Direct oral anticoagulants (DOACs) have revolutionized the management of atrial fibrillation (AF), significantly reducing the risk of ischemic stroke.¹ However, the associated risk of intracerebral hemorrhage (ICH), though rare, remains a serious concern with high mortality rates.² To mitigate the impact of DOAC-associated ICH, the use of prothrombin complex concentrate (PCC) as a hemostatic treatment has been widely adopted, despite limited clinical evidence.² A recent population-based study conducted by researchers at the Chinese University of Hong Kong (CUHK) revealed that PCC did not significantly improve neurological recovery or reduce mortality in AF patients experiencing DOAC-associated ICH.² These findings call for a reassessment of current treatment protocols and highlight the urgent need for alternative strategies to manage this critical complication.²

AF is a prevalent cardiac arrhythmia defined by disorganized atrial electrical activity, leading to irregular ventricular response and compromised hemodynamic efficiency.³ This dysrhythmia predisposes to thrombus formation within the atria, increasing the risk of cardioembolic events, particularly ischemic stroke, due to embolization of clots to cerebral circulation.^3-4 DOACs are routinely prescribed for AF patients to prevent such clots, reducing the risk of moderate to severe stroke by 44%.⁵ However, the use of DOACs also carries a potential downside - an increased risk of bleeding.^1,2 The risk of ICH in patients taking DOACs is rare (approximately 0.1%), but this may lead to the compression of brain tissue and disrupt blood flow, resulting in significant disability and a high mortality rate, reaching up to 40%.^2,6 Therefore, timely and effective hemostatic treatment is critical for patients experiencing DOAC-associated ICH.^1,2

Traditionally, the management of DOAC-associated ICH involves careful monitoring of blood pressure and, in some cases, the administration of PCC to replenish depleted coagulation factors.^1,2 Despite being a common treatment choice, the use of PCC in such cases has been based largely on expert opinion and animal model studies, with limited human clinical data to substantiate its effectiveness.^1-2

A recent study led by Dr. Bonaventure Ip Yiu-Ming, Clinical Assistant Professor at the Division of Neurology, Department of Medicine and Therapeutics at CUHK, analyzed data from the Hospital Authority Data Collaboration Laboratory (HADCL) and the territory-wide DOAC Registry to address this gap in evidence.² The research focused on 232 anonymized AF patients who developed DOAC-associated ICH between 2016 and 2021.² Using artificial intelligence (AI) imaging analysis, developed in collaboration with CUHK’s Department of Imaging and Interventional Radiology and Department of Computer Science and Engineering, the team conducted a population-based, propensity score-weighted retrospective cohort study.² They compared outcomes between patients treated with PCC (25IU/kg-50IU/kg) and those managed conservatively without hemostatic agents.² The primary outcome was a modified Rankin scale score of 0-3 at three months, indicating a return to baseline functional status, while secondary outcomes included 90-day mortality, in-hospital mortality and hematoma expansion.²

The study revealed that only 31% of the patients achieved good neurological recovery, while 39% died within 90 days of their ICH event.² Weighted logistic regression analysis showed no significant association between PCC use and improved neurological recovery (adjusted odds ratio [aOR]=0.62; 95% CI: 0.33-1.16; p=0.14), 90-day mortality (aOR=1.03; 95% CI: 0.70-1.53; p=0.88), in-hospital mortality (aOR=1.11; 95% CI: 0.69-1.79; p=0.66), or reduced hematoma expansion (aOR=0.94; 95% CI: 0.38-2.31; p=0.90) when compared to conservative management.²

In summary, these findings challenge the current clinical approach to managing DOAC-associated ICH with PCC, which, despite being widely used, showed no clear clinical benefit in this cohort of patients.² Given the unique challenges posed by DOAC-associated ICH, particularly in Asian populations, future studies should prioritize the development of individualized treatment protocols that account for patient-specific factors such as hematoma size, Glasgow Coma Scale scores, and the presence of intraventricular hemorrhage.^1,2