indication for therapy

Answer 25

Treatment of thrombosis to prevent propagation

Question 26

Standard unfractionated heparin (UFH) | - Administration

Answer 26

IV or subcutaneously (SQ)

Question 27

Standard unfractionated heparin (UFH) | - Monitoring

Answer 27

APTT - Target for therapy - Prophylaxis - Daily platelet counts to detect HIT

Question 28

Standard unfractionated heparin (UFH) | - Overdose

Answer 28

Treat w/ protamine sulfate

Question 29

Low molecular weight heparin (LMWH) | - Mechanism of action

Answer 29

Increases the inhibitor effect of AT on thrombin and Xa (mainly Xa)

Question 30

Also known as Lovenox

Answer 30

Low molecular weight heparin (LMWH)

Question 31

Low molecular weight heparin (LMWH) | - Administration

Answer 31

SQ

Question 32

Low molecular weight heparin (LMWH) | - Indication for therapy

Answer 32

Treatment of thrombosis to prevent propagation; not as commonly used but great for those needing to go home on heparin

Question 33

Low molecular weight heparin (LMWH) | - Monitoring

Answer 33

Anti-Xa heparin assay (APTT is insensitive)

Question 34

Why is monitoring Low molecular weight heparin (LMWH) necessary?

Answer 34

For infants, children, obese or underweight patients, those w/ renal disease, or unexpected bleeding

Question 35

Which brand is most common for long-term anticoagulant therapy?

Answer 35

Coumadin

Question 36

Which brand is the oldest brand name for long-term anticoagulant therapy

Answer 36

Warfarin

Question 37

Coumadin | - Mechanism of action

Answer 37

Coumadin blocks the action of vitamin K which is needed for the synthesis of the vitamin K dependent factors. Therefore, slowing thrombin formation

Question 38

What are the vitamin K dependent factors?

Answer 38

Prothrombin group (II, VII, IX, X)

Question 39

Coumadin | - Administration

Answer 39

Oral

Question 40

Coumadin | - Delayed reaction or immediate reaction?

Answer 40

Delayed reaction (3-5 days)

Question 41

Coumadin | - Indication for therapy

Answer 41

Treatment of thrombosis to prevent propagation; prevention of thromboembolic disease in thrombophilia, mechanical heart valves, and high risk surgery.

Question 42

Coumadin | - Monitoring

Answer 42

PT and INR

Question 43

Coumadin | - Overdose

Answer 43

Treat by giving vitamin K and FFP if major bleeding

Question 44

Standard Unfractionated Heparin (UFH) | - Immediate or delayed reaction?

Answer 44

Immediate reaction

Question 45

List sources of vitamin K

Answer 45

- Diet: green leafy vegetables, fish, and liver | - Normal gut flora: E. coli, B. fragilis

Question 46

Three situations in which vitamin K deficiency may occur

Answer 46

- Poor diet - Long-term antibiotic therapy - Newborns

Question 47

Vitamin K makes the prothrombin factors functional by ____

Answer 47

By adding a 2nd carboxyl group on the γ carbon. In vitamin K deficiency or in the presence of a vitamin K antagonist, these factors are released from the liver without the γ-carboxylation rendering them nonfunctional

Question 48

``` Thrombolytic agents (clot busters) - Mechanism of action ```

Answer 48

Indiscriminately induce in vivo fibrinolysis by activating plasminogen to plasmin; not only get rid of bad clots but good clots too

Question 49

Types of thrombolytic agents

Answer 49

- Tissue plasminogen activator (TPA) - Streptokinase - Urokinase

Question 50

Why is TPA considered the best/safest clot buster?

Answer 50

B/c it will NOT activate circulating (free) plasminogen...only fibrin bound

Question 51

When is the therapeutic agent TPA used?

Answer 51

- Life threatening thromboses | - Must be given w/in 4-6 hours of onset