Brain microbleeds, anticoagulation, and hemorrhage risk

Charidimou, Andreas; Karayiannis, Christopher; Song, Tae‐Jin; Örken, Dilek Neci̇oğlu; Thijs, Vincent; Lemmens, Robin; Kim, Jinkwon; Goh, Su Mei; Phan, Thanh G.; Soufan, Cathy; Chandra, Ronil V.; Slater, Lee-Anne; Haji, Shamir; Mok, Vincent; Horstmann, Solveig; Leung, Kam Tat; Kawamura, Y.; Sato, Nobuyuki; Hasebe, Naoyuki; Saito, Tsukasa; Wong, Ka Sing; Soo, Yannie; Veltkamp, Roland; Flemming, Kelly D.; Imaizumi, Toshio; Srikanth, Velandai; Heo, Ji Hoe

doi:10.1212/wnl.0000000000004704

Cited by 102 publications

(72 citation statements)

References 40 publications

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“…Our results are in line with findings from a recent meta-analysis, which aggregated data from cohorts with other study objectives that included patients with ischaemic stroke with AF treated with warfarin or DOACs. In this meta-analysis (n=1552), patients with ≥5 CMBs were also associated with a higher risk of ICH (OR 5.5, 95% CI 2.07 to 14.66) 26. Furthermore, our study provides additional data about the influence of INR on risk of ICH.…”

Section: Discussionmentioning

confidence: 58%

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study

Soo

Abrigo

Leung

et al. 2018

J Neurol Neurosurg Psychiatry

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Background and purposeCerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs.MethodsIn this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs.ResultsA total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH.ConclusionsIn Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

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Section: Discussionmentioning

confidence: 58%

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study

Soo

Abrigo

Leung

et al. 2018

J Neurol Neurosurg Psychiatry

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“…There was no difference between VKA-and NOAC-ICH (52% vs. 48%; P = 0.763; Table 1). However, the median CMB number was significantly lower in NOAC-ICH patients (2 [1-3] vs. 7 [4][5][6][7][8][9][10][11]; P < 0.001 (Table 1 and Fig. 1).…”

Section: Resultsmentioning

confidence: 97%

“…Multivariable logistic regression analyses were performed on the association of baseline characteristics with the presence of five or more cerebral microbleeds in baseline neuroimaging. 11 In univariable models of all baseline characteristics a threshold of P < 0.1 was used to identify candidate variables for inclusion in the multivariate regression models that tested statistical significance hypothesis using the likelihood ratio test with an alpha value of 0.05. We also performed sensitivity univariable/ multivariable logistic regression analyses after excluding patients with no presence of cerebral microbleeds on baseline neuroimaging.…”

Section: Statistical Analysesmentioning

confidence: 99%

Microbleed prevalence and burden in anticoagulant‐associated intracerebral bleed

Lioutas

Goyal

Katsanos

et al. 2019

Ann Clin Transl Neurol

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Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation‐related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA‐ICH, 48% in NOAC‐ICH). NOAC‐ICH patients had lower median CMB count [2(IQR:1–3) vs. 7(4–11); P < 0.001]; ≥5 CMBs were less prevalent in NOAC‐ICH (4% vs. 31%, P = 0.006). This inverse association between NOAC exposure and high CMB count persisted in multivariable logistic regression models adjusting for potential confounders (OR 0.10, 95%CI: 0.01–0.83; P = 0.034).

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“…Follow-up MRI examinations were available for 56 patients with a median time after first postinterventional scan of 6 months (interquartile range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In 91.1% (51/56) of those, there was no further increase in SWI lesions (Figure 2).…”

Section: Further Follow-up Mri Scansmentioning

confidence: 99%

“…Hence, in such patients there is a therapeutic balancing act between the risk of ischemic stroke and ICH. Additionally, CMBs are increasingly considered in guiding treatment decisions for intravenous thrombolysis 17 or anticoagulation, 18 and such treatments might be withheld from patients with aHV because of the presence of SWI lesions. It is therefore important to know whether multiple SWI lesions in patients with aHV are true CMBs suggesting increased ICH risk or simply an epiphenomenon caused by either the material or the intracardiac procedure.…”

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confidence: 99%

Prevalence and Evolution of Susceptibility‐Weighted Imaging Lesions in Patients With Artificial Heart Valves

Breiding

Duerrenmatt

Meinel

et al. 2019

JAHA

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BackgroundIn patients with mechanical heart valves, cerebral susceptibility‐weighted imaging (SWI) lesions on magnetic resonance imaging, postulated to be caused by degenerative metallic abrasion, are frequently referred to as valve abrasion. It remains unclear whether valve implantation not requiring cardiopulmonary bypass or biological heart valves also shows those lesions.Methods and ResultsTwo blinded readers rated SWI lesions and cerebral amyloid angiopathy probability according to established criteria on brain magnetic resonance imaging pre‐ and postinterventionally. We assessed the association between valve type/cardiopulmonary bypass use and SWI lesion count on the first postinterventional scan using multivariable logistic regression. On postinterventional magnetic resonance imaging, 57/58 (98%) patients with mechanical heart valves had at least 1 and 46/58 (79%) 3 or more SWI lesions, while 92/97 (95%) patients with biological heart valves had at least 1 and 72/97 (74%) 3 or more SWI lesions. On multivariate analysis, duration of cardiopulmonary bypass during implantation significantly increased the odds of having SWI lesions on the first postinterventional magnetic resonance imaging (β per 10 minutes 0.498; 95% CI, 0.116–0.880; P=0.011), whereas valve type showed no significant association (P=0.338). Thirty‐seven of 155 (23.9%) patients fulfilled the criteria of possible/probable cerebral amyloid angiopathy.Conclusions SWI lesions in patients with artificial heart valves evolve around the time point of valve implantation and the majority of patients had multiple lesions. The missing association with the valve type weakens the hypothesis of degenerative metallic abrasion and highlights cardiopulmonary bypass as the main risk factor for SWI occurrence. SWI lesions associated with cardiac procedures can mimic cerebral amyloid angiopathy. Further research needs to clarify whether those lesions are associated with intracranial hemorrhage after intravenous thrombolysis or anticoagulation.

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Brain microbleeds, anticoagulation, and hemorrhage risk

Cited by 102 publications

References 40 publications

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study

Microbleed prevalence and burden in anticoagulant‐associated intracerebral bleed

Prevalence and Evolution of Susceptibility‐Weighted Imaging Lesions in Patients With Artificial Heart Valves

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