A Protocol for the Rapid Normalization of INR in Trauma Patients with Intracranial Hemorrhage on Prescribed Warfarin Therapy

Abstract

Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.

The Efficacy of Factor VIIa in Emergency Department Patients With Warfarin Use and Traumatic Intracranial Hemorrhage

“…We were, however, unable to demonstrate any difference in patient‐oriented outcomes (mortality or discharge GOS). The inability to translate normalization of INR to improved patient‐oriented outcomes is consistent with other studies 25,36,37 . The lack of improvement of mortality is also seen in studies involving much higher doses of rFVIIa 24 and multiple doses of rFVIIa 23 .…”

Urgent reversal of vitamin K antagonist therapy

“…Overall, only one of the studies demonstrated a difference in clinical outcome 43 . Several studies showed faster and more efficient correction of INR with PCC compared with FFP 37,38,40,41 . However, the majority of the studies have an impaired methodology either due to a poor design with a historic control group, 37,42 or a limited number of patients, 40,41 or incomparable patient groups 37 .…”

“…Several studies showed faster and more efficient correction of INR with PCC compared with FFP 37,38,40,41 . However, the majority of the studies have an impaired methodology either due to a poor design with a historic control group, 37,42 or a limited number of patients, 40,41 or incomparable patient groups 37 . The majority of clinical studies have been carried out in patients with intracranial haemorrhage, as this serious complication requires fast reversal of VKA therapy to diminish the injury caused by ongoing haemorrhaging.…”

“…Four of the five studies concerning patients in VKA therapy with intracranial haemorrhage, either provide no information on these issues or have an unequal distribution between the study groups 38–40,43 . For the remaining two studies concerning acute haemorrhaging in patients with VKA treatment, there is either no information on INR levels at admission 37 or a higher mean pre‐treatment INR in the FFP group compared with the PCC group 42…”

“…Among all patients treated with PCC in therapeutic doses, 37–50 serious adverse effects were reported in 11 patients (2.2%). Of these, seven could be related to PCC (1.4%).…”