What are the causes of recurrent hemorrhagic strokes?

From the Guidelines

Multiple episodes of hemorrhagic strokes are primarily caused by uncontrolled hypertension, which damages blood vessel walls over time, as well as cerebral amyloid angiopathy, particularly in older adults. Other significant causes include anticoagulant medications (like warfarin, heparin, or DOACs) 1, blood disorders (such as thrombocytopenia or hemophilia), illicit drug use (especially cocaine and methamphetamine), and cerebral vascular malformations (including aneurysms, arteriovenous malformations, and cavernomas). Underlying conditions like liver disease, kidney failure, and brain tumors can also contribute to recurrent bleeding. Genetic disorders such as CADASIL or Moyamoya disease increase risk in some patients.

Key Risk Factors

• Uncontrolled hypertension: damages blood vessel walls over time, increasing the risk of recurrent hemorrhage 1
• Cerebral amyloid angiopathy: particularly in older adults, associated with lobar location of the initial ICH 1
• Anticoagulant medications: increase the risk of recurrence, especially in patients with a history of lobar ICH 1
• Blood disorders: such as thrombocytopenia or hemophilia, increase the risk of recurrent bleeding
• Illicit drug use: especially cocaine and methamphetamine, can cause blood vessel damage and increase the risk of hemorrhage
• Cerebral vascular malformations: including aneurysms, arteriovenous malformations, and cavernomas, can increase the risk of recurrent bleeding

Prevention and Management

Prevention focuses on strict blood pressure control, targeting below 130/80 mmHg 1, careful management of anticoagulation therapy, avoiding recreational drugs, treating underlying conditions, and regular neuroimaging follow-up for those with known vascular abnormalities. Lifestyle modifications including limiting alcohol consumption, smoking cessation, maintaining healthy weight, and regular exercise are also essential for reducing recurrence risk. The recent study by Anderson et al. 1 highlights the importance of blood pressure management after intracerebral and subarachnoid hemorrhage, and the need for further research to determine the optimal approach to blood pressure lowering in these conditions.

From the FDA Drug Label

In a post-hoc analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial where 2,365 adult patients, without CHD who had a stroke or TIA within the preceding 6 months, were treated with atorvastatin calcium 80 mg, a higher incidence of hemorrhagic stroke was seen in the atorvastatin calcium 80 mg group compared to placebo (55,2.3% atorvastatin calcium vs. 33,1.4% placebo; HR: 1.68,95% CI: 1.09,2.59; p=0. 0168). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the atorvastatin calcium group

The causes of multiple episodes of hemorrhagic strokes are not explicitly stated in the provided text, but baseline characteristics, including hemorrhagic and lacunar stroke on study entry, may be associated with a higher incidence of hemorrhagic stroke in patients taking atorvastatin calcium 80 mg 2.

• Hemorrhagic stroke on study entry may be a contributing factor.
• Lacunar stroke on study entry may also be a contributing factor. However, the text does not provide a clear answer to the question of what causes multiple episodes of hemorrhagic strokes.

From the Research

Causes of Multiple Episodes of Hemