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American Journal of Emergency Medicine xxx (2015) xxx–xxx
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American Journal of Emergency Medicine
journal homepage: www.elsevier.com/locate/ajem
Case Report
Prothrombin complex concentrate administration through intraosseous
access for reversal of rivaroxaban
A 64-year-old man presented to the emergency department with complaints of abdominal pain and rectal bleeding as well as extensive bruising
on his arms and legs. The patient was discharged from an outside hospital
2 days prior on rivaroxaban for a deep vein thrombosis and clopidogrel for
a recent non–ST elevation myocardial infarction. Upon arrival, he was
awake, alert, and oriented with a blood pressure of 77/55 mm Hg, heart
rate of 62 beats per minute, and oxygen saturation of 96% on room air.
Initial point-of-care hemoglobin was 4.5 g/dL. Due to concern for bleeding,
low blood pressure and perceived difficulty in obtaining intravenous
access, intraosseous (IO) access was obtained. After IO placement, the patient experienced significant pain and was unable to tolerate large volumes
administered through the IO. Given the low hemoglobin and inability to
obtain other laboratory test results, Profilnine SD (factor IX complex
[human] [factors II, IX, X]) 1490 U was administered to help to replenish
the factor X that the rivaroxaban was inhibiting. This prothrombin complex
concentrate has a much smaller volume compared with blood products
and was tolerated without complication. This is the first reported case of
administration of prothrombin complex concentrate via IO access.
Rivaroxaban is a new oral anticoagulant (NOAC) indicated for deep
vein thrombosis, pulmonary embolism, and nonvalvular atrial fibrillation. Bleeding is a major adverse effect reported with rivaroxaban.
Only blood products are available to try and correct bleeding caused
by NOACs. Prothrombin complex concentrates (PCCs) have been
thought to replace factors that NOACs inhibit. Profilnine is a 3-factor
PCC that includes factors II, IX, and X. Administration of PCC via the
intraosseous (IO) route has not been previously described in the literature.
We present a case in which 3-factor PCC (Profilnine) was successfully
administered via IO access to treat bleeding caused by a NOAC.
A 64-year-old man presented to the emergency department by ambulance with a complaint of abdominal pain and melena. He was noted
to have extensive bruising on all extremities. His medical history included non–ST elevation myocardial infarction, pacemaker, chronic
hyponatremia, adrenal insufficiency, and myositis. Pertinent medications that the patient was receiving upon discharge from an outside
hospital 2 days prior were rivaroxaban 15 mg orally twice a day for
lower extremity deep vein thrombosis and clopidogrel for recent non–
ST elevation myocardial infarction. Initial vitals were blood pressure of
77/51 mm Hg, hear rate of 62 beats per minute, oxygen saturation of
96% on room air, and point-of-care hemoglobin (POC Hgb) of 4.5 g/dL.
There was apprehension about attempting intravenous (IV) access because of the patient's bruising/bleeding, POC Hgb, and declining blood pressure. After numbing the area, IO access was placed without discomfort into
the patient's right humerus. He experienced significant pain while it was
flushed with normal saline. Lidocaine 10 mg was instilled without relief.
The patient continued to experience significant pain as the IO was flushed,
despite 3 doses of fentanyl 25 μg IO. Based on volume and availability,
Profilnine PCC was used. Profilnine 1490 U (33 U/kg) was reconstituted
with 10 mL of manufacturer provided diluent and administered at its maximum rate of 10 mL/min via the IO line. The patient experienced pain during
the infusion; however, no other adverse reactions during or after the dose.
The patient was transferred to the medical intensive care unit for
further management where they were able to place an ultrasoundguided IV line. Blood pressure improved to 90s/50s mm Hg and
hemoglobin (Hgb) was 8.9 g/dL from a venous blood draw 1 hour after
Profilnine administration. The patient received an esomeprazole infusion
and 2 U of packed red blood cells. The following morning his Hgb
decreased (6.1 g/dL); 2 days later, his Hgb was 10.2 g/dL. Laboratory
monitoring could not be performed to confirm Profilnine aided in ceasing
bleeding; however, the patient did not experience any additional melena
and hemodynamics stabilized. Unfortunately, because of the patient's
other medical conditions, the patient transitioned to comfort care.
Patients who cannot get IV access may be a candidate for IO vascular
access [1,2]. The IO route is a noncollapsible access site that can be
obtained quickly and is often used in the prehospital setting. A majority
of medications can be administered through the IO route at the same
dose as for the IV route. If conscious patients experience pain, the
manufacturer recommends instilling lidocaine 40 mg into the IO [3].
