Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Association of oral anticoagulants with risk of brain haemorrhage expansion compared to no-anticoagulation

Neurological Research and Practice volume 7, Article number: 12 (2025) Cite this article

Abstract

Background

The impact of direct oral anticoagulants (DOAC) on haematoma size after intracerebral haemorrhage (ICH) compared to no-anticoagulation is controversial and prospective data are lacking.

Methods

The investigator-initiated, multicentre, prospective RASUNOA-prime study enrolled patients with non-traumatic ICH and atrial fibrillation while on a DOAC, vitamin K antagonist (VKA) or no anticoagulation (non-OAC). Neuroimaging was reviewed centrally blinded to group allocation. Primary endpoint was haematoma expansion (≥ 6.5 ml or ≥ 33%, any new intraventricular blood or an increase in modified Graeb score by ≥ 2 points) between baseline and follow-up scan within 72 h after symptom onset.

Results

Of 1,440 patients screened, 951 patients with ICH symptom onset less than 24 h before admission were enrolled. Baseline scans were performed at a median of 2 h (IQR 1–6) after symptom onset. Neurological deficit and median baseline haematoma volumes (11 ml; IQR 4–39) did not differ among 577 DOAC, 251 VKA and 123 non-OAC patients. Haematoma expansion was observed in DOAC patients in 142/356 (39.9, 95%-CI 34.8–45.0%), VKA in 47/155 (30.3, 95-CI 23.1%–37.6%), versus non-OAC in 22/74 (29.7, 19.3–40.1%). Unspecific reversal agents in DOAC-ICH (212/356, 59.6%) did not affect the haematoma expansion rate compared to no-antagonization.

Conclusion

Baseline haematoma volume and risk of haematoma expansion did not differ statistically significantly in patients with and without DOAC.

Introduction

Intracranial haemorrhage develops in 0.07 to 0.5% of patients anticoagulated with a direct oral anticoagulant (DOAC) annually [1], which results in death in 24 to 67% of patients and significant disability in intracerebral haemorrhage (ICH) survivors [2,3,4,5,6]. Haematoma size is a key prognostic factor in ICH [7]. A therapeutic target after ICH in general and in OAC-related ICH in particular is to prevent early haematoma expansion [8, 9]. Although solid evidence from prospective studies regarding the putative excess risk of haematoma expansion in DOAC-ICH compared to no anticoagulation is missing, current guidelines—in analogy to vitamin K antagonists (VKA)-ICH—recommend that management of DOAC-ICH should comprise anticoagulant reversal [10, 11]. The specific reversal agents idarucizumab and andexanet alfa have been licensed for reversing the anticoagulant effect of dabigatran and two factor Xa inhibitors, respectively. Recently, for andexanet alfa a reduction of haematoma expansion rates compared to a group receiving mostly prothrombin complex concentrate (PCC) was shown in a randomized trial [12]. However, detailed evidence regarding the characteristics of DOAC-ICH in comparison to non-anticoagulated atrial fibrillation (AF) patients with ICH from prospective studies in clinical routine is needed to further understand the characteristics of haematoma expansion and the potential usefulness of haemostatic measures in acute DOAC-ICH.

The aim of our prospective multicentre study was to describe the characteristics of ICH in AF patients receiving one out of three different types of treatment at the time of the ICH: (1) DOAC, (2) VKA or (3) no anticoagulation. We hypothesized that, in terms of substantial haematoma expansion rates, DOAC treatment before ICH is not inferior to no anticoagulation in AF patients experiencing ICH.

Methods

Study design and selection criteria

The Registry of Acute Stroke under Novel Oral Anticoagulants-Prime (RASUNOA-prime) was a prospective, multicentre, observational registry study of patients with AF and acute ischemic stroke or ICH (clinicaltrials.gov, NCT02533960). The ethics committee of the Medical Faculty of the University Heidelberg as well as all local ethics committees approved the study protocol (S-088/2015). Details of the study design have been published [13]. Herein, we report on the pre-specified study of patients with ICH. The study was conducted between 2015 and 2021 in 46 certified German and Austrian Stroke Units where consecutive patients with spontaneous non-traumatic ICH and AF were enrolled. Patients were eligible if they were 18 years or older and either the patient or a legal representative provided consent. Informed consent could be waived if patients were not able to consent and died before a legal representative could be installed. Exclusion criteria encompassed symptom onset of more than 24 h before admission, traumatic ICH and treatment with a parenteral anticoagulant.

Three groups were studied: (1) patients with evidence of intake of a DOAC (apixaban, dabigatran, edoxaban or rivaroxaban), (2) patients taking a VKA, and (3) patients not taking an anticoagulant (non-OAC) at the time of the ICH. Non-OAC included patients in whom prescription of a DOAC or VKA had been discontinued and in whom the last dose of a DOAC was given ≥ 72 h or a VKA ≥ 7 days before admission, respectively.

To ensure that all three treatment arms are equally distributed at any time of recruitment, reflecting potentially changing clinical practice and recommendations, enrolment followed a standardised algorithm in which each site had to recruit an ICH patient on a DOAC first and only subsequently was allowed to enrol patients into the two other study arms. Hereby, potential changes in the treatment of ICH patients over time is taken into account by obtaining controls (VKA or no-anticoagulation) each time a case (DOAC) is enrolled [13]. Three-month survival was ascertained either by a questionnaire, a phone call to patients or their designated representatives or by contacting the registration office.

