Hematological Agents II

Question 1

Type 1 HIT

Answer 1

Mild, transient thrombocytopenia
Not thought to be caused by immune system
Occurs 2-5 days after first treatment of heparin

Question 2

Type 2 HIT

Answer 2

Immune-related thrombocytopenia
Significant mortality
Causes venous and arterial thrombosis
Heparin binds platlets. Antibodies formed against those platelets. Platelets are actvated and cleared by macrophages

Question 3

What types of patients are more likely to develop HIT?

Answer 3

More common in surgical and cancer patients.

Question 4

LWHP
Name
MOA
Contraindication

Answer 4

Enoxaparin
Primarily acts as an indirect inhibitor of factor Xa
Contraindicated in patients with severe renal insufficiency

Question 5

Which heparin product is preferred for long-term use?

Is the heparin antidote effective against this agent?

Answer 5

LMWH (Enoxaparin) is preferred for long-term use

Protamine partially reverses effects of Enoxaparin

Question 6

ELMWH
Name
MOA
Contraindication
Antidote
Assay

Answer 6

Fondaparinux
Binds AT and increases activity towards Xa but does not bind thrombin
Contraindicated in patients with renal insuffiency
Protamine is ineffective
Anti-factor Xa assay is used for LMWH and fondaparinux

Question 7

Name all 4 DTIs
Which two are bivalent?
Which two are univalent?
Which are parental?
Which is oral?

Answer 7

Bivalirudin and lepirudin are bivalent
Dabigatran and argatroban are univalent
Bivalirudin, lepirudin, and argatroban are parental while dabigatran is oral

Question 8

DTI MOA

Answer 8

Bind to active site of thrombin (univalent) and fibrin binding site (bivalent) and completely inhibit thrombin from converting fibrinogen to fibrin
Only DTIs can inhibit thrombin bound to fibrin

Question 9

Antidote to DTIs

Answer 9

There isn’t one

Question 10

MOA for warfarin

Answer 10

Warfarin competes with vitamin K for vitamin K reductase thereby inactivating factors 2, 7, 9, 10, and proteins C and S

Question 11

How long until full anti-thrombin effect of warfarin begins? Solution to this?

Answer 11

3-5 days

Patients are supplemented with heparin, LMWH, or fondaparinux for the first 3-5 days

Question 12

Resistance to warfarin caused by? (2)

Answer 12

1. Common genetic variants of CYP2C9

2. Polymorphisms in Vitamin K reductase

Question 13

What is the assay for warfarin therapy?
Target range?
Purpose?

Answer 13

International normalizes ratio (INR)
2.0-3.0
Purpose is to normalize PT

Question 14

4 drugs that potentiate warfarin (increase INR)

Answer 14

Broad spectrum abx
NSAIDs
SSRI (some)
Statins (some)

Question 15

3 drugs that inhibit warfarin (decrease INR)

Answer 15

Rifampin
Barbituates
Carbamazepine

Question 16

3 other factors that potentiate warfarin

Answer 16

1. Decreased hepatic clearance of warfarin
2. Intestinal disease that decrease vitamin K absorption
3. Renal insufficiency causing hypoalbuminemia

Question 17

Warfarin contraindicated in which two populations

Answer 17

Pregnant

Patients with low protein C levels…can cause warfarin induced skin necrosis

Question 18

Warfarin antagonists and time frame

Answer 18

1. Vitamin K (slow)

2. Fresh plama (fast)

Question 19

Two Xa inhibitors

Answer 19

Rivaroxaban

Apixaban

Question 20

Advantages of Xa Inhibitors over warfarin (3)

Answer 20

1. Faster onset
2. Larger therapeutic window
3. Lower risk of a brain bleed

Question 21

Name the fibrinolytic drug and clinical uses (2)

Answer 21

Alteplase- recombinant human tPA that activates plasminogen to plasmin
Used for acute MI and acute thrombotic stroke

Question 22

Fibrinolytic inhibitors (2)

Answer 22

Aminocaproic Acid

Tranexamic Acid

Question 23

Fibinolytic inhibitor MOA

Answer 23

Block interaction of plasmin with fibrin