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• Re: Lumbar puncture on Direct Oral Anticoagulants (DOACs): a novel, emerging perspective
  Katherine Dodd, Hedley Emsley, Michael Desborough and Suresh Chhetri
  Published on: 12 October 2018
• Lumbar puncture on Direct Oral Anticoagulants (DOACs): a novel, emerging perspective
  Eugenia Rota, Sergio Agosti, Roberta Risso and Nicola Morelli
  Published on: 1 October 2018

• Published on: 12 October 2018

  Re: Lumbar puncture on Direct Oral Anticoagulants (DOACs): a novel, emerging perspective

  • Katherine Dodd, Neurology Registrar Salford Royal NHS Foundation Trust
  • Other Contributors:
    • Hedley Emsley, MD
    • Michael Desborough, MD
    • Suresh Chhetri, MD

  We are very grateful to Dr Rota and colleagues for their interest in our guideline.

  In essence, we agree that international consensus on DOAC level measurement and cut-off levels would be welcome.

  The experience reported by Dr Rota and colleagues of their use of idarucizumab for emergency reversal of dabigatran prior to lumbar puncture is reassuring. Our guideline refers to the need to consult a haematologist prior to administration; however, a guideline is for guidance and we recognise that locally agreed protocols may vary. Likewise, the timings mentioned in the guideline relating to the safe reinitiation of DOACs are by necessity pragmatic. Further evidence in this area will of course be very welcome to further inform practice.

  Conflict of Interest:
  None declared.

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• Published on: 1 October 2018

  Lumbar puncture on Direct Oral Anticoagulants (DOACs): a novel, emerging perspective

  • Eugenia Rota, Neurologist, Chief of the Neurology Unit San Giacomo Hospital, Novi Ligure, AL, Italy
  • Other Contributors:
    • Sergio Agosti, Cardiologist
    • Roberta Risso, Internal Medicine
    • Nicola Morelli, Neurologist, Radiologist

  Dear Editor,
  We read the article by Dodd et al. (2018) [1] with great interest. The authors provide evidence-based recommendations for the periprocedural management of antithrombotic and anticoagulant treatment in patients who require a lumbar puncture (LP). Indeed, this is a very relevant practical point for neurologists, above all when an urgent diagnostic LP is mandatory to rule out an infectious disease of the central nervous system, or a subarachnoid hemorrhage. The recommendations on adjustment/reversal of warfarin for patients on oral anticoagulants, who require LP, are well known, i.e. long-term LP allowed if INR is < 1.4. Whilst the question of how to manage patients on Direct Oral Anticoagulants (DOACS), a relatively novel pharmacological class, is also to be answered. Dodd et al’s article [1] reports that if a non-urgent LP has to be carried out he these patients, current recommendations vary among different advisory bodies about the time lapse necessary for DOAC withdrawal before the LP, depending on the renal function. The interesting possibility of measuring the drug-specific levels, so as to estimate the anticoagulant effect of a DOAC, is also mentioned, although the authors are of the opinion that routine testing before the LP is not necessary. [1]
  We believe that this is a crucial point, above all in the case of an urgent or emergent LP. Indeed, in our experience, when available, drug-specific levels can be obtained quickly and guide the cl...