Neuroimaging analysis

Each brain scan (computed tomography [CT] or magnetic resonance imaging [MRI]) was assessed using Osirix Pro software (Version 12 or newer) at the central imaging core laboratory by two trained, independent reviewers, and in case of disagreement, by a third reviewer, all of whom were blinded to group allocation. The analysis followed a pre-specified imaging analysis manual. Haematoma volume was measured by planimetry after reviewers had encircled intracerebral haematomas, excluding intraventricular blood (IVH) (as done previously [3]). To capture the entire spectrum of ICH encountered in clinical routine, follow-up brain imaging was not a mandatory study procedure because additional radiation exposure would have required prior consent. The development of haematoma volume was assessed on all available follow-up CTs or MRIs that had been performed within 72 h of symptom onset. The upper time limit was chosen as relevant residual DOAC activity is considered unlikely even in patients with renal failure 72 h after last intake. The modified Graeb score was calculated [14]. Substantial haematoma expansion was defined if haematoma volume on follow-up scans exceeded the baseline haematoma volume by ≥ 6.5 ml or ≥ 33%, or new intraventricular haemorrhage was found or intraventricular haematoma increased by ≥ 2 points on the mGraeb scale. Images were evaluated for haematoma expansion if no surgical haematoma evacuation or external ventricular drainage was evident before the respective follow-up scan.

Statistical analysis

The statistical analysis followed a pre-specified statistical analysis plan and was performed according to the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies. Although the study was observational, a primary hypothesis was made that the proportion of haematoma expansion in DOAC-ICH is not inferior to ICH without prior OAC. Sample size estimates were made based on the assumption that in non-OAC ICH patients, the rate of relevant haematoma expansion is approximately 28% [13]. We considered a clinically relevant increased risk of haematoma expansion if the rate in DOAC-ICH was more than 10% above this rate. To detect non-inferiority by a one-sided unpooled two-sample z-test with an alpha of 2.5%, a power of 80% and assuming a drop-out rate of 5%, 333 patients were needed per group. The recruitment strategy was modified in October 2019 after N = 651 patients had been enrolled and it had become clear that the originally planned sample size distribution per group could not be reached because ICH in patients with AF occurred much more frequently while receiving a DOAC or a VKA than in patients not receiving anticoagulants. Thereafter, recruitment was continued until nearly 1000 ICH patients were enrolled, irrespective of group allocation.

As no comparison of VKA and DOCA was intended, DOAC and VKA were compared against non-OAC separately. Comparison of two groups (DOAC vs. non-OAC or VKA vs. non-OAC) and exploratory analysis of subgroups (with/without radiological follow-up; anticoagulation reversal within DOAC; within VKA-ICH) was conducted by applying the Chi2-test or t-Test or Mann–Whitney U Test, according to the corresponding data measurement scale and properties of the observed distributions. The analysis of the primary outcome was a test of non-inferiority (Farrington-Manning score test) at significance level 2.5% using the pre-defined non-inferiority margin of 10%. After that a further non-inferiority test comparing VKA vs. non-OAC was conducted, using the same margin (secondary analysis). For all further analyses, the significance level was set to 5%. To include factors potentially affecting haematoma expansion rates the comparison was adjusted using stepwise modelling. In a first step, univariable and multivariable logistic regression (model 1) for haematoma expansion adjusting for pre-defined confounders (age, onset to brain imaging in hours, baseline haematoma volume, systolic blood pressure, concomitant antiplatelet therapy, ICH localization and pre-stroke mRS score (0–3 vs. 4–5, not documented) without the factor anticoagulation scheme at index event was conducted. The model-predicted logit (multivariable) of the event was used as a risk score in the subsequent analysis. In a second step, to compare DOAC vs. non-OAC and VKA vs. non-OAC separately, two logistic regression analyses were performed (model 2), each adjusted for the risk score out of the resulting model in step 1. A sensitivity analysis for the primary endpoint counting patients with early death (within the first day) as having the primary endpoint was also analysed. A second sensitivity analysis for the primary endpoint regarding effects of sites using generalized linear mixed models adjusted for random effects of centres was conducted.

Results

Out of 1,440 screened patients, 951 met the eligibility criteria and formed the “baseline cohort”.

Main characteristics of the baseline cohort are shown in Table 1 and additional characteristics in the online supplementary table S1. Overall, mean age was 79.1 (± 8.1) years and 45.1% were female. No differences were present among groups except for type of AF, a less frequent history of previous ICH in DOAC (3.5%) and VKA (2.0%) vs. non-OAC patients (10.5%), and a higher rate of antiplatelet therapy in non-OAC patients. Furthermore, pre-stroke mRS was lower in the VKA group compared to non-OAC. At hospital admission, neurological deficit and disability scores did not differ between anticoagulated and non-anticoagulated patients.

Table 1 Main characteristics of the ‘baseline cohort’ by anticoagulation scheme
Full size table

The first brain scan was performed at a median of 2 h (IQR 1–6) after symptom onset. Median baseline haematoma volume did not differ significantly among groups at this early time point (Table 2). Overall, any ventricular haemorrhage had developed in 43.3% of patients. No significant differences among groups were noted regarding median length of hospital stay, in-hospital mortality, and mortality at 3 months (Tables 1 and S1).

Table 2 Radiological characteristics of the ‘baseline cohort’ by anticoagulation scheme
Full size table

Haematoma expansion

The “haematoma expansion analysis cohort (HE-cohort)” comprised 585 patients with available follow-up scans within 72 h after symptom-onset and no early intracranial surgical treatment. Decisions not to perform follow-up imaging was made by local physicians including decisions for early palliative care (49%; Table S2). Figure 1 illustrates the patient flow.

Fig. 1
figure 1

Flow chart of patient enrolment

Full size image

Compared to patients without radiological follow-up patients in the ‘HE-cohort’ were younger, had a lower NIHSS score at admission and the baseline haematoma volume was smaller (suppl. Table S2). No differences were present among groups except that the non-anticoagulated group included more patients with previous ICH (suppl. Table S3).

Substantial haematoma expansion within 72 h after symptom onset developed in 142 (39.9, 95%-CI 34.8–45.0%) of DOAC patients, in 47 (30.3%, 95%-CI 23.1%–37.6%) of VKA patients and in 22 (29.7, 19.3–40.1%) of patients without anticoagulation (Table 3). Non-inferiority of the proportion of patients with haematoma expansion between DOAC and non-anticoagulated patients, as well as between VKA and non-anticoagulated patients was not met (DOAC vs. non-OAC, risk difference 10.2%, 95%-CI -1.4%–21.8%, p = 0.51; VKA vs. non-OAC, risk difference 0.6%, 95%-CI -11.6%–12.8%, p = 0.066, resp.).

