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Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia in Elderly Patients

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Abstract

Background

Argatroban, a direct thrombin inhibitor that has reduced clearance in elderly versus younger volunteers, is used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT).

Objective

To evaluate the effect of aging on argatroban therapy, including dosage, anticoagulant responses, clinical outcomes and factors influencing those responses, in elderly patients with HIT or a history of HIT.

Methods

This was a retrospective multicentre database analysis of 118 inpatients treated with argatroban at six medical centres between August 2001 and January 2005. Sixty-two adults aged ≥;65 years were administered argatroban for clinically diagnosed HIT (n = 54) or a history of HIT (n = 8). Argatroban infusion was adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5–3 times baseline. All study measures and analyses were prospectively defined. Argatroban dosage patterns, aPTTs and platelet count responses, and 37-day outcomes (death, amputation, new thrombosis, major bleeding) were summarised for patients stratified by age (65–74 years [n = 31]; 75–84 years [n = 26]; ≥85 years [n = 5]) to identify possible age-related trends. Regression analyses explored relationships between dose and patient age, liver function and renal function. Cox proportional hazards models evaluated the effect of age, dose, gender, aPTT and platelet count on the risk of new thrombosis.

Results

In each age group, the median argatroban dosage was initially 1.0 µg/kg/min and was generally maintained at or near that dose during therapy (median, 5–7 days). Therapeutic aPTTs occurred within 11.5 hours; the median aPTT during therapy was 54.7 seconds, without obvious trend by age. By regression analysis, the initial and mean argatroban dosages decreased 0.08–0.09 µg/kg/min with each 0.2 mg/dL increase in serum creatinine, but no association was detected between dose and patient age, serum total bilirubin, calculated creatinine clearance or blood urea nitrogen. Platelet counts recovered within 6–7 days of initiating therapy, without apparent trend by age. No patient experienced amputation or major bleeding, and no patient in the oldest group died or had new thrombosis. Overall, 13 (21%) patients died (9 in the 65–74 years group; 1 receiving argatroban) and 5 (8%) had new thrombosis (4 in the 65–74 years group; 2 receiving argatroban), comparing favourably with previously reported rates, irrespective of patient age. By univariate (but not multivariate) analysis, the risk of new thrombosis decreased with increasing argatroban dose (hazard ratio 0.020; 95% CI 0.001, 0.757; p = 0.035). No effect of age or the other covariates considered on thrombotic risk was detected.

Conclusion

Argatroban at a median initial dosage of 1.0 µg/kg/min, adjusted to achieve median aPTTs of 54.7 seconds during therapy, generally provided safe, adequate anticoagulation across a wide age range in elderly patients with HIT or a history of HIT. In these elderly patients, age was not a significant determinant of argatroban dosage or thrombotic risk. Prospective evaluation of this initial dose of argatroban in the elderly is warranted.

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Acknowledgements

This study was supported by GlaxoSmithKline (GSK). GSK personnel offered critical comment on the statistical analysis plan and draft manuscript. The acceptance or rejection of the suggestions was fully at the authors’ discretion, as was the decision to submit the manuscript for publication.

Dr Bartholomew has been a speaker for GSK. Dr Hursting has received consultancy fees from GSK. Dr Pietrangeli has no conflicts of interest that are directly relevant to the content of this study.

The authors express their gratitude to David A. McCollum, MS, for his assistance with the statistical analysis, Eliezer Katz, MD, FACS, for his critical comments and Jenna Tincher-Mann, BA, for her editorial assistance.

Author information

Authors and Affiliations

  1. The Cleveland Clinic, Cleveland, Ohio, USA

    John R. Bartholomew

  2. CTI Clinical Trial and Consulting Services, Cincinnati, Ohio, USA

    Carolynn E. Pietrangeli

  3. Clinical Science Consulting, Austin, Texas, USA

    Marcie J. Hursting

Authors
  1. John R. Bartholomew
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  2. Carolynn E. Pietrangeli
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  3. Marcie J. Hursting
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Correspondence to John R. Bartholomew.

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Bartholomew, J.R., Pietrangeli, C.E. & Hursting, M.J. Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia in Elderly Patients. Drugs Aging 24, 489–499 (2007). https://doi.org/10.2165/00002512-200724060-00005

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