Safety of prothrombin complex concentrate for emergency surgery according to the oral factor xa inhibitor level

Abstract Background: The incidence of thrombotic events after use of 4-factor prothrombin complex concentrate (4F-PCC) for oral factor Xa inhibitors-(XaI)-associated major bleeding is 3-4% and 5% in a study on 4F-PCC for XaI and emergency surgery. Rapid anti-Xa assays are seldom available, prompting clinicians to frequently administer 4F-PCC empirically. It is unknown if the thrombotic risk increases when pre-operative levels are low or unmeasured. Methods: We analyzed retrospectively all patients that received 4F-PCC between September 2018 and July 2024 at the hospitals in Hamilton, Canada, and screened for those with emergency surgery/invasive procedure as main indication. The PCC used was almost exclusively Octaplex (Octapharma). The primary outcomes were symptomatic or asymptomatic, objectively verified arterial or venous thromboembolism within 7 days from PCC infusion. The secondary outcome was the same but between day 8 and 30 postoperatively, at which timepoint other causes than preoperative PCC may be more prominent. XaI levels were determined with an anti-Xa assay, calibrated with the respective DOAC used by the patient. All-cause mortality within 30 days was also captured. The study was approved by Hamilton Integrated Research Ethics Board. Results: PCC at a median dose of 2000 units (interquartile range, 2000-2000) was administered to 224 patients on apixaban (142; 63%), rivaroxaban (71; 32%) or edoxaban (11;5%) for emergency surgery or invasive procedures. Mean age was 74 years and 42% were female. Postoperative prophylaxis against venous thromboembolism was started promptly in 184 patients (82%) after a median of 1 day (interquartile range, 1-2). Among 36 patients with high XaI levels, defined as at least 75 ng/mL there was 1 pulmonary embolism (3%); 24 patients with low levels had no events; 164 patients without any level measured had 7 events (4%) within 7 days, consisting of 5 myocardial infarctions, 1 DVT, 1 cerebral infarct. Two additional cerebral infarcts were deemed to be caused by compressive intracerebral hematomas that were evacuated. Events between day 8-30 were only in the group with no level – 3 deep vein thrombosis, 1 pulmonary embolism, 1 arterial thrombus. There were 8 deaths (22%) in the XaI high-level group, 2 (8%) in the low-level group, and 15 (9%) in the no-level group. Conclusion: The risk of thromboembolic events after 4F-PCC for management of hemostasis in patients on XaI and emergency surgery/invasive procedures appears to be similar among patients with preoperative drug levels that are high, low or not measured. These findings support the safe use of PCC in settings where rapid anti-Xa testing is unavailable.