Anti-Coagulants

Question 1

List the 4 kinds or classes of anti-coagulants.

Answer 1

Indirect thrombin inhibitors, vitamin K antagonists, direct thrombin inhibitors, and direct Xa inhibitors

Question 2

List the 5 indirect thrombin inhibitors. Which molecule in the cell do they all bind to achieve their therapeutic effects?

Answer 2

Unfractionated heparin, dalteparin, enoxaparin, tinzaparin, and fondaparinux; all bind to antithrombin

Question 3

Which 3 of the indirect thrombin inhibitors are LMWH (low molecular weight heparins)? What molecule do they inhibit by binding to antithrombin?

Answer 3

Dalteparin, enoxaparin, and tinzaparin; inhibit Xa (not thrombin)

Question 4

Which “indirect thrombin inhibitor” forms an antithrombin-coagulation factor complex that actually inhibits both Xa and IIa (thrombin)?

Answer 4

Unfractionated heparin

Question 5

Which indirect thrombin inhibitor is the drug of choice for preventing venous thromboembolism in pregnant patients?

Answer 5

Enoxaparin

Question 6

Which indirect thrombin inhibitor inhibits Xa, has the long half life of 17-21 hours, and has no antidote? What kind of patients is it mainly given to?

Answer 6

Fondaparinux; given to patients with a history of HIT (heparin-induced thrombocytopenia)

Question 7

List 3 common side effects of using unfractionated heparin. Are these side effects shared by the LMWHs and fondaparinux?

Answer 7

Bleeding, HIT (heparin-induced thrombocytopenia), and osteoporosis (with long-term use);
They can all cause bleeding, but HIT and osteoporosis are less common with LMWH and are absent with fondaparinux

Question 8

Compare the administration, half life, and predictability of the dose-response curve for unfractionated vs. low-molecular weight heparin.

Answer 8

Unfractionated heparin has to be given parenterally and continuously in the hospital b/c it has a half life of 1 hour and is extremely unpredictable.
LMWH is more predictable and has a much longer half life, so it can be injected subcutaneously at home.

Question 9

Compare the monitoring methods and available antidotes for unfractionated heparin, LMWH, and fondaparinux.

Answer 9

Unfractionated heparin is monitored via PTT while LMWH and fondaparinux are monitored via the heparin assay / anti-factor Xa assay.
Unfractionated and LMW heparin can be reversed using protamine sulfate; fondaparinux has no antidote.

Question 10

What anti-coagulant is a vitamin K antagonist that inhibits vitamin K-dependent γ-carboxylation of factors II, VII, IX, X, Protein C and S (but does not affect already synthesized factors)?

Answer 10

Warfarin

Question 11

Traditionally, how are heparin and warfarin used together to prevent thromboembolism (give timings and routes of administration)?

Answer 11

Heparin is given immediately and parenterally, followed by warfarin given chronically and orally (because it has a longer half life of 36 hours)

Question 12

What is the half life of warfarin? How many days does it take for the long-term coagulation to start taking effect?

Answer 12

36 hours; 3-5 days

Question 13

How does increased vitamin K consumption, long term antibiotic therapy, and barbiturate induction of P450 affect warfarin’s activity?

Answer 13

Increased vitamin K and increased P450 metabolism decreases warfarin activity;
antibiotics decrease vitamin K which increases warfarin activity

Question 14

In addition to bleeding, what are 3 possible side effects of warfarin therapy?

Answer 14

Thrombosis during therapy onset (due to protein S and C decrease), skin necrosis, and teratogenicity

Question 15

Describe 4 methods of reversing warfarin therapy and how long each method takes.

Answer 15

1. Stop the drug (1-2 days)
2. Give vitamin K (10 hours)
3. Give fresh frozen plasma (immediate)
4. Give active factor concentrates like prothrombin complex and recombinant factor VII (immediate)

Question 16

List the 4 direct thrombin inhibitors. Do they inactivate fibrinogen-bound or unbound thrombin?

Answer 16

Lepirudin, bivalirudin, argatroban, dabigatran; they inactivate both bound and unbound thrombin

Question 17

Which of the direct thrombin inhibitors are competitive/reversible, and which are noncompetitive/irreversible?

Answer 17

According to our drug table, dabigatran is competitive/reversible while lepirudin and bivalirudin are noncompetitive/irreversible.

Question 18

Which 2 direct thrombin inhibitors are derived from the leech polypeptide hirudin?

Answer 18

Lepirudin and bivalirudin

Question 19

Which of the direct thrombin inhibitors are administered parenterally and monitored using PTT?

Answer 19

Lepirudin, bivalirudin, and argatroban

Question 20

Name the 2 direct Xa inhibitors. Are they competitive/reversible or noncompetitive/irreversible inhibitors?

Answer 20

Rivaroxaban and apixaban; competitive/reversible

Question 21

Compare the administration route and available antidotes for the direct Xa inhibitors vs. the direct thrombin inhibitors.

Answer 21

The Xa inhibitors are given orally while the thrombin inhibitors are given parenterally - except dabigatran is oral even though it’s a thrombin inhibitor.
There are no antidotes for any of the direct thrombin or direct Xa inhibitors!

Question 22

Warfarin and unfractionated heparin are similar in that they are both difficult to dose, but different in the methods used to monitor their effects. What monitoring method is used for each drug?

Answer 22

Warfarin is monitored via PT/INR; unfractionated heparin is monitored via PTT