Table 3 Radiological characteristics of the ‘haematoma expansion analysis cohort’
Full size table

Factors associated with haematoma expansion

Factors associated with haematoma expansion were analysed in exploratory univariable and multivariable logistic regression models (suppl. Table S4). Longer onset to first brain imaging led to a lower risk of haematoma expansion, while larger baseline haematoma was associated with a higher risk of haematoma expansion. Higher baseline glucose levels increased the risk of haematoma expansion. No such association was found for age, pre-stroke disability, high systolic blood pressure (> 160 mmHg) at admission, concomitant antiplatelet therapy or deep versus lobar location of the ICH (model 1). In model 2 after adjusting for confounders (logits of model 1), no statistically significant association of DOAC vs. non-OAC (adj. OR 1.58, 95% CI 0.13–3.08, p = 0.180) or VKA vs. non-OAC (adj. OR 1.02, 95% CI 0.48–2.21, p = 0.952; two separate models) was found regarding the risk of haematoma expansion.

To estimate the effect of early death a sensitivity for early death was conducted, where all early deaths were counted as substantial haematoma expansion, if no follow-up imaging was available before death. This sensitivity analysis revealed higher risk differences of substantial haematoma expansion between DOAC vs. non-OAC of 13.4% (DOAC rate: 48.4%, non-OAC rate: 35.0%) and the risk difference between VKA vs. non-OAC increases to 6.6% (VKA: 41.6%). Non-inferiority was still not significant for both comparisons. However the adjusted odds ratios for DOAC vs. no-OAC (1.71 (95%-CI: 0.9–3.25) and VKA vs. no-OAC (1.21 (95%-CI: 0.60–2.47)) were similar to those from the original analysis.

Furthermore, a sensitivity analysis on the influence of centre differences revealed similar adjusted odds ratios and, therefore, no influence of the enrolling sites on the primary endpoint was evident.

Effect of anticoagulation reversal in DOAC-ICH

We performed an exploratory analysis of the effect of different methods of anticoagulation reversal in patients treated with DOACs (suppl. Table S5). Of the 356 DOAC-ICH patients, 107 (30.1%) received no antagonization, 212 (59.6%) received 4-factor PCC, and 37 (10.4%) received a specific reversal agent (idarucizumab or andexanet alfa). At baseline, median haematoma volumes were 6.1 mL (IQR 2.1–23.5) in the group without antagonization, 9.7 mL (IQR 4.5–27.5) in the group receiving PCC and 11.3 mL in patients receiving a specific reversal treatment (IQR 2.6–18.0) (p = 0.08). Haematoma expansion developed in 41 patients (38.3% (95%-CI: 29.1–47.5) without antagonization, in 89 (42.0% (95%-CI: 35.4–48.6) receiving PCC and in 12 (32.4% (95%-CI: 17.4–47.5)) receiving a specific reversal agent (p = 0.51).

Effect of anticoagulation reversal in VKA-ICH

Among VKA patients in the ‘HE-cohort’, ICH occurred in 72 (48.3%) within the therapeutic INR range. N = 133 (89%) received PCC in addition to standard treatment with vitamin K. Haematoma expansion occurred in 43 (31.2% (95%-CI: 23.4–38.9)) PCC-patients vs. in 4 (23.5% (95%-CI: 3.4–43.7)) patients with no PCC (p = 0.518). Despite a higher percentage of patients with mRS > 2 at admission in the PCC group, mortality at hospital discharge was similar between groups (suppl. Table S6).

Discussion

The main findings are that: (1) the neurological deficit at hospital admission and the baseline haematoma volume did not differ among non-anticoagulated and anticoagulated ICH patients with AF; (2) the risk of haematoma expansion within 72 h was 10.2% higher in patients taking a DOAC at the time of ICH than in patients not taking an anticoagulant, albeit with overlapping confidence intervals; (3) in a cohort of VKA-ICH with a high proportion of anticoagulation reversal with PCC, the rate of haematoma expansion was similar to that in patients not receiving anticoagulation; (4) No trend towards a beneficial effect of PCC on haematoma expansion was observed in DOAC-ICH; and (5) in hospital and 3-month mortality rates did not differ significantly between patients receiving or not receiving an oral anticoagulant.

Previous studies [15,16,17,18] and systematic reviews with meta-analyses [2, 19] reported controversial findings regarding baseline haematoma size and clinical presentation in OAC-related ICH. In one meta-analysis including 19 studies, baseline haematoma volume was significantly larger in VKA-ICH than in non-anticoagulated patients but VKA patients were significantly older [19]. Data for comparison of DOAC with no anticoagulation were insufficient [19]. A recent analysis of two European national stroke registries reported similar adjusted lower odds of a favourable outcome for VKA and DOAC-associated ICH compared to no oral anticoagulation [20]. Both anticoagulation schemes were also associated with a higher odds of mortality. Mortality at 3-months were similar to our findings for orally anticoagulated patients, but mortality in non-anticoagulated patients differed (30% versus 44% in our population). Reasons could be the lower case-severity at admission (median NIHSS 7 versus 9), as well as the inclusion of early deceased patients and patients not capable to give consent on their own in our study. Table S7 in the supplement summarizes previous studies reporting baseline haematoma volumes or haematoma expansion rates in patients with or without oral anticoagulation. Remarkably, most of the studies that reported imaging data were retrospective or did not include a central imaging analysis. Moreover, the focus of most studies was to compare ICH patients taking a DOAC vs. a VKA rather than comparing them to patients with no anticoagulation although this comparison is best suited to characterize a putative worsening effect of DOACs on haematoma size.

