We thank Ostendorf as well as Leidel and Kanz for their interest in our published article (1). Ostendorf addresses one of the main problems in dealing with the new direct oral anticoagulants (DOACs), and in this context he makes a good suggestion. The number of anticoagulants for clinical and outpatient use has increased enormously over the years, and this situation really triggers a desire for more practicable laboratory monitoring, with comparable results and units. Even though a treatment center may usefully restrict the number of anticoagulants to merely a few, in the emergency setting—with potentially resulting interventional or surgical healthcare provision strategies—the confrontation with any number of these substances cannot be ruled out. This problem has, however, remained unresolved for decades in the diagnostic evaluation of coagulation physiology that is used to monitor anticoagulation. Partial thromboplastin time (PTT) reagents are known to react differently to the same amount of unfractionated heparin. The multitude of anticoagulants has been continually increasing since the introduction of low molecular weight heparins and DOACs. A consensus about comparable inhibition units for factor Xa or thrombin has never been reached. What is needed is a consensus between treating physicians, manufacturers, and regulatory bodies. Ostendorf rightly asks for communication on generally calibrated inhibitor units; which is pragmatic and practical, and on the other hand a clear step ahead for emergency treatment. Such a consensus is, however, not in sight. Whether such universal units can then be scientifically ensured is currently not clear. For this reason, what is required in addition to a rough estimate by using global tests is the substance specific calibration for the individual DOACs, including measuring the individual plasma concentration.
We thank Leidel and Kanz for their valuable contribution in pointing out the recently published, evidence-based guideline from the US Neurocritical Care Society and the US Society of Critical Care Medicine (2). This refers to the reversal of antithrombotic agents exclusively in intracranial hemorrhages, which was not dealt with in detail because of the review character of our article. In addition to DOACs, the guideline also includes all other classes of substances and is therefore very well worth reading. The publication of the initial phase IV studies of the factor Xa inhibitor andexanet, which was cited by our colleagues, was not yet available to us at the time of writing our article. Further studies of antidote development, including specific substances vis-à-vis DOACs are likely to be published in the near future.
On behalf of the authors
Prof. Dr. med. Marc Maegele
Kliniken der Stadt Köln-Merheim
Universität Witten/Herdecke (Campus Köln-Merheim)
Conflict of interest statement
Prof. Maegele has received consultancy fees from TEM International, CSL Behring, Bayer, and LFB France and reimbursement of costs for congress attendance, travel, and accommodation from TEM International, CSL Behring, Bayer, and LFB France. He has received payment for giving a presentation at scientific meetings and funding for a research project of his own initiation from LFB France and CSL Behring.
|1.||Maegele M, Grottke O, Schöchl H, Sakowitz O, Spannagl M, Koscielny J: Direct oral anticoagulants in emergency trauma admissions—perioperative management, and handling hemorrhage. Dtsch Arztebl Int 2016; 113: 575–82 VOLLTEXT|
|2.||Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al.: Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016; 24: 6–46. CrossRef MEDLINE|