Written by: Mediware Consulting and Analytics on Wednesday, April 6, 2016 Posted in: Blood Management

Plasma Transfusion and Neuroaxis Procedures

The primary question surrounding the need or indication for plasma transfusion in patients undergoing neuro-axis anesthesia must be considered differently based on two clinical populations, specifically those patients taking anticoagulants and those who are not.

We shall consider the latter population first and this will include those undergoing major neurosurgical procedures not just spinal anesthesia.

For patients NOT on anticoagulant medications, there is currently no clear

evidence that a definitive PT/INR, platelet count, or aPTT will predict bleeding. Historically, not based on clinical outcomes or solid science, an abnormal PT was defined as 1.5X the upper limit of the normal reference range (NRR). This was prior to the initiation of the INR which we must remember was a mathematical calculation introduced to help standardize inter-laboratory therapeutic targets for PT results in patients on warfarin for antithrombotic therapy. There is, thus, a therapeutic range for INR but not a true normal range. (Interestingly, it is a requirement of CLIA that all laboratories provide NRRs. In some situations this is counterintuitive. Think of this similar to “normal” drug levels in blood, when actually there are no such beasts, only therapeutic targets for specific drugs.) In fact, as shown by Holland et al. even normal whole blood donors may have calculated INRs of 1.4 which would be “outside” the common NRRs listed by most labs. This is due to the variability in coagulation factor activity in normal people and also that the INR does not have a linear relationship to these levels. Holland’s subsequent study showed transfusion of plasma to patients with “abnormal” INRs would not consistently change this value to <1.7 in the majority of cases. Note the graph correlates an INR of 2.0 to represent coagulation factor % activity of 25-30% which confers sufficient clotting activity for adequate hemostasis. Even hemophiliacs do not bleed spontaneously until the Factor VIII or IX level respectively is below 5-10%. A nicely done study by Abdel-Wahab showed no effect on bleeding outcomes across a broad range of invasive procedures in patients with INRs as high as 1.9. This prompted the Patient Blood Management/Transfusion Medicine base to recommend against prophylactic plasma transfusion in patients with mild to moderate elevations of INR defined as <2.0.   The Yang et al. meta-analysis and the recent TOPIC trial by Muller and coauthors support this message.

For those patients undergoing major invasive neurosurgical procedures or with significant neurosurgical diagnoses, “abnormal” coagulation tests are not predictive or associated with bleeding. Matevosyan et al. demonstrated that INRs of 1.7 indicate hemostatically normal levels of coagulation factors. The study by Schramm showed no evidence that PT/INR or platelet count predicted bleeding. In fact, > 55% of bleeding in neurosurgical patients undergoing craniotomies and spine surgeries was in patients without abnormal coagulation values. History of bleeding was a key factor in assessing bleeding risk. Another study by Davis and colleagues looked at placement of ICP monitors and abnormal coagulation tests. Three clinically insignificant petechial hemorrhages occurred in their study population and two of those had INRs of 1.2 and 1.3 respectively, considered “normal”. They comment that unnecessary plasma transfusion could be associated with worse outcomes as this causes delay in ICP monitor placement and necessary aggressive treatment of this pressure. If one looks at the incidence of hematoma after spinal anesthesia overall, one large study of over 850,000 procedures found the risk to be estimated as 1:280,000 (see Stafford-Smith).

The most recent ASA published guidelines for PBM strategies uses an INR >2.0 in their table for indications for plasma transfusion. There is no mention in their discussion of need for an INR of 1.5. Note the use of plasma is also for the bleeding patient i.e. for therapeutic not prophylactic treatment. (As an aside…interestingly, the ASA document mentions “in the absence of heparin”. We all know that the INR is not used to monitor heparin therapy/levels and that excessive heparin would be reversed using protamine sulfate.)

Now, if we examine the patient taking anti-thrombotic medication and in whom neuro-axis anesthesia/intervention is being considered, then the primary guiding principle is timing, i.e. the minimal time of the last dose prior to intervention and the minimal time prior to re-initiation of the necessary anticoagulant. Current guidelines clearly include this. The ASRA, Stanford and NYSORA mention the 1.5 INR target for patients on warfarin therapy. Again, this does not necessarily translate to patients NOT on warfarin and I would respectfully disagree with the use of 1.5 even in this population given the previously discussed literature. This target is not evidence-based, but consensus- based. The most recent study by Gulur saw the average INR of 1.69 which is at least more in line with the Matevosyan study. We must remember that patients on anticoagulant medications are pro-thrombotic and over-correction of the INR in those on warfarin may be just as, or even more risky. Also, patients on LMWH, anti-Xa or DTIs are not followed with PT/INR measurements and plasma is not recommended for reversal even in the bleeding patient.

Bottom line, there is no current evidence that outside of exsanguinating hemorrhage, plasma transfusion confers any benefit for patients and actually incurs significant risk in terms of TACO, TRALI and allergic/anaphylactoid adverse events. With the recent approval of additional antidotes for the old and new targeted anticoagulants, plasma use in the bleeding patient on antithrombotic therapy can and should be reduced. Of course these drugs are not to be used in stable non-bleeding patients.

References:

  • Stafford-Smith. Can J Anaesthesiol 1996; 43: R129
  • Schramm et al. Anesthes Intens Care 2001; 29: 388
  • Davis et al. J Trauma 2004; 57: 1173
  • Holland et al. Transfusion 2005;45: 1234
  • Abdel-Waha et al. Transfus 2006; 46: 1279
  • Horlocker et al. Reg Anesthes and Pain Med 2010; 35: 64
  • Matevosyan et al. J Neurosurg 2011; 114: 3
  • Horlocker. Brit J Anaesthes 2011; 107: i96
  • Yang et al. Transfus 2012; 52: 1673
  • Muller et al. Transfus 2015; 55: 26
  • Gulur et al. Brit J Anaesthes 2015; 114: 808
  • Stanford University Anticoagulation Guidelines for Neuraxial Procedures   www.ether.stanford.edu
  • NYSORA Regional Anesthesia in the Anticoagulated. www.nysora.com

 

Author: Carolyn Burns, MD