Anticoagulant Reversal Agents Flashcards
Plasma Derived Fibrinogen Concentrate
Riastap
Fibrinogen concentrate = factor I
No thawing or blood type matching required
Riastap Dose
900-1300mg per 50mL vial
Factor Complex Concentrates
Profilnine
K-centra
Factor Complex Concentrate
Clinical Indications
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)
3-Factor Concentrate
Profilnine
Factor IX complex
Complex concentrate contains factors II, IX, X, & low levels VII
NO heparin or preservatives
Profilnine Dose
10-15u/kg IBW
Max dose 1,000u
Profilnine Clinical Indications
Hempohilia B (factor IX deficiency) 1° reserved for cardiac cases NOT indicated to reverse Warfarin or factor Xa
4-Factor Concentrate
K-centra
Contains antithrombotic proteins C & S, heparin, & factors II, VII, IX, & X
First FDA approved 4-factor concentrate
Expensive $
K-Centra Dose
INR 2-4 25u/kg Max 2,500u
INR 4-6 35u/kg Max 3,500u
INR >6 50u/kg Max 5,000u
K-Centra Clinical Indications
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
Recombinant Activated Factor VII
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
NovoSeven Dose
Widely variable range 20-200mcg/kg Most common 90mcg/kg IV bolus Reconstitute w/ sterile H2O Re-dose Q2H \$\$$
NovoSeven Clinical Indications
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)
NovoSeven Considerations
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
Antifibrinolytics
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)
Aminocaproic Acid (Amicar)
Lysine analog
Inhibits proteolytic enzyme plasmin (responsible for fibrinolysis)
Aminocaproic Acid Dose
Bolus 5-15g followed by 1-2g/hr infusion
Pediatrics:
Bolus 75-150mg/kg
Infusion 5-30mg/kg/hr
Aminocaroic Acid
Clinical Indications
Acute bleeding d/t fibrinolytic activity
Trauma
Cardio-pulmonary bypass
Spinal fusions
Tranexamic Acid (TXA)
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
Tranexamic Acid PK/PD
8-10x more potent than Amicar
Elimination 1/2 life 2hr
Renal excretion
TXA Dose
10-15mg/kg IV up to 1g
Followed by 1-5mg/kg/hr infusion
TXA Clinical Indications
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
TXA Contraindications
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
Protamine
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
Protamine Dose
1-1.5mg per 100u heparin
Dependent on last ACT & estimated total IV heparin w/in last 2hr
Protamine Adverse Effects
Hypotension (rapid IV injection = histamine release) Pulmonary HTN Allergic reactions (pre-treat w/ histamine antagonist)
Protamine Allergy Risk
- Prior reaction to Protamine
- Allergy to vertebrae fish
- Exposure to NPH insulin
- Allergy to any drug
- Prior exposure to Protamine
D-amino-D-arginine Vasopressin (DDAVP)
Synthetic analogue natural hormone arginine vasopressin
Causes release endogenous stored factor VIII & von Willebrand
Improves platelet function
DDAVP PK/PD
Elim 1/2 time 3hr
Up to 9hr in severe renal impairment
Renal excretion
DDAVP Dose
0.3mcg/kg IV infusion over 15-30min to prevent hypotension
DDAVP Considerations
↑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
