Reversal and Antidotes (not done)

When should anticoagulation be reversed?

When a patient has life-threatening bleeding or requires surgery requiring reversal

What are the drug-specific antidotes for UFH/LMWH, warfarin, and dabigatran?

UFH/LMWH: protamine; warfarin: vitamin K (phytonadione); dabigatran: idarucizumab

What happened to andexanet alfa (Andexxa), the former antidote for apixaban and rivaroxaban?

It was removed from the market in December 2025 due to safety concerns involving thrombosis and thrombosis-related death

What are PCCs primarily indicated for?

Urgent reversal of warfarin

How may PCCs be used for factor Xa inhibitor reversal?

Off-label

If PCC is used to reverse a factor Xa inhibitor, should PT, PTT, or anti-Xa levels be used to assess reversal?

No; coagulation testing to assess reversal is not useful and is not recommended

What anticoagulants does protamine reverse?

UFH and LMWH

What is the protamine dose for IV UFH reversal?

1 mg protamine reverses approximately 100 units of heparin

How much recent UFH exposure should be considered when calculating a protamine reversal dose?

The amount of heparin given during the previous 2–2.5 hours

Why is only the previous 2–2.5 hours of UFH considered for protamine dosing?

UFH has a very short half-life

What is the maximum protamine dose?

50 mg

What is the protamine dose if enoxaparin was given within the previous 8 hours?

1 mg protamine per 1 mg enoxaparin

What is the protamine dose if enoxaparin was given >8 hours ago?

0.5 mg protamine per 1 mg enoxaparin

What is the protamine dose for dalteparin reversal?

1 mg protamine per 100 anti-Xa units of dalteparin

Does protamine completely reverse LMWH?

No; it neutralizes a maximum of approximately 60–75%

What is the boxed warning for protamine?

Severe hypersensitivity reactions including hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, and pulmonary vasoconstriction

What are important adverse effects of protamine?

Hypotension, bradycardia, flushing, and anaphylaxis

What should be monitored during protamine administration?

aPTT or anti-Xa levels plus cardiac monitoring (ECG, BP, HR)

Why should protamine not be administered by rapid IV infusion?

Rapid infusion can cause hypotension

How should protamine be administered IV?

Slow IV push; maximum rate 50 mg over 10 minutes

What is the specific antidote for dabigatran?

Idarucizumab (Praxbind)

What is the idarucizumab dose for dabigatran reversal?

5 g IV given as two separate 2.5-g doses no more than 15 minutes apart

What important warning is associated with idarucizumab?

Thromboembolic risk and risk of serious adverse reactions due to the sorbitol excipient

What are important adverse effects of idarucizumab?

Headache, constipation, and hypersensitivity reactions

What medication name should idarucizumab (Praxbind) not be confused with?

Idarubicin

What is the antidote used for warfarin reversal?

Vitamin K (phytonadione; Mephyton)

What is the overall vitamin K dose range for warfarin reversal?

1–10 mg PO or IV depending on the clinical situation

How should IV vitamin K be administered to decrease the risk of anaphylaxis?

Dilute in at least 50 mL of compatible solution and infuse over at least 20 minutes; rate ≤1 mg/min

What boxed warning is associated with parenteral vitamin K?

Severe hypersensitivity reactions, including anaphylaxis, may occur during or immediately after IV or IM administration

What are important adverse effects of vitamin K?

Anaphylaxis, flushing, rash, and dizziness

What special handling is required for vitamin K during administration?

Protect from light

Why is SC vitamin K not recommended?

Variable absorption

Why is IM vitamin K not recommended?

Risk of hematoma

Which medications can decrease absorption of oral vitamin K?

Orlistat and mineral oil

Which clotting factors are contained in four-factor PCC?

Factors II, VII, IX, and X

Which natural anticoagulant proteins are contained in four-factor PCC?

Proteins C and S

What are examples of four-factor PCC products?

Kcentra and Balfaxar

How is four-factor PCC dosed?

IV dose is based on factor IX units/kg using body weight and the patient's INR

Should a four-factor PCC dose be repeated?

No

What boxed warning is associated with four-factor PCC?

Arterial and venous thromboembolic complications

What important contraindication applies to four-factor PCC in a patient with HIT?

Known HIT because four-factor PCC contains heparin

What product-specific contraindication applies to Kcentra?

Disseminated intravascular coagulation (DIC)

What product-specific contraindication applies to Balfaxar?

IgA deficiency with antibodies to IgA

What infectious risk is associated with four-factor PCC?

It is made from human blood and may transmit infectious agents

What are important adverse effects of four-factor PCC?

Headache, nausea/vomiting/diarrhea, asthenia, hypotension, hypokalemia, and thrombotic events

What should be administered with four-factor PCC for warfarin reversal?

Vitamin K

Why should blood not be allowed to back up into the IV line during four-factor PCC administration?

The product can clot in the line

What should be done with refrigerated four-factor PCC before administration?

Allow it to reach room temperature

Why should the actual potency on each four-factor PCC vial be checked?

Each vial can have a different potency of coagulation factors

Which factors are contained in three-factor PCC?

Factors II, IX, and X with low or nontherapeutic levels of factor VII

What is an example of a three-factor PCC product?

Profilnine

Is three-factor PCC use for anticoagulant reversal on- or off-label in these notes?

Off-label

How is three-factor PCC dosed?

Based on patient weight and INR

How should three-factor PCC be administered?

Slow IV infusion

What should be given with three-factor PCC?

Fresh frozen plasma (FFP) or factor VIIa, plus vitamin K

What is the major difference between three-factor and four-factor PCC?

Three-factor PCC has low/nontherapeutic factor VII; four-factor PCC contains therapeutic factor VII

What infectious risk is associated with three-factor PCC?

It is made from human blood and may transmit infectious agents such as viruses

What are important adverse effects of three-factor PCC?

Chills, fever, flushing, nausea, headache, and thrombosis

What can be given with three-factor PCC to minimize infusion-related adverse effects?

An antihistamine

What is the dose of recombinant factor VIIa (NovoSeven RT, Sevenfact) for reversal in these notes?

10–20 mcg/kg IV bolus over 5 minutes

Is recombinant factor VIIa use for anticoagulant reversal on- or off-label in these notes?

Off-label

What is the boxed warning for recombinant factor VIIa?

Serious thrombotic events