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Evaluation of direct thrombin inhibitors during a critical heparin shortage

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Abstract

A recent heparin shortage related to an outbreak of African Swine Flu in China led to substantial increase in the use of direct thrombin inhibitors (DTI) as an alternative. We evaluated the safety and efficacy of DTIs by assessing the anticoagulation assays within the initial 48 h of therapy comparing before and during shortage. A retrospective evaluation of bivalirudin and argatroban was conducted at a single center before (May 24, 2018 through August 25, 2019) and during heparin shortage (August 26, 2019 through February 20, 2020). The primary outcome was time to first therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included the percentage of time in therapeutic aPTT range, in-hospital mortality, incidence of recurrent thrombosis, and hemorrhagic events. Of the 204 patients included in the study, 95 patients [bivalirudin (n = 35), argatroban (n = 60)] were included in the pre-shortage cohort and 109 patients [bivalirudin (n = 68), argatroban (n = 41)] were during shortage. No significant difference was observed in the time to first therapeutic aPTT pre- and during shortage (8.9 h ± 10.8 vs 8.8 h ± 10.2, P = 0.62). Compared to pre-shortage cohort, a greater percentage of time was spent in therapeutic aPTT range within the initial 48 h (32% (0–50) vs. 41.6% (0–63), P = 0.04) during shortage without statistically significant differences in the rates of in-hospital mortality, thrombosis, or bleeding. While the optimal DTI protocol is still be determined, the protocols presented in this study allowed for wide-spread utilization of DTIs during a critical heparin shortage without compromising patient safety and effectiveness, likely reflective of the enhancement of DTI protocols, clinician education, and multidisciplinary collaboration and guidance from pharmacy and hematology.

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Authors and Affiliations

  1. Department of Pharmacy, Massachusetts General Hospital, 55 Fruit St. GRB005, Boston, MA, 02114, USA

    Christine S. Ji, Russel J. Roberts & Megan E. Barra

  2. Department of Medicine, Division of Biostatistics, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    Hang Lee

  3. Department of Medicine, Division of Hematology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    Rachel P. Rosovsky

Authors
  1. Christine S. Ji
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  2. Russel J. Roberts
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  3. Megan E. Barra
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  4. Hang Lee
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  5. Rachel P. Rosovsky
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Contributions

CSJ and RPR contributed to data collection and critical writing or revising the intellectual content. CSJ, RJR, MEB, HL and RPR contributed significantly to concept and design, analysis, and interpretation of data. All authors reviewed and approved this manuscript.

Corresponding author

Correspondence to Christine S. Ji.

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Conflict of interest

CSJ, RJR, MEB, and HL have no conflicts of interest to declare. RPR received institutional grant from Bristol‐Myers Squibb (BMS) and honoraria for advisory boards from Janssen Pharmaceuticals, Bristol‐Myers Squibb, Dova Pharmaceutical, and Portola, all outside the scope of submitted work.

Disclaimer

These dosing protocols were created by clinical experts for use in inpatients at Massachusetts General Hospital. These algorithms should not replace clinical judgment incorporating patient‐specific factors or institutional, national, or international guidelines or practice

Ethical approval

Rachel P. Rosovsky: institutional grant from Bristol‐Myers Squibb (BMS) and honoraria for advisory boards from Janssen Pharmaceuticals, Bristol‐Myers Squibb, Dova Pharmaceutical, and Portola, all of which are outside the scope of submitted work.

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Ji, C.S., Roberts, R.J., Barra, M.E. et al. Evaluation of direct thrombin inhibitors during a critical heparin shortage. J Thromb Thrombolysis 52, 662–673 (2021). https://doi.org/10.1007/s11239-020-02357-4

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  • DOI: https://doi.org/10.1007/s11239-020-02357-4

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