Canterbury DHB

Management of HIT

Bivalirudin therapy

• Bivalirudin is presented in vials containing 250 mg powder, for reconstitution and IV infusion, for HIT. Prescribers should be aware that there is no recombinant huriden licensed in New Zealand for HIT, and therefore Bivalirudin must be prescribed under section 29 of the Medicines Act, and verbal consent is needed from the patient to ensure they are aware of this.
• Treatment with Bivalirudin should be initiated under the guidance of a physician with experience in coagulation disorders.

Initial dosage

Anticoagulation in adult patients with HIT type II and thromboembolic disease:

• 0.75 mg/kg body weight intravenously as a bolus dose
• followed by 0.2 mg/kg body weight/hour as a continuous intravenous infusion for 2 - 10 days or longer if clinically needed.

Note: the bolus dose and infusion rate must be reduced in case of known or suspected renal insufficiency (creatinine clearance below 30 mL/min, see below).

Normally, the dosage depends on the patient's body weight. This is valid up to a body weight of 110 kg. In patients with a body weight exceeding 110 kg the dosage should not be increased beyond the 110 kg body weight dose.

Monitoring of the Bivalirudin dosage regimen - standard recommendations

• In general, the dosage (infusion rate) should be adjusted to the activated partial thromboplastin time, aPTT.
• The first aPTT determination should be done 4 hours after start of Bivalirudin therapy.
• The aPTT should be monitored at least once daily. More frequent determinations may be necessary, for example, in patients with renal impairment or with an increased risk of bleeding.
• Target range (therapeutic window) for the aPTT is 1.5 to 3 fold prolongation of the normal control value.

Dose modifications of the Bivalirudin dosage regimen

• Any aPTT value out of the target range is to be confirmed at once before drawing conclusions with respect to dose modifications, unless there is a clinical need to react immediately.
• If the confirmed aPTT value is above the target range, the infusion should be stopped for two hours. At restart, the infusion speed should be decreased by 50% (no additional intravenous bolus should be administered). The aPTT should be determined again 4 hours later.
• If the confirmed aPTT value is below the target range, the infusion speed should be increased by 20%. The aPTT should be determined again 4 hours later.

Recommendations for use in patients with renal impairment

• As Bivalirudin is almost exclusively excreted and metabolised renally, the patient's renal function should be considered before administration. In case of renal impairment, relative overdose might occur even under standard dosage regimen. Therefore, the bolus dose and infusion rate must be reduced in case of known or suspected renal insufficiency (creatinine clearance below 30 mL/min).
• In any case, the bolus dose must be reduced to 0.2 mg/kg body weight.
• The infusion rate must be reduced as follows. Additional aPTT monitoring is mandatory.

  Table 1: Reduction of infusion rate in patients with renal impairment
  Creatinine clearance [mL/min]	Creatinine value [mcmol/L]	Adjusted infusion rate [% of original dose]
  45 - 60	141 - 177	50%
  30 - 44	178 - 265	30%
  15 - 29	266 - 530	15%
  below 151	above 5301	avoid or STOP infusion!1

1. In haemodialysis patients or in case of acute renal failure (creatinine clearance below 15 mL/min or creatinine value above 530 mcmol/L), infusion of Bivalirudin is to be avoided or stopped.

   Only if aPTT values have fallen below the lower therapeutic limit (see Monitoring: target range), further intravenous bolus doses of 0.1 mg/kg body weight may be considered every other day.

Patients scheduled for a switch to oral anticoagulation

Recommendation:

• If a patient is scheduled to receive warfarin for oral anticoagulation after Bivalirudin therapy, the following should apply: Warfarin should be initiated only when platelet counts are normalising. The intended maintenance dose should be started with no loading dose. To avoid prothrombotic effects when initiating warfarin, continue parenteral anticoagulation for 4 to 5 days. The parenteral agent can be discontinued when the INR stabilises within the desired target range.

Topic Code: 5191