Lidocaine 10 mg was used due to the patient's cardiac history and
concern that systemic lidocaine could cause additional adverse events.
Unfortunately, the patient did experience significant pain through the
IO, even after administration of lidocaine and fentanyl.
Rivaroxaban is a reversible inhibitor of factor Xa [4]. Some potential
proposed advantages to the NOACs are lack of routine monitoring and
dose adjustments; however, there are no antidotes available [5]. The PCC
products are hypothesized to aid in the reversal of NOACs, although PCC
products differ in the factors that they possess. Because of the volume of
the blood transfusions, patient tolerance, and the critical nature of the clinical picture in conjunction with the POC Hgb, it was decided to use
Profilnine to help reverse the rivaroxaban. This PCC was selected because
it could help reverse the rivaroxaban by supplying additional factor X.
The same dose that would be ussed IV was given to the patient IO without
adverse effects. There are currently no published cases of any PCC product
being administered IO. Fresh frozen plasma has been used to try to aid in
reversal of rivaroxaban, and blood products may be administered IO per
the EZ-IO manufacturer. The advanced trauma life support guidelines recommend blood transfusions through the IO; however, there are concerns
for hemolysis of blood transfusions due to shearing forces [6,7]. Burget
et al [8] report administration of blood through a tibial IO in a 79-yearold woman with hemorrhage. There was no comment on the patient's
blood counts to evaluate patient response. No other case reports of blood
transfusions through the IO were available at the time of this case.
0735-6757/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Means L, Gimbar RP, Prothrombin complex concentrate administration through intraosseous access for reversal of
rivaroxaban, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.07.057
2
L. Means, R.P. Gimbar / American Journal of Emergency Medicine xxx (2015) xxx–xxx
Profilnine was used to treat a bleeding patient with IO access. It
appears that Profilnine is well tolerated IO; however, further studies
are needed to evaluate if this is an effective practice.
Laura Means PharmD ⁎
Renee Petzel Gimbar PharmD⁎⁎
Department of Pharmacy Practice, University of Illinois at Chicago
College of Pharmacy, Chicago, IL
Hospital Pharmacy Services, University of Illinois Hospital and Health
Sciences System, Chicago, IL
⁎
Correspondence to: L. Means, UK Health, 800 Rose Street
Room H-110, Lexington, KY 40536. Tel.: +1 248 974 9707
⁎⁎
Correspondence to: R.P. Gimbar, University of Illinois at Chicago
College of Pharmacy, 833 South Wood Street, 164 PHARM
Chicago, IL 60612. Tel.: +1 312 413 9828
Email addresses: [email protected], [email protected]
[email protected]
References
[1] Fowler R, Gallagher JV, Isaacs SM, Ossman E, Pepe P, Wayne M. The role of
intraosseous vascular access in the out-of-hospital environment. Prehosp Emerg
Care 2007;11(1):63–6.
[2] Anson JA. Vascular access in resuscitation: is there a role for the intraosseous route?
Anesthesiology 2014;120(4):1015–31.
[3] “Consider using anesthetic for patients responsive to pain”. EZ-IO Device Comfort.
http://www.eziocomfort.com/ezio-comfort.html#dosing-&-administration.
[4] Lexicomp. Rivaroxaban. Accessed September 3, 2015.
[5] Nutescu EA. New approaches to reversing oral anticoagulant therapy. Am J Health
Syst Pharm 2013;70(1):S1–2.
[6] The 5 rights of intraosseous vascular access. [PDF document]. Retried from site:
http://www.utmb.edu/edlab/ezio/TrainingPDFNotes/5%20Rights%20Notes%20Pages%
20Rev.
[7] Harris M, Balog R, Devries G. What is the evidence of utilize for intraosseous blood
transfusion in damage-control resuscitation? J Trauma Acute Care Surg 2013;
75(5):904–6.
[8] Burget JM. Intraosseous infusion of blood products and epinephrine in an adult
patient in hemorrhagic shock. AANA J 2009;77(5):359–63.
http://dx.doi.org/10.1016/j.ajem.2015.07.057
Please cite this article as: Means L, Gimbar RP, Prothrombin complex concentrate administration through intraosseous access for reversal of
rivaroxaban, Am J Emerg Med (2015), http://dx.doi.org/10.1016/j.ajem.2015.07.057