Ch. 11 - Pharmacologic agents

Question 1

What pharmacologic agents may require reversal for hemostasis?

Answer 1

Warfarin
Heparin
Antiplatelet drugs
Direct thrombin inhibitors
Anti-Xa inhibitors

Question 2

Describe the mechanism of action of warfarin.

Answer 2

Racemic warfarin (of which the S-racemer is more potent) acts as a vitamin K antagonist to inhibit VKORC in the synthesis of factors II, VII, IX, and X (and protein S, C)

Question 3

How can a supratherapeutic INR with bleeding be reversed?

Answer 3

Stop warfarin!
Vitamin K (IV), FFP (multiple units), or PCC

Question 4

How is a very supratherapeutic INR (>9) without bleeding managed?

Answer 4

High dosage of vitamin K (5mg or more), possibly IV

Question 5

How is a somewhat supratherapeutic INR without bleeding managed?

Answer 5

Give vitamin K if INR >4 (oral, 1-5mg), or simply discontinue oral therapy.

Question 6

What are the advantages of prothrombin complex concentrates over FFP in reversing warfarin?

Answer 6

Smaller doses are needed, ABO blood typing is not required, and there is less risk of reaction.

Question 7

What are the different types of PCCs?

Answer 7

Three-factor PCCs (Profilnine, Bebulin)
Four-factor PCCs (K-centra) *better
Activated PCC (FEIBA?)

Question 8

What is the indication for activated prothrombin complex concentrates?

Answer 8

Hemophilia–not reversal of warfarin.

Question 9

How are PCC products prepared?

Answer 9

Solvent detergent treatment of human plasma with fractionation.

Question 10

What are the indications for K-centra?

Answer 10

Reversal of warfarin coagulopathy (FDA-approved)

Coagulopathy due to other oral anticoagulants

Question 11

How is K-centra dosed?

Answer 11

If INR 2-4: 25u/kg
If INR 4-6: 35u/kg
If INR >6: 50u/kg
(assign a max weight of 100kg)

Question 12

What should follow after K-centra administration?

Answer 12

Re-check PT/PTT 2hrs later. Add vitamin K 10-12hrs later when K-centra effect is weaning off.

Question 13

What are some contraindications for K-centra?

Answer 13

Thrombotic conditions (DIC, APS, Protein C/S/AT deficiency)
Pregnancy
Recent history of DVT/PE/MI/TIA

Question 14

How is heparin produced, and how does it exert anticoagulant effect?

Answer 14

Heparin is isolated from bovine or porcine sources. Heparin binds to antithrombin III, greatly potentiating its effect.

Question 15

How is LMWH produced, and how does it compare to UFH?

Answer 15

Heparin is depolymerized or digested to yield smallermolecules which have more predictable dose reponse.

Question 16

How is heparin eliminated? How should it be monitored?

Answer 16

80% via renal route.

Measure PTT for UFH, Anti-Xa activity for LMWH.

Question 17

How is protamine produced? What is its indication?

Answer 17

Derived from salmon sperm/gonad, it is a highly basic/cationic polypeptide which is used as a heparin antidote.

Question 18

In general, how is protamine dosed?

Answer 18

1mg protamine neutralizes 100U of heparin. IT can also neutralize 1mg of enoxaparin,or 100u of dalteparin.

Question 19

What is the heparin rebound phenomenon, and why is it significant?

Answer 19

Hypocoagulability which resurfaces following heparin neutralization with protamine. It is a concern in the early post-op period after cardiac surgery and it cannot be detected by ACT.

Question 20

How can residual heparin effect be monitored following neutralization with protamine?

Answer 20

TEG (thromboelastography) with or without heparinase (compare R-times)

Review DIC panel (look for prolonged PTT and TT, but rule out hypofibrinogenemia first)

Question 21

What is NovoSeven, and what is its use?

Answer 21

Recombinant factor VIIa (expressed from cultured hamster kidney cells), which is approved for prevention or treatment of bleeding in patients with hemophilia and antibodies. However, it is almost always used off-label for other bleeders.

Question 22

What is the mechanism of action of desmopressin and what is it used for?

Answer 22

It increases plasma levels of fVIII and vWF probably by release from vascular endothelium. Used for von Willebrand disease, uremic thrombocytopathy, and other bleeding conditions.

Question 23

When should RhoGAM be given?

Answer 23

At 28wks of pregnancy, within 72hrs of childbirth, and anytime fetomaternal hemorrhage is suspected.

Question 24

What are three indications for RhIG treatment?

Answer 24

Prevention of HDFN
Prevention of D-sensitization in mismatch
ITP

Question 25

What is aprotinin?

Answer 25

A serine protease inhibitor which acts as a fibrinolytic agent but is too toxic for most clinical use.

Question 26

When are antifibrinolytic agents used?

Answer 26

In situations of primary fibrinolysis (not in secondary cases such as in DIC).

Question 27

What are the indications for aminocaproic acid? How is it dosed?

Answer 27

For fibrinolytic bleeding (eg following tPA). Dose 5gm first, then 1gm per hour until bleeding stops (up to 8hrs).

Question 28

How is aminocaproic acid eliminated? What is its half life? Should it be used in neonates?

Answer 28

65% renally excreted, with a half-life of 2hrs. It should not be given to neonates as it contains benzyl alcohol (associated with fatal “gasping syndrome”).

Question 29

What is the approved indication for tranexamic acid?

Answer 29

To reduce or prevent bleeding during tooth extraction in patients with hemophilia. It is also helpful for reducing instrumented bleeding, post-delivery hemorrhage.

Question 30

How is tranexamic acid dosed? Describe its kinetics.

Answer 30

10mg/kg IV given 2-3 times per day. It is renally excreted with a half-life of 2hrs.