Mechanism of Action
- Local fibrinolysis by binding to fibrin, converts entrapped plasminogen to plasmin
Pharmacokinetics
- Half-Life: ~45 min.
- Metabolism: Mainly liver
- Onset of action: Immediate-30 min.
- Steady state reached: 1 to 3 hours
- Protein/albumin binding?: Yes
Dosing – Pediatric
- Heparin-induced thrombocytopenia
Initiating Therapy
- Prior to initiation of therapy, but no longer than 48 hours before, the following laboratory values are checked: CBC, coagulation panel (PT, PTT, fibrinogen activity), creatine, hepatic function panel, pregnancy test for females if applicable
- Argatroban should be ordered using dosing weight regardless of BMI. Dosing has been studied in patients up to 140 kg. If weight > 140kg, there is no contraindication; however, closer monitoring and clinical judgment is recommended.
- A brain ultrasound is suggested for patients less than 1 year old. If possible to be completed, a brain ultrasound is STRONGLY recommended for neonates less than 44 weeks corrected gestational age.
- When possible, patients should have a dedicated IV line for argatroban. The argatroban infusion must not be stopped or interrupted for other medications except in cases of emergency.
- No dose adjustment is required in patients with renal impairment
Initial Argatroban Infusion Rates
Start – 0.75 mcg/kg/min (consider maximum infusion rate of 10 mcg/kg/min)
- In patient with usual bleeding risk
- Without multiorgan organ failure and
- Normal hepatic function
Start – 0.2 mcg/kg/min (or alternatively consider use of bivalirudin)
- If bleeding patient or coagulopathy
- Hepatic impairment
- Multiorgan failure
- Cardiopulmonary bypass
Monitoring Therapy
- aPTT levels are used to monitor argatroban activity at PMCH.
- Ensure age-based aPTT values for preterm infants and term infants are used.
- aPTT Monitoring
- When initiating therapy, check the aPTT level 2 hours after the initiation of the argatroban infusion
- Additional aPTT level monitoring are checked 2-4 hours after each dose change until the patient has reached their targeted anticoagulation level.
- When 2 consecutive aPTT results obtained 4 hours apart are therapeutic, obtain aPTT level every 12 hours at a minimum.
- Ongoing monitoring
- HIT patient: daily platelet count until normal and then twice weekly while on argatroban
- Check PT/INR at least twice weekly while on argatroban. Argatroban will significantly elevate PT/INR values. It is not recommended to give products for the sole purpose of correcting INR/fibrinogen unless clinically indicated.
- Check TEG as needed.
- Check fibrinogen at least twice weekly while on argatroban
Safety Precautions
- Renal Impairment: Dose adjustment recommended
- Hepatic Impairment: See dose adjustments above
aPTT Considerations
aPTT may not always be representative of argatroban concentration.
Can see Increased PTT with:
- Heparin contamination (from line)
- Kathy in special coag lab can run hepzyme assay. But for more rapid TAT, can get PT/INR or anti-Xa to identify contamination, since PT/INR won’t increase with heparin contamination alone, but will increase with bival concentration
- Traumatic phlebotomy –
- Low fibrinogen, low Factor XII or VIII (> 30-40% depletion)
- Hemolysis – with elevated plasma free hemoglobin
- Impaired renal function with resultant increased argatroban concentration
- Lupus anticoagulant
- Vitamin K deficiency
- Disseminated intravascular coagulopathy or other coagulopathy
- Hyperbilirubinemia
Can see Decreased PTT with:
- High factor VIII
- Systemic Inflammation
- Activation of the contact pathway
- Elevated fibrinogen or D-dimer
- Hypertriglyceridemia
- Hemolysis- elevated plasma free hemoglobin
- Delay in sample analysis
Background
Specific and reversible DTI irrespective of antithrombin. Binds to thrombin active site (unlike bivalirudin which binds both circulating and clot-bound thrombin via catalytic and anionic exosite)
Usual Reference Range for Therapeutic Dosin
- In patients with liver dysfunction adjust in increments of ≤0.05 mcg/kg/minute
- aPTT: Goal is 1.5-3x baseline (not to exceed 100 seconds)
- For aPTT <1.2x baseline, increase rate by 40%
- For aPTT 1.2-1.5x baseline, increase rate by 20%
- For aPTT 1.5-3x baseline, no change
- For aPTT >3-4x baseline (less than 100 seconds), decrease rate by 20%
- For aPTT >4x baseline, hold infusion for 1 hour, then recheck aPTT; decrease rate by 50% once aPTT <100 seconds
