Anticoagulant Reversal Agents

Question 1

Plasma Derived Fibrinogen Concentrate

Answer 1

Riastap
Fibrinogen concentrate = factor I
No thawing or blood type matching required

Question 2

Riastap Dose

Answer 2

900-1300mg per 50mL vial

Question 3

Factor Complex Concentrates

Answer 3

Profilnine

K-centra

Question 4

Factor Complex Concentrate

Clinical Indications

Answer 4

Reverse significant vitamin K antagonism effects
Emergent or urgent surgery
Clotting deficiencies

• Provide faster coagulopathy correction (30min)
• Plasma factors are dilute & require 10-15mL/kg to reverse oral anticoagulants
• ↓infection risk or transfusion reaction d/t processed & washed
• Action dependent on adequate platelet & fibrinogen (+coagulation factors)

Question 5

3-Factor Concentrate

Answer 5

Profilnine
Factor IX complex
Complex concentrate contains factors II, IX, X, & low levels VII
NO heparin or preservatives

Question 6

Profilnine Dose

Answer 6

10-15u/kg IBW

Max dose 1,000u

Question 7

Profilnine Clinical Indications

Answer 7

Hempohilia B (factor IX deficiency)
1° reserved for cardiac cases
NOT indicated to reverse Warfarin or factor Xa

Question 8

4-Factor Concentrate

Answer 8

K-centra
Contains antithrombotic proteins C & S, heparin, & factors II, VII, IX, & X
First FDA approved 4-factor concentrate
Expensive $

Question 9

K-Centra Dose

Answer 9

INR 2-4 25u/kg Max 2,500u
INR 4-6 35u/kg Max 3,500u
INR >6 50u/kg Max 5,000u

Question 10

K-Centra Clinical Indications

Answer 10

Reverse vitamin K antagonists w/ INR >1.5

Potential to reverse factor Xa inhibitors (Xarelto & Eliquis) at higher doses 50u/kg vs. 20-30u/kg

Question 11

Recombinant Activated Factor VII

Answer 11

NovoSeven (rFVIIa)
Activated form factor VII causes coagulation w/o requiring factors VIII & IX
Promotes hemostasis vs. extrinsic coagulation cascade pathway activation
Forms complex w/o tissue factor (III)
Elim 1/2 time 2-2.5hr

Question 12

NovoSeven Dose

Answer 12

Widely variable range 20-200mcg/kg
Most common 90mcg/kg IV bolus
Reconstitute w/ sterile H2O 
Re-dose Q2H
\$\$$

Question 13

NovoSeven Clinical Indications

Answer 13

Hemophilia A deficiency
Hemophilia B deficiency
Congenital factor VII deficiency
Off-label to prevent & treat coagulopathy & major blood loss (PPH, trauma, various anticoagulant reversal, high-risk cardiothoracic, spinal, transplant, or vascular surgery)

Question 14

NovoSeven Considerations

Answer 14

Risk adverse thrombotic events → DIC, advanced atherosclerotic disease, crush injury, septicemia, concomitant prothrombin complex concentrates
Does not stop surgical hemorrhage
↓blood transfusion requirements in hemorrhage shock patients from blunt trauma
Addition NOT replacement → admin w/ other blood products (adequate FFP, cryoprecipitate, & platelets required to achieve full effect)
MOA depends on platelet & fibrinogen function
Potential ↑thrombus risk particularly in patients w/ hemophilia

Question 15

Antifibrinolytics

Answer 15

Prevent fibrin lysis → promote clot formation
Used to treat & prevent excessive bleeding as fibrinolysis inhibitors
Interfere w/ fibrinolytic enzyme plasmin formation

Lysine analogues
Serine protease inhibitors (Aprotinin no longer available d/t adverse effects)

Question 16

Aminocaproic Acid (Amicar)

Answer 16

Lysine analog

Inhibits proteolytic enzyme plasmin (responsible for fibrinolysis)

Question 17

Aminocaproic Acid Dose

Answer 17

Bolus 5-15g followed by 1-2g/hr infusion

Pediatrics:
Bolus 75-150mg/kg
Infusion 5-30mg/kg/hr

Question 18

Aminocaroic Acid

Clinical Indications

Answer 18

Acute bleeding d/t fibrinolytic activity
Trauma
Cardio-pulmonary bypass
Spinal fusions

Question 19

Tranexamic Acid (TXA)

Answer 19

Lysine analog
Cyklokapron or Lysteda
Amino acid lysine synthetic analogue
Inhibits fibrinolysis via competitively binding to lysine receptor sites on plasminogen → prevents plasmin from binding to & degrading fibrin
Preserves the fibrin matrix structure ↓bleeding rate

Question 20

Tranexamic Acid PK/PD

Answer 20

8-10x more potent than Amicar
Elimination 1/2 life 2hr
Renal excretion

Question 21

TXA Dose

Answer 21

10-15mg/kg IV up to 1g

Followed by 1-5mg/kg/hr infusion

Question 22

TXA Clinical Indications

Answer 22

GI bleeding
Surgical bleeding
Non-cerebral trauma (only beneficial w/in 1st 3hr)
Pediatric spinal fusions or craniosynostosis
Ortho procedures (common w/ joints)
Cardiac procedures w/ or w/o CPB
OB massive transfusion protocols

Question 23

TXA Contraindications

Answer 23

Active intravascular bleeding
Anaphylaxis
Subarachnoid hemorrhage

Precautions:

• Impaired renal function ↓dose
• UTI → ureteral obstruction
• Hypotension w/ rapid IV injection
• Color vision defect
• Seizure disorders
• Concomitant admin w/ factor concentrates → clotting

Question 24

Protamine

Answer 24

Simple proteins obtained from salmon sperm
Positively charged alkaline protamine combines w/ negatively charged acidic heparin to form stable complex w/o anticoagulant activity
Protamine-heparin complex removed by reticuloendothelial system

Question 25

Protamine Dose

Answer 25

1-1.5mg per 100u heparin | Dependent on last ACT & estimated total IV heparin w/in last 2hr

Question 26

Protamine Adverse Effects

Answer 26

``` Hypotension (rapid IV injection = histamine release) Pulmonary HTN Allergic reactions (pre-treat w/ histamine antagonist) ```

Question 27

Protamine Allergy Risk

Answer 27

1. Prior reaction to Protamine 2. Allergy to vertebrae fish 3. Exposure to NPH insulin 4. Allergy to any drug 5. Prior exposure to Protamine

Question 28

D-amino-D-arginine Vasopressin (DDAVP)

Answer 28

Synthetic analogue natural hormone arginine vasopressin Causes release endogenous stored factor VIII & von Willebrand Improves platelet function

Question 29

DDAVP PK/PD

Answer 29

Elim 1/2 time 3hr Up to 9hr in severe renal impairment Renal excretion

Question 30

DDAVP Dose

Answer 30

0.3mcg/kg IV infusion over 15-30min to prevent hypotension

Question 31

DDAVP Considerations

Answer 31

↑platelet adhesion w/in 30min More potent than natural arginine vasopressin to ↑plasma levels factor VIII activity in patients w/ von Willebrand's disease Hypotension - most commonly reported SE Contraindications include hypersensitivity, moderate to severe renal impairment, & hyponatremia