Impact of a Pharmacist-Driven Prothrombin Complex Concentrate Protocol on Time to Administration in Patients With Warfarin-Associated Intracranial Hemorrhage

Jessica L. Corio, PharmD; Jonathan H. Sin, PharmD; Bryan D. Hayes, PharmD; Joshua N. Goldstein, MD, PhD; Lanting Fuh, PharmD


Western J Emerg Med. 2018;19(5):849-854. 

In This Article


Overall, we found that our change in protocol was associated with a 35-minute decrease in time to administration of 4F-PCC for warfarin-associated ICH in the ED. Numerous changes were made simultaneously, including the need for approval, the use of a pharmacist at the bedside, and the change in storage location leading to more rapid accessibility. The pharmacist also played an active role in dosing the reversal agent accordingly, based on the patient's INR and weight, and served as a resource at the bedside for answering staff questions regarding administration and monitoring.

Prior to implementation of the pharmacist-driven protocol, 4F-PCC was purchased by and stored within the blood bank. Ownership of the product was transferred from the blood bank to the Department of Pharmacy in April 2016 and is now purchased under the department's budget. The protocol was developed in conjunction with the transfer of ownership.

Other institutions have performed similar analyses of systems changes. Through changing the approval process to include stroke physicians, implementing point-of-care INR testing, and moving a stock of 4F-PCC to the ED, one UK institution was able to decrease time to administration from a median of 127 minutes (IQR, 111–208) to 58 minutes (IQR, 5091).[10] A Canadian institution developed a new protocol to replace written orders sent to the blood bank for 4F-PCC with a verbal order from the ED attending, and designated a specific orderly to retrieve the prepared product from the blood bank, leading to a 40-minute improvement in time to administration.[12] With our new protocol in place, the time to 4F-PCC administration improved by a median of 35 minutes, which is comparable to previous reports demonstrating an improved administration time of 30–58 minutes after protocol implementation.[10–12]

A number of factors can lead to delays in 4F-PCC administration in a real-world setting. Pre-intervention, numerous steps were required to obtain 4F-PCC, and it is not clear which steps required more or less time. Post-intervention, fewer steps were required, a dedicated pharmacist was readily available, and the primary storage location was a medication-dispensing cabinet within the ED. While both protocols required an approval service, the blood-bank fellow in the pre-protocol group and the pharmacist in the new protocol group, the pharmacist may already be actively involved in other facets of the patient's care and can assess the patient earlier in their ED visit. However, it is unclear whether the presence of the pharmacist, the fact that fewer steps were necessary, or an unmeasured confounder led to the changes in administration times. One strength of our study is that the data represent a real-world setting of 4F-PCC administration, rather than the controlled environment and selected patients in a clinical trial.

There are no guidelines regarding optimal time to administration of anticoagulation reversal agents in relation to clinical outcomes and mortality. Though this study demonstrated a reduced time to administration, it was not powered to detect differences in clinical outcomes. Recent literature comparing 4F-PCC to FFP in the setting of warfarin-induced ICH has suggested faster reversal may be associated with a lower risk of hematoma expansion.[13–14] While it is known 4F-PCC more rapidly reverses the INR in comparison with FFP, it remains unclear how soon 4F-PCC should be administered after the onset of warfarin-associated ICH and if there are any clinically significant benefits with faster reversal. Further study is needed to assess clinical measures and outcomes in earlier reversal of anticoagulation for warfarin-associated ICH and the optimal timeframe for 4F-PCC administration.