Evaluation of 2 Nomogram-Based Strategies for Dosing Argatroban in Patients With Known or Suspected Heparin-Induced Thrombocytopenia

Abstract

No study has compared 2 different dosing strategies for argatroban titration nor has any published nomogram demonstrated improvement in outcomes. This study was conducted to evaluate the effectiveness of 2 argatroban nomograms on reaching therapeutic anticoagulation. Patients treated with argatroban were separated into 2 sliding scale groups, percentage adjustments (PAs) and predefined dose increments (PDIs). The primary outcome was the time to reach a therapeutic activated partial thromboplastin time (aPTT). The average initial dose and dose to achieve a therapeutic aPTT were similar between the groups. There was also no difference in the number of dose changes. The time to reach a therapeutic aPTT was 2 hours shorter in the PDI compared to the PA group, 8 ± 4 hours versus 10 ± 4 hours, P = .015. This study demonstrates a significant time advantage associated with a PDI nomogram compared to a PA nomogram but no difference with respect to the number of rate changes.

Comparison of a predefined dose increment nomogram with a percentage adjustment nomogram in patients receiving argatroban therapy

“…The differences in the therapeutic aPTT ranges between the 2 nomograms used in our study may have contributed to an increased percentage of aPTT levels within the therapeutic range in the PA arm as the goal aPTT range was wider than that in the PDI arm. Arpino et al 10 found no difference between the PDI and PA arms with regard to the initial rate and rate of argatroban at therapeutic aPTT. In our study, there was a statistically significant difference in the initial rate of argatroban between the PDI and PA arms; however, there was no difference in the rate of argatroban at therapeutic aPTT between the 2 arms.…”

“…Arpino et al 10 assessed the time to reach therapeutic aPTT (50-70 seconds) and found that it took 2 hours less to reach therapeutic aPTT in the PDI arm than in the PA arm (8 ± 4 hours vs. 10 ± 4 hours; P ¼ 0.015). In our study, we found that the time to reach therapeutic aPTT was shorter by 2.5 hours in the PA arm than in the PDI arm; however, the results were not statistically significant.…”

“…9 The current evidence recommends starting argatroban therapy but does not provide guidance on how to titrate the medication to achieve a therapeutic aPTT. 2,5 Arpino et al 10 assessed the time to reach therapeutic aPTT using 2 different dose adjustment strategies: percentage adjustment (PA) and PDI. They found that the patients in the PDI arm took less time to reach therapeutic aPTT than the patients in the PA arm.…”

“…In addition, they found no difference in the number of dose changes needed to reach therapeutic aPTT. 10 Although there is well-established evidence of initiating argatroban therapy in patients with suspected HIT, there is no recommendation for titrating argatroban and no studies evaluating compliance with an institutional nomogram and its impact on achieving therapeutic aPTT while on argatroban. [9][10][11] Finally, there is no established calculation method for time in the therapeutic range for argatroban.…”

Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors

“…The time to reach a therapeutic aPTT was shorter by 2 hours in a nomogram based on predefined dosing increments (e.g., 0.2 µg/kg/min) compared with one based on percentages (8 AE 4 hours vs. 10 AE 4 hours, p ¼ 0.015). 28 Another group developed a nomogram for argatroban and bivalirudin, and compared it to historical control group, reporting that the nomogram shortened time to achieve target aPTT (target 50-80 seconds), decreased the number of titrations required to achieve aPTT goal, and improved the percentage of aPTT values in goal range. 29 Another study, involving patients on argatroban or bivalirudin, developed a nomogram and compared it to a pre-nomogram control group.…”