Despite having a large pre-defined non-inferiority margin, our study did not confirm our prespecified hypothesis that DOAC intake at the time of ICH causes a risk of haematoma expansion that is non-inferior compared to no anticoagulation. Instead, 39.9% of patients in the DOAC group compared to 29.7% of non-anticoagulated ICH patients showed HE, albeit with overlapping confidence intervals. The additional multivariate analysis was underpowered but also showed a trend towards an increased risk of haematoma expansion associated with DOAC.

New or increased ventricular extension of the bleeding was observed in 20% of DOAC- compared to 10% in VKA or 14% in non-OAC patients. Although not statistically significant, this difference may be caused by the fact that DOAC affects intrinsic haemostatic mechanisms counteracting secondary haematoma growth [21]. In a healthy brain, dabigatran does not cross the blood–brain barrier, and factor Xa inhibitors are efficiently cleared from the brain by p-glycoprotein efflux pumps [22]. It is speculative as to whether DOAC accumulate with delay after crossing the injured blood–brain barrier.

We did not find a higher proportion of patients with increased haematoma expansion among those taking VKA at the time of ICH compared to non-anticoagulated patients although the majority of VKA patients were effectively anticoagulated based on INR values. This finding contradicts most [23,24,25], but not all, previous studies [26]. A possible explanation is that 89% of our VKA-ICH patients received PCC for acute reversal. In the INCH trial, rapid reversal of the anticoagulatory effect of VKA with PCC prevented haematoma growth compared to slower-acting fresh frozen plasma [27]. Although an effect of reversal on clinical outcome after VKA-ICH has never been firmly established, current American and European guidelines recommend treatment with PCC plus vitamin K [10, 11].

PCC is also used for haemostatic treatment in DOAC-ICH although evidence for its efficacy is limited [10, 11]. Almost 60% of DOAC-ICH patients available for haematoma expansion analysis in our study received PCC. Consistent with previous studies, our exploratory analysis did not suggest that PCC administration lowers the risk of HE [3, 28]. When the specific DOAC reversal agents idarucizumab and andexanet alfa were evaluated in single-arm clinical trials [29, 30], both agents induced rapid reversal of the thrombin inhibitor dabigatran and factor Xa inhibitors, respectively. The recently published ANNEXA-I trial compared andexanet alfa versus standard treatment showed that andexanet alfa was 13% more haemostatically efficacious than standard treatment – 89% of which received PCC [12]. Only 10.4% of DOAC-ICH patients in the present study received a specific reversal agent, precluding any firm conclusions from the numerically lower rate of haematoma expansion observed in patients treated with andexanet alfa or idarucizumab compared to no reversal or administration of PCC.

Our study has several strengths: It was prospective and concurrently recruited patients with DOACs, VKA and no anticoagulation at the time of ICH following a pre-specified algorithm. Only ICH patients with AF were enrolled, improving the homogeneity among groups. Moreover, RASUNOA-prime applied central neuroimaging analysis following a pre-specified protocol and independent analysis by blinded reviewers. Our study also has limitations: Group enrolment was unevenly distributed, showing a predominance of patients who developed ICH while on DOAC resulting from the less frequent prescription of VKA and the less frequent occurrence of ICH in non-anticoagulated patients with AF, respectively. These imbalances may have also been caused by differences in management among centres with a higher awareness for including ICH patients with DOAC. Nearly 50% of patients without follow-up imaging received early palliative care or had already deceased, precluding them from radiologically haematoma expansion analyses and we cannot rule out that the frequency of haematoma expansion in patients without differs from those with follow-up imaging. Furthermore, the unbalanced size of the groups and the limited availability of follow-up imaging led to a reduction in the power of the primary analysis. With the observed sample size, even if the assumptions of the event rates were correct, the power to detect non-inferiority would be 41%. Finally, participation required informed consent by the patient or the patient’s legal representative at some centres, which may have caused selection bias.

Conclusions

In this large prospective study, early haematoma volume and neurological deficit were similar in patients with acute ICH with prior DOAC-treatment compared to no oral anticoagulation. The risk of haematoma expansion in DOAC-ICH was not statistically significantly different compared to patients without anticoagulation.

Availability of data and materials

Anonymized data are available upon reasonable request from the corresponding author.

Abbreviations

CT:

Computer tomography

DOAC:

Direct oral anticoagulant

HE:

Haematoma expansion

ICH:

Intracerebral haemorrhage

MRI:

Magnetic resoncance imaging

PCC:

Prothrombin complex concentrate

VKA:

Vitamin K antagonist

References

  1. Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W., Breithardt, G., Halperin, J. L., Hankey, G. J., Piccini, J. P., et al. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine, 365(10), 883–891.

    Article  PubMed  CAS  Google Scholar 

  2. Tsivgoulis, G., Wilson, D., Katsanos, A. H., Sargento-Freitas, J., Marques-Matos, C., Azevedo, E., Adachi, T., von der Brelie, C., Aizawa, Y., Abe, H., et al. (2018). Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage. Annals of Neurology, 84(5), 694–704.

    Article  PubMed  CAS  Google Scholar 

  3. Purrucker, J. C., Haas, K., Rizos, T., Khan, S., Wolf, M., Hennerici, M. G., Poli, S., Kleinschnitz, C., Steiner, T., Heuschmann, P. U., et al. (2016). Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurology, 73(2), 169–177.

    Article  PubMed  Google Scholar 

  4. Held, C., Hylek, E. M., Alexander, J. H., Hanna, M., Lopes, R. D., Wojdyla, D. M., Thomas, L., Al-Khalidi, H., Alings, M., Xavier, D., et al. (2015). Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: Insights from the ARISTOTLE trial. European Heart Journal, 36(20), 1264–1272.

    Article  PubMed  CAS  Google Scholar 

  5. Hankey, G. J., Stevens, S. R., Piccini, J. P., Lokhnygina, Y., Mahaffey, K. W., Halperin, J. L., Patel, M. R., Breithardt, G., Singer, D. E., Becker, R. C., et al. (2014). Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: The rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke, 45(5), 1304–1312.