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  Dear Editor,
  We read the article by Dodd et al. (2018) [1] with great interest. The authors provide evidence-based recommendations for the periprocedural management of antithrombotic and anticoagulant treatment in patients who require a lumbar puncture (LP). Indeed, this is a very relevant practical point for neurologists, above all when an urgent diagnostic LP is mandatory to rule out an infectious disease of the central nervous system, or a subarachnoid hemorrhage. The recommendations on adjustment/reversal of warfarin for patients on oral anticoagulants, who require LP, are well known, i.e. long-term LP allowed if INR is < 1.4. Whilst the question of how to manage patients on Direct Oral Anticoagulants (DOACS), a relatively novel pharmacological class, is also to be answered. Dodd et al’s article [1] reports that if a non-urgent LP has to be carried out he these patients, current recommendations vary among different advisory bodies about the time lapse necessary for DOAC withdrawal before the LP, depending on the renal function. The interesting possibility of measuring the drug-specific levels, so as to estimate the anticoagulant effect of a DOAC, is also mentioned, although the authors are of the opinion that routine testing before the LP is not necessary. [1]
  We believe that this is a crucial point, above all in the case of an urgent or emergent LP. Indeed, in our experience, when available, drug-specific levels can be obtained quickly and guide the clinical management in this clinical setting. Notably, LP may be performed immediately, which may be clinically relevant, if the drug levels are under the cut-off chosen to rule out any anticoagulant effect. However, consensus is still lacking and different advisory bodies (French expert opinion, [2] Swiss operating procedures [3]) set the lower threshold limit for the anticoagulant effect of DOACs at a range between 20-50 ng/mL for other urgent procedures, like intravenous thrombolysis.
  Therefore, if there were an international, or at least European consensus on the recommended DOAC drug level cut-off to rule out any anticoagulant effect, the management of patients requiring urgent or emergent procedure, like LP or surgery, would be facilitated. Obviously, if the DOACs levels are within the therapeutical range, a delay before the LP is required, according to the recommendations.
  However, a remarkably different management may be prospected if an LP is indicated in patients is on dabigatran, where emergency reversal may be achieved by idarucizumab, as Dodd et al. [1] report, recommending previous consultation with a hematologist. This is another crucial point and a clinical novelty, where an urgent/emergent LP may be allowed in dabigatran-treated patients in only a few minutes after idarucizumab administration. Although literature evidence is still scarce and only a few cases (three, considering ours) have been reported to date, in our experience an LP after dabigatran emergency reversal by idarucizumab is a safe procedure, as was demonstrated by our two personal cases, one published, [4] one in press. Therefore, we are of the opinion that idarucizumab could be safely administered to patients requiring LP, also in the absence of a haematologist, to save the time inevitably required by the consultation.
  Another reversal agent, andexanet-alpha, was recently approved by the FDA and seems to be appealing for patients on direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), as Dodd et al. [1] report. However, the time required to reverse the DOAC effect and the putative pro-thrombotic effect of andexanet-alpha make it an unlikely candidate for an emergency reversal of direct factor Xa inhibitors before an LP.
  Lastly, Dodd et al. [1] recommend the DOAC first dose 6 hours after an atraumatic LP. We suggest the following algorhythm: in the presence of a CHADSVADSC score of >=3 administer the DOAC after 6 hours and after 12 hours with a CHADSVASC score of <3.
  It is, however, encouraging that a novel clinical scenario is emerging for the management of patients on DOACs, where outstanding opportunities are provided by the availability of specific DOAC levels dosages, even if international consensus would be welcome to set a clear cut-offs for the anticoagulant effect and, above all, by the reversal agent idarucizumab, which seems to be a safe and effective tool for urgent/emergent LP in dabigatran-treated patients.

  References
  1. Dodd KC, Emsley HCA, Desborough MJR, Chhetri SK. Periprocedural antithrombotic management for lumbar puncture: Association of British Neurologists clinical guideline. Pract Neurol. 2018 Aug 28. pii: practneurol-2017-001820. doi: 10.1136/practneurol-2017-001820. [Epub ahead of print]
  2. Touzé E, Gruel Y, Gouin-Thibault I, De Maistre E, et al. Intravenous thrombolysis for acute ischaemic stroke in patients on direct oral anticoagulants. Expert opinion of the SocieteFrancaise de NeurologieVasculaire (SFNV) and the GroupeFrancaisd'etudes sur l'Hemostase et la Thrombose (GFHT). Eur J Neurol 2018 Jan 23. doi: 10.1111/ene.13582.
  3. Seiffge DJ, Traenka C, Polymeris AA, et al. Intravenous Thrombolysis in Patients with Stroke Taking Rivaroxaban Using Drug Specific Plasma Levels: Experience with a Standard Operation Procedure in Clinical Practice. J Stroke 2017; 19(3): 347-355.
  4. Agosti S, Casalino L, Daffonchio A, Arena L, Celli L and Rota E. Emergency Lumbar Puncture for Suspected Meningitis after Dabigatran Reversal with Idarucizumab: A Case Report. J Clin Case Rep 2018, 8:4.

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  Conflict of Interest:
  None declared.

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