Dear Editor

The article, “A Report of Outcomes After Orthotopic Liver Transplant With Allografts From Heparin Antibody-Positive Donors,” by Thomas Aloia and John Goss, was of interest to us, particularly the recommended argatroban dosing for organ procurement in patients with confirmed heparin-induced thrombocytopenia (HIT).¹ The article described 2 organ donors with confirmed HIT who received argatroban at 200 mg infused over 15 minutes. Both cases resulted in successful organ recovery and transplant to the recipients. We appreciate the efforts of the authors for this case report regarding the use of argatroban for organ procurement, which is not yet a well-established therapy in the literature. However, we would like to bring to light the possibility of a mathematical error in this article and the need to clarify the dose administered because this article could continue to be referenced. Caution is advised when differentiating between the reported dose given to patients and the dose recommended by the authors.

The recommended argatroban dose presented in the article by Aloia and Goss1 was intended to duplicate the manufacturer recommended argatroban bolus dose of 350 µ g/kg for percutaneous inter-ventions in patients with HIT.² The donors in the case reportedly weighed 60 kg and 65 kg, respectively, and both donors were reported to receive argatroban at 200 mg infused over 15 minutes.¹ Based on a dose of 350 µ g/kg, the patients should have received argatroban at 21 mg and 23 mg, respectively. However, this could be rounded to the nearest tens, which is 20 mg. Discussions with the author to clarify the dose were unsuccessful because of the length of time that has passed since the article was published in 2009.

We raise our concerns because we have noted that this article has been referenced and discussed in the article by Korte and colleagues³ (“Pharmacists’ guide to the management of organ donors after brain death”). In that clinical review, the authors described the successful use of argatroban at 200 mg for organ procurement, without further discussing the recommended argatroban dose of 350 µ g/kg based on percutaneous interventions. This review is likely to be used as guidance by pharmacists, and therefore a mathematical error could lead to coagulopathy-related complications in the transplant recipients.

An additional report supports the use of argatroban at a dose of 350 µ g/kg. Sharif and colleagues described successful organ recovery with argatroban for a HIT-positive recipient.⁴ The donor initially received heparin at 5000 U subcutaneously every 12 hours, which was discontinued the day of the operation for liver transplant to a HIT-positive recipient.⁴ The donor was reported to receive argatroban at 350 mcg/kg for a total of 26 mg.⁴

Organ procurement in the setting of HIT is extremely rare, and the literature is limited to case reports that predominantly recommend an argatroban dose of 350 µ g/kg. We believe the authors Aloia and Goss may have incorrectly converted micrograms to milligrams for the published article. Until further clarification in the available literature, we recommend no more than an initial dose of 350 µ g/kg for argatroban in the setting of an organ transplant recipient with HIT.

References:

1. Aloia TA, Goss JA. A report of outcomes after orthotopic liver transplant with allografts from heparin antibody-positive donors. Exp Clin Transplant. 2009;7(1):13-17.
   CrossRef - PubMed
   
2. Argatroban injection label. Package insert. Encysive Pharmaceuticals Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020883s014lbl.pdf
   CrossRef - PubMed
   
3. Korte C, Garber JL, Descourouez JL, Richards KR, Hardinger K. Pharmacists’ guide to the management of organ donors after brain death. Am J Health Syst Pharm. 2016;73(22):1829-1839. doi:10.2146/ajhp150956
   CrossRef - PubMed
   
4. Sharif L, Millis MA, Demarest CT, et al. Use of argatroban in donor lung procurement: a case report. Am J Case Rep. 2021;22:e934054. doi:10.12659/AJCR.934054
   CrossRef - PubMed