    Article  PubMed  CAS  Google Scholar 

  6. Hart, R. G., Diener, H. C., Yang, S., Connolly, S. J., Wallentin, L., Reilly, P. A., Ezekowitz, M. D., & Yusuf, S. (2012). Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: The RE-LY trial. Stroke, 43(6), 1511–1517.

    Article  PubMed  CAS  Google Scholar 

  7. Al-Shahi Salman, R., Frantzias, J., Lee, R. J., Lyden, P. D., Battey, T. W. K., Ayres, A. M., Goldstein, J. N., Mayer, S. A., Steiner, T., Wang, X., et al. (2018). Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: A systematic review and meta-analysis of individual patient data. Lancet Neurology, 17(10), 885–894.

    Article  PubMed  Google Scholar 

  8. Morotti, A., Boulouis, G., Dowlatshahi, D., Li, Q., Shamy, M., Al-Shahi Salman, R., Rosand, J., Cordonnier, C., Goldstein, J. N., & Charidimou, A. (2023). Intracerebral haemorrhage expansion: Definitions, predictors, and prevention. Lancet Neurology, 22(2), 159–171.

    Article  PubMed  Google Scholar 

  9. Dowlatshahi, D., Demchuk, A. M., Flaherty, M. L., Ali, M., Lyden, P. L., Smith, E. E., & Collaboration, V. (2011). Defining hematoma expansion in intracerebral hemorrhage: Relationship with patient outcomes. Neurology, 76(14), 1238–1244.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Christensen, H., Cordonnier, C., Korv, J., Lal, A., Ovesen, C., Purrucker, J. C., Toni, D., & Steiner, T. (2019). European stroke organisation guideline on reversal of oral anticoagulants in acute intracerebral haemorrhage. European Stroke Journal, 4(4), 294–306.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Greenberg, S. M., Ziai, W. C., Cordonnier, C., Dowlatshahi, D., Francis, B., Goldstein, J. N., Hemphill, J. C., 3rd., Johnson, R., Keigher, K. M., Mack, W. J., et al. (2022). 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A guideline from the american heart association/american stroke association. Stroke, 53(7), e282–e361.

    Article  PubMed  CAS  Google Scholar 

  12. Connolly, S. J., Sharma, M., Cohen, A. T., Demchuk, A. M., Czlonkowska, A., Lindgren, A. G., Molina, C. A., Bereczki, D., Toni, D., Seiffge, D. J., et al. (2024). Andexanet for factor Xa inhibitor-associated acute intracerebral hemorrhage. New England Journal of Medicine, 390(19), 1745–1755.

    Article  PubMed  CAS  Google Scholar 

  13. Haas, K., Purrucker, J. C., Rizos, T., Heuschmann, P. U., & Veltkamp, R. (2019). Rationale and design of the registry of acute stroke under novel oral anticoagulants-prime (RASUNOA-prime). European Stroke Journal, 4(2), 181–188.

    Article  PubMed  Google Scholar 

  14. Hinson, H. E., Hanley, D. F., & Ziai, W. C. (2010). Management of intraventricular hemorrhage. Current Neurology and Neuroscience Reports, 10(2), 73–82.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wilson, D., Charidimou, A., Shakeshaft, C., Ambler, G., White, M., Cohen, H., Yousry, T., Al-Shahi Salman, R., Lip, G. Y., Brown, M. M., et al. (2016). Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type. Neurology, 86(4), 360–366.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Wilson, D., Seiffge, D. J., Traenka, C., Basir, G., Purrucker, J. C., Rizos, T., Sobowale, O. A., Sallinen, H., Yeh, S. J., Wu, T. Y., et al. (2017). Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology, 88(18), 1693–1700.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Gerner, S. T., Kuramatsu, J. B., Sembill, J. A., Sprugel, M. I., Hagen, M., Knappe, R. U., Endres, M., Haeusler, K. G., Sobesky, J., Schurig, J., et al. (2019). Characteristics in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Stroke, 50(6), 1392–1402.

    Article  PubMed  CAS  Google Scholar 

  18. Inohara, T., Xian, Y., Liang, L., Matsouaka, R. A., Saver, J. L., Smith, E. E., Schwamm, L. H., Reeves, M. J., Hernandez, A. F., Bhatt, D. L., et al. (2018). Association of intracerebral hemorrhage among patients taking non-vitamin K antagonist vs vitamin K antagonist oral anticoagulants with in-hospital mortality. JAMA, 319(5), 463–473.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Seiffge, D. J., Goeldlin, M. B., Tatlisumak, T., Lyrer, P., Fischer, U., Engelter, S. T., & Werring, D. J. (2019). Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use. Journal of Neurology, 266(12), 3126–3135.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Siepen, B. M., Forfang, E., Branca, M., Drop, B., Mueller, M., Goeldlin, M. B., Katan, M., Michel, P., Cereda, C., Medlin, F., et al. (2024). Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries. Stroke and Vascular Neurology. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/svn-2023-002813

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schlunk, F., Bohm, M., Boulouis, G., Qin, T., Arbel, M., Tamim, I., Fischer, P., Bacskai, B. J., Frosch, M. P., Endres, M., et al. (2019). Secondary bleeding during acute experimental intracerebral hemorrhage. Stroke, 50(5), 1210–1215.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kalus, J. S. (2013). Antithrombotic alternatives for stroke prevention in atrial fibrillation: Critical differences and remaining questions. Drugs Context, 2013, 212251.

    PubMed  PubMed Central  Google Scholar 

  23. Cucchiara, B., Messe, S., Sansing, L., Kasner, S., Lyden, P., & Investigators, C. (2008). Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke, 39(11), 2993–2996.

    Article  PubMed  CAS  Google Scholar 

  24. Huhtakangas, J., Tetri, S., Juvela, S., Saloheimo, P., Bode, M. K., & Hillbom, M. (2011). Effect of increased warfarin use on warfarin-related cerebral hemorrhage: A longitudinal population-based study. Stroke, 42(9), 2431–2435.

