Are antiplatelets and anticoagulants safe and beneficial in people with cavernomas?

Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis.

Zuurbier SM, Hickman CR, Tolias CS, et al; Scottish Audit of Intracranial Vascular Malformations Steering Committee.

Lancet Neurol 2019; 18:935-941.



Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations.


In this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999-2003 or 2006-10. We compared the association between use of antithrombotic therapy after first presentation and the occurrence of intracranial haemorrhage or persistent or progressive focal neurological deficit due to the cerebral cavernous malformations during up to 15 years of prospective follow-up with multivariable Cox proportional hazards regression assessed in all individuals identified in the database. We also did a systematic review and meta-analysis, in which we searched Ovid MEDLINE and Embase from database inception to Feb 1, 2019, to identify comparative studies to calculate the intracranial haemorrhage incidence rate ratio according to antithrombotic therapy use. We then generated a pooled estimate using the inverse variance method and a random effects model.


We assessed 300 of 306 individuals with a cerebral cavernous malformation who were eligible for study. 61 used antithrombotic therapy (ten [16%] of 61 used anticoagulation) for a mean duration of 7·4 years (SD 5·4) during follow-up. Antithrombotic therapy use was associated with a lower risk of subsequent intracranial haemorrhage or focal neurological deficit (one [2%] of 61 vs 29 [12%] of 239, adjusted hazard ratio [HR] 0·12, 95% CI 0·02-0·88; p=0·037). In a meta-analysis of six cohort studies including 1342 patients, antithrombotic therapy use was associated with a lower risk of intracranial haemorrhage (eight [3%] of 253 vs 152 [14%] of 1089; incidence rate ratio 0·25, 95% CI 0·13-0·51; p<0·0001; I2=0%).


Antithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial.


See also

Bervini D, Jaeggi C, Mordasini P, Schucht P, Raabe A. Antithrombotic medication and bleeding risk in patients with cerebral cavernous malformations: a cohort study. J Neurosurg 2018; doi: 10.3171/2018.1.JNS172547 (Epub ahead of print).

Both papers are cited in the neurochecklist:

Cerebral cavernous malformations (cavernomas): clinical features

Abstract link 1

Abstract link 2

By Karlo J Lizarraga and Antonio AF De Salles –, CC BY 2.5, Link

What MRI features predict anticoagulant-induced intracerebral haemorrhage?

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation.

Martí-Fàbregas J, Medrano-Martorell S, Merino E, et al; HERO study investigators

Neurology 2019; 92:e2432-e2443.



We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.


Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.


We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4).


Patients taking oral antocoagulants who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of intracerebral haemorrhage. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.

This paper is cited in the neurochecklist:

Intracerebral haemorrhage (ICH): causes and risk factors 

Abstract link

Internet Archive Book Images on Flickr.
Neurochecklists updates

40 very handy and practical neurochecklists

Neurochecklists now contains >2000 checklists on all aspects of neurology.
Many checklists come to the rescue only to fill a knowledge gap.
By Samurai Gandhi - Own work, CC BY-SA 4.0, Link
By Samurai GandhiOwn work, CC BY-SA 4.0, Link
Most neurochecklists however address important practical questions or outline pragmatic steps in managing neurological disorders.
House of Knowledge. Ian Parkes on Flikr.
House of Knowledge. Ian Parkes on Flikr.
To illustrate, below is a selection of 40 handy neurochecklists


Anticoagulants: bridging therapy for surgery
Antiepileptic drugs (AEDs): choice with medical conditions
Apomorphine test
Cluster headache (CH): chronic prophylaxis
Cerebral vein thrombosis (CVT): investigations


Dementia: safety and driving risks
Diaphragmatic paralysis: neurological causes
Drug induced Parkinsonism: risk factors and causes
Epilepsy: patient information
Essential tremor (ET): drug treatment


Falls: management
Genetic counselling
HyperCKaemia: neurological causes
Lumbar puncture (LP): indications and precautions
Lyme Neuroborreliosis: management


Migraine prophylaxis: drugs
Mitochondrial diseases: investigations
Motor neurone disease (MND): supportive care
Multiple sclerosis (MS): general investigations
Pregnancy and myasthenia gravis (MG): management


Myelopathy with normal MRI
Myotonic dystrophy type 1: assessments and monitoring
Neurological complications of liver transplantation
Neurosarcoidosis: treatment
Neurosyphilis: clinical features


Peripheral neuropathy (PN): red flags for ominous causes
Pineal cysts: monitoring
Psychogenic seizures: management
Subarachnoid haemorrhage (SAH): complications
Sudden unexpected death in epilepsy (SUDEP): management


Syncope: red flags for admission
Thrombolysis: bleeding risk prediction tools
Trigeminal neuralgia (TN): management
Tic disorders: differential diagnosis and management
Passive tilt table test: indications and contraindications


Transient loss of consciousness (TLOC): assessment
Vitamin B12 deficiency: tests of B12 metabolites 
Warfarin: switching to new oral anticoagulants
Wernicke’s encephalopathy: risks and clinical features
Young onset dementia


Explore these and many other practical checklists on Neurochecklists

By Ansonlobo - Own work, CC BY-SA 4.0, Link
By AnsonloboOwn work, CC BY-SA 4.0, Link