Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants

Abstract

ImportanceIntracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear.ObjectiveTo compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management.Design, Setting, and ParticipantsIn this population-based, propensity score–weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023.Main Outcomes and MeasuresThe primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified.ResultsA total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion.Conclusions and RelevanceIn this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Reply to “Letter to Dobesh et al. on lower mortality with andexanet alfa in factor Xa inhibitor–related major bleeding”

“…Contrary to the final remarks from Lucarelli et al. [ 1 ], our findings, along with those of other recent observational as well as randomized trials [ 5 , 6 , 8 ], do help inform clinical practice.…”

“…[ 1 ] was designed to assess hemostatic efficacy, and the imaging component of limiting hematoma expansion was achieved in 77% of patients treated with andexanet alfa vs 65% of patients treated per usual care, the majority of whom received 4F-PCC [ 5 ]. The observed 35% hematoma expansion with usual care in ANNEXA-I may suggest little to no benefit with PCC in factor Xa (FXa) inhibitor–related bleeds based on its inability to effectively lower FXa levels, in alignment with findings from other studies [ 6 ]. Hematoma expansion is associated with poor functional outcomes and an increased risk of death after ICH.…”