    Article  PubMed  CAS  Google Scholar 

  25. Horstmann, S., Rizos, T., Lauseker, M., Mohlenbruch, M., Jenetzky, E., Hacke, W., Steiner, T., & Veltkamp, R. (2013). Intracerebral hemorrhage during anticoagulation with vitamin K antagonists: A consecutive observational study. Journal of Neurology, 260(8), 2046–2051.

    Article  PubMed  CAS  Google Scholar 

  26. Flaherty, M. L., Tao, H., Haverbusch, M., Sekar, P., Kleindorfer, D., Kissela, B., Khatri, P., Stettler, B., Adeoye, O., Moomaw, C. J., et al. (2008). Warfarin use leads to larger intracerebral hematomas. Neurology, 71(14), 1084–1089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Steiner, T., Poli, S., Griebe, M., Husing, J., Hajda, J., Freiberger, A., Bendszus, M., Bosel, J., Christensen, H., Dohmen, C., et al. (2016). Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): A randomised trial. Lancet Neurology, 15(6), 566–573.

    Article  PubMed  CAS  Google Scholar 

  28. Gerner, S. T., Kuramatsu, J. B., Sembill, J. A., Sprugel, M. I., Endres, M., Haeusler, K. G., Vajkoczy, P., Ringleb, P. A., Purrucker, J., Rizos, T., et al. (2018). Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Annals of Neurology, 83(1), 186–196.

    Article  PubMed  CAS  Google Scholar 

  29. Pollack, C. V., Jr., Reilly, P. A., van Ryn, J., Eikelboom, J. W., Glund, S., Bernstein, R. A., Dubiel, R., Huisman, M. V., Hylek, E. M., Kam, C. W., et al. (2017). Idarucizumab for dabigatran reversal - full cohort analysis. New England Journal of Medicine, 377(5), 431–441.

    Article  PubMed  CAS  Google Scholar 

  30. Connolly, S. J., Crowther, M., Eikelboom, J. W., Gibson, C. M., Curnutte, J. T., Lawrence, J. H., Yue, P., Bronson, M. D., Lu, G., Conley, P. B., et al. (2019). Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. New England Journal of Medicine, 380(14), 1326–1335.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank all RASUNOA-prime collaborators, including participating centres, heads of departments, local physicians, radiologists and study nurses for their support during the study. Further collaborators for the RASUNOA prime ICH substudy: Heidelberg University Hospital: Solveig Horstmann, Alexandra KrauR, Caroline Renninger, Peter Ringleb. University Hospital Aachen: Arno Reich. SLK-Klinken Heilbronn: Eve Kohler. University Hospital Frankfurt a. M.: Erendira Boss, Jan Hendrik Schaefer. Johannes Wesling Klinikum Minden: Marc Pflug .University Medicine Greifswald: Bettina von Sarnowski. Hannover Medical School: Gerrit Maximilian GroRe, Johanna Ernst, Karin WeiRenborn, Ramona Schupper, Hans Worthmann. University Hospital Schleswig-Holstein, Lubeck: Susanne Riebau. Vivantes Klinikum Neukolln Berlin: Olaf Crome, Boris Dimitrijeski, Jens Offermann. Charite Berlin, Department for Neurology with experimental Neurology and Center for Stroke Research Berlin (CSB): Ida Rangus. Klinikum Stuttgart: Elisabeth Schmid. University Hospital Tubingen: Khouloud Poli, Johannes Tunnerhoff. University Hospital Leipzig: Dominik Michalski, Johann O. Pelz. University Hospital GieRen: Martin Juenemann, Tobias Braun. Martin-Luther-University of Halle-Wittenberg: Tobias J. Muller, Katja Wartenberg. University Hospital Schleswig-Holstein, Kiel: Andreas Binder, Johannes Meyne. Klinikum Rechts der Isar, Munchen: Benno Ikenberg, Johanna Hartl. Herz-Jesu-Hospital Hiltrup, Munster: Michael Ohms, Sebasitan Edelbusch. University Hospital Mannheim: Marc Fatar, Angelika Alonso. Klinikum Nurnberg-Sud, Paracelsis Medical Clinic, Nurnberg: Martin Nuckel, Frank Erbguth. University Hospital Wurzburg: Alexandra Grau, Udo Selig. University Hospital Munster: Rainer Dziewas, Jens Minnerup. University Hospital Dresden: Kristian Barlinn, Kathrin Haase. University Hospital Hamburg-Eppendorf, Hamburg: Gotz Thomalla, Milani Deb-Chatterji. Juliusspital Wurzburg: Mathias Maurer, Mathias Pfau. Asklepios Klinik Altona, Hamburg: Peter Michels, Zoran Vukovic. University Hospital Mainz: Timo Uphaus, Klaus Groschel, Sonja Groschel, Marianne Hahn. Leopoldina-Krankenhaus Schweinfurth: Joannes Muhler, Klaus Dotter. Helios Dr. Horst Schmidt Kliniken Wiesbaden: Michaela Wagner-Heck, Frank Arne Wollenweber. University Hospital Dusseldorf: Sebastian Jander, John-Ih Lee. Evangelisches Krankenhaus Bielefeld: Wolf-Rudiger Schabitz, Inken Piehl. Krankenhaus der Barmherzigen Bruder Eisenstadt, Austria: Michael Frattner, Dimitre Staykov. Klinikum Ludwigshafen: Christian Urbanek, Sabine Schroder. Evangelisches Klinikum Herne: Sylke Dullberg-Boden. Nordwest-Krankenhaus Sanderbusch: Pawel Kermer, Matthias Kaste. Asklepios Klinik Wandsbek, Hamburg: Lars Marquardt, Haiko Kazarians. Universitatsklinikum Essen: Christoph Kleinschnitz, Peter Kraft. Martha-Maria Hospital Halle: Frank Hoffmann, Andrea Kraft. Asklepios Fachklinik Teupitz: Jurgen Hartmut Faiss. Klinikum Dortmund: Gernot Reimann, Michael Schwarz. Frankfurt Hoechst, Frankfurt a. M.: Thorsten Steiner. University Hospital Jena: Albrecht Gunther. Hospital Nordwest, Frankfurt a. M.: Uta Meyding Lamade, Matthias W. Lorenz

Funding

Open Access funding enabled and organized by Projekt DEAL. This study was an investigator-initiated study with commercial funding by an unrestricted research grant to the Heidelberg University Hospital, Germany. Supported by unrestricted research grants from Bayer Vital GmbH Germany, Bristol-Myers Squibb/Pfizer Alliance, Boehringer Ingelheim Pharma GmbH&Co.KG and Daiichi Sankyo Europe GmbH. The funding sources had no influence on the design of the study, the data analysis, the draft of the manuscript or the decision to submit the manuscript. The authors had full access to all data and had final responsibility for the decision to submit for publication.

