A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
Despite a lack of clinical data supporting their superiority, 4-factor PCCs have been universally accepted as the intervention of choice for the reversal of Warfarin induced bleeding. While PCCs have demonstrated rapid normalization of INR values, they have yet to show any added value over FFP in true clinically relevant endpoints. In the largest RCT to date, 4-factor PCC corrected INR values far faster than FFP but with a mortality rate that was almost double that of the FFP group. In a recent small RCT published in American Journal of Emergency Medicine, Karaca et al attempted to demonstrate that 4-factor PCCs provide more than just surrogate benefits when treating Warfarin induced gastrointestinal hemorrhage.
In this small unblinded trial, 40 patients with clinically suspected upper GI bleeds were randomized to have their coagulopathy reversed by either FFP or Cofact, a 4-factor PCC. The outcomes examined by the authors were INR values at 2 and 6 hours, time-to-endoscopy, and percentage of patients with active hemorrhage at time of endoscopy (based on the Forrest Classification). Patients were required to have their INR level reach 2.1 before undergoing definitive endoscopic interventions. As is typical in FFP vs PCC trials, the dose of FFP used was bordering on a straw man dose at 10-15 cc/kg.
To what should be no one’s surprise, 4-factor PCC reduced INR levels significantly faster than FFP, and thus patients in the PCC group underwent endoscopy earlier than their FFP counterparts. Patients in the PCC group received their endoscopy on average at 8 hours after admission, while the FFP group underwent endoscopy closer to the 12 hour mark. Endoscopy revealed more patients with active hemorrhage (Forrest Classification 1a or 1b) in the FFP group (7 patients vs 0) and sclerotherapy was performed in 10 patients in the FFP group, with 1 in the PCC group. Furthermore 3 patients in the FFP group required further therapy due to rebleeding, while no events of rebleeding occurred in the PCC group.
These superiorities in surrogate and pseudo-surrogate endpoints did not translate into the patient oriented endpoint of mortality, which was equivalent (one patient in each group). As far as the dreaded complication of “thrombolic events” that has been associated with PCC use it is somewhat unclear. One patient in the PCC group experienced a fatal IVC thrombosis but authors claim this condition was a presenting malady rather than an adverse event due to the administration of PCC.
Once again PCC has found success upon examination of soft endpoints. In an unblinded trial with surrogate and subjective endpoints, it is unclear if the PCC group’s performance was due to the medication’s efficacy or simply random chance and a small cohort. Until superiority in concrete clinically relevant outcomes is demonstrated, we should be wary of the crown of supremacy PCCs currently flaunt.
“Use and effectiveness of PCC vs FFP in gastrointestinal hemorrhage due to warfarin usage in the emergency department”