Author information

Author notes

  1. Roland Veltkamp, Kirsten Haas, Peter U. Heuschmann and Jan C. Purrucker have contributed equally to this work.

Authors and Affiliations

  1. Department of Brain Sciences, Imperial College London, London, UK

    Roland Veltkamp

  2. Department of Neurology, Alfried-Krupp Hospital, Essen, Germany

    Roland Veltkamp, Adrian Heeger, David Kinzler, Patrick Müller & Pascal Rappard

  3. Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany

    Roland Veltkamp, Timolaos Rizos & Jan C. Purrucker

  4. Institute of Clinical Epidemiology and Biometry, Julius-Maximilians-Universität Würzburg (JMU), Würzburg, Germany

    Kirsten Haas, Viktoria Rücker, Marilen Sieber & Peter U. Heuschmann

  5. Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany

    Uwe Malzahn

  6. Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany

    Johannes Schiefer

  7. Department of Neurology, SLK-Kliniken Heilbronn, Heilbronn, Germany

    Christian Opherk

  8. Department of Neurology, University Hospital Frankfurt, Goethe-University, Frankfurt Am Main, Germany

    Waltraud Pfeilschifter

  9. Department of Neurology, Klinikum Lüneburg, Lüneburg, Germany

    Waltraud Pfeilschifter

  10. Department of Neurology, University Hospital Ulm, Ulm, Germany

    Katharina Althaus

  11. Department of Neurology and Neurogeriatrics, Johannes Wesling University Hospital Minden, Minden, Germany

    Peter Schellinger

  12. Universitätsklinikum Ruhr-Universität Bochum, Bochum, Germany

    Peter Schellinger

  13. Department of Neurology, University Medicine Greifswald, Greifswald, Germany

    Bernadette Gaida

  14. Department of Neurology, Hannover Medical School, Hannover, Germany

    Maria Magdalena Gabriel

  15. Neurovascular Center, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

    Georg Royl

  16. Vivantes Klinikum Neukölln, Berlin, Germany

    Darius G. Nabavi

  17. Department of Neurology, Universitätsklinikum Würzburg (UKW), Würzburg, Germany

    Karl Georg Haeusler

  18. Center for Stroke Research Berlin (CSB), Berlin, Germany

    Christian H. Nolte

  19. Department of Neurology With Experimental Neurology, Berlin Institute of Health (BIH), Charité Universitätsmedizin Berlin, Berlin, Germany

    Christian H. Nolte

  20. Department of Neurology, Klinikum Stuttgart, Stuttgart, Germany

    Marc E. Wolf

  21. Department of Neurology & Stroke, Tübingen University Hospital, Tübingen, Germany

    Sven Poli

  22. Hertie Institute for Clinical Brain Research, Tübingen University Hospital, Tübingen, Germany

    Sven Poli

  23. Department of Neuroradiology, Toronto Western Hospital Division of Neuroradiology, Toronto, Canada

    Pascal Mosimann

  24. Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany

    Peter U. Heuschmann

  25. Institute for Medical Data Science, University Hospital Würzburg, Würzburg, Germany

    Peter U. Heuschmann

Authors
  1. Roland Veltkamp
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Kirsten Haas
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Viktoria Rücker
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Uwe Malzahn
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Adrian Heeger
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. David Kinzler
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Patrick Müller
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Pascal Rappard
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Timolaos Rizos
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Johannes Schiefer
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Christian Opherk
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Waltraud Pfeilschifter
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Katharina Althaus
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Peter Schellinger
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Bernadette Gaida
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Maria Magdalena Gabriel
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Georg Royl
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Darius G. Nabavi
    View author publications

    You can also search for this author inPubMed Google Scholar

  19. Karl Georg Haeusler
    View author publications

    You can also search for this author inPubMed Google Scholar

  20. Christian H. Nolte
    View author publications

    You can also search for this author inPubMed Google Scholar

  21. Marc E. Wolf
    View author publications

    You can also search for this author inPubMed Google Scholar

  22. Sven Poli
    View author publications

    You can also search for this author inPubMed Google Scholar

  23. Marilen Sieber
    View author publications

    You can also search for this author inPubMed Google Scholar

  24. Pascal Mosimann
    View author publications

    You can also search for this author inPubMed Google Scholar

  25. Peter U. Heuschmann
    View author publications

    You can also search for this author inPubMed Google Scholar

  26. Jan C. Purrucker
    View author publications

    You can also search for this author inPubMed Google Scholar

Consortia

on behalf of the RASUNOA-prime investigators

  • Solveig Horstmann
  • , Alexandra Krauß
  • , Caroline Renninger
  • , Peter Ringleb
  • , Arno Reich
  • , Eve Kohler
  • , Erendira Boss
  • , Jan Hendrik Schaefer
  • , Marc Pflug
  • , Bettina von Sarnowski
  • , Gerrit Maximilian Große
  • , Johanna Ernst
  • , Karin Weißenborn
  • , Ramona Schupper
  • , Hans Worthmann
  • , Susanne Riebau
  • , Olaf Crome
  • , Boris Dimitrijeski
  • , Jens Offermann
  • , Ida Rangus
  • , Elisabeth Schmid
  • , Khouloud Poli
  • , Johannes Tünnerhoff
  • , Dominik Michalski
  • , Johann O. Pelz
  • , Martin Juenemann
  • , Tobias BraunTobias J. Müller
  • , Katja Wartenberg
  • , Andreas Binder
  • , Johannes Meyne
  • , Benno Ikenberg
  • , Johanna Härtl
  • , Michael Ohms
  • , Sebasitan Edelbusch
  • , Marc Fatar
  • , Angelika Alonso
  • , Martin Nückel
  • , Frank Erbguth
  • , Alexandra Grau
  • , Udo Selig
  • , Rainer Dziewas
  • , Jens Minnerup
  • , Kristian Barlinn
  • , Kathrin Haase
  • , Götz Thomalla
  • , Milani Deb-Chatterji
  • , Mathias Mäurer
  • , Mathias Pfau
  • , Peter Michels
  • , Zoran Vukovic
  • , Timo Uphaus
  • , Klaus Gröschel
  • , Sonja Gröschel
  • , Marianne Hahn
  • , Joannes Mühler
  • , Klaus Dötter
  • , Michaela Wagner-Heck
  • , Frank Arne Wollenweber
  • , Sebastian Jander
  • , John-Ih Lee
  • , Wolf-Rüdiger Schäbitz
  • , Inken Piehl
  • , Michael Frattner
  • , Dimitre Staykov
  • , Christian Urbanek
  • , Sabine Schröder
  • , Sylke Düllberg-Boden
  • , Pawel Kermer
  • , Matthias Kaste
  • , Lars Marquardt
  • , Haiko Kazarians
  • , Christoph Kleinschnitz
  • , Peter Kraft
  • , Frank Hoffmann
  • , Andrea Kraft
  • , Jürgen Hartmut Faiss
  • , Gernot Reimann
  • , Michael Schwarz
  • , Thorsten Steiner
  • , Albrecht Günther
  • , Uta Meyding Lamadé
  •  & Matthias W. Lorenz

Contributions

RV initiated and conceived the study; the protocol was written by RV, JP, TR, KH, UM, and PUH. RV, JP, KH, VR, and PUH analysed the data. MS helped with data curation. AH, DK, PM, PR, and JP performed the radiological analyses. VR, UM, KH, and PUH performed stastistical data analysis and interpretation. RV and JP drafted the manuscript, which was critically revised by all authors. RV, TR, JS, CO, WP, KA, PS, BG, MMG, GR, DGN, KGH, CN, MEW, SP, JP and all authors listed in the appendix were local principal investigators.

Corresponding author

Correspondence to Roland Veltkamp.

Ethics declarations

Ethics approval and consent to participate

The ethics committee of the Medical Faculty of the University Heidelberg as well as all local ethics committees approved the study protocol (S-088/2015). Patients were eligible for the study if they were 18 years or older and either the patient or a legal representative had provided consent. Informed consent could be waived if patients were not able to consent and died before a legal representative could be installed.

Consent for publication

Not applicable.

Competing interests

RV is an investigator of the NIHR Imperial Biomedical Research Centre and reports fees for consulting and speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Daichi Sankyo, Portola, Biogen, Medtronic, and Morphosys; and research grants from Bayer, Boehringer, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, and Medtronic (ODEA study), outside of the submitted work. TR received consulting honoraria, speakers’ honoraria and travel support from BMS Pfizer, Boehringer Ingelheim, Bayer HealthCare and Daiichi Sankyo, outside the submitted work. WP received consulting honoraria, speakers’ honoraria and travel support from Alexion, Boehringer Ingelheim, Bayer HealthCare and Daiichi Sankyo, outside the submitted work. KA has received lecture fees from Boehringer Ingelheim, Daiichi Sankyo, Alexion and BMS/Pfizer, outside the submitted work. PS received honoraria from Astra Zeneca, Boehringer Ingelheim, Biogen, Daiichi, Amgen, Merck and participated on advisory boards for Boehringer Ingelheim and Astra Zeneca. BG has received speaking honoraria and travel expenses from Bayer Vital GmbH, Boehringer Ingelheim Pharma GmbH & Co.KG, Daiichi Sankyo Deutschland GmbH, UCB Pharma GmbH, UNEEG medical DE GmbH and BMS/Pfizer Alliance, outside the submitted work. GR has received consultation fees and travel expenses from Bayer, Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Astra Zeneca, Novartis and Cardinal Health, outside the submitted work. DGN has received speaker honoraria, consultation fees and travel expenses from Astra Zeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi, outside the submitted work. KGH reports speaker´s honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Alexion, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates. CHN received research grants from the German Ministry of Research and Education, German Center for Neurodegenerative Diseases, German Center for Cardiovascular Research, and speaker and/or consultation fees from Abbott, Alexion, Astra Zeneca, Bayer Pharma, Bristol-Myers Squibb, Daiichi Sankyo, Novartis, Pfizer Pharma, Portola and Takeda, all outside the submitted work. MEW has received honoraria for lectures from Daiichi Sankyo, BMS/Pfizer and Sanofi. SP has received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). PUH reports grants from the German Ministry of Research and Education, European Union, German Parkinson Society, University Hospital Würzburg, the German Heart Foundation, Federal Joint Committee within the Innovationfond, German Research Foundation, Bavarian State, German Cancer Aid, Charité–Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), Bristol-Myers Squibb, Boehringer-Ingelheim, and Daiichi Sankyo), outside the submitted work. JP has received consultation fees and travel expenses from Abbott, Akcea, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer, outside the submitted work. All other authors: none.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Veltkamp, R., Haas, K., Rücker, V. et al. Association of oral anticoagulants with risk of brain haemorrhage expansion compared to no-anticoagulation. Neurol. Res. Pract. 7, 12 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s42466-024-00358-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s42466-024-00358-9

Neurological Research and Practice

ISSN: 2524-3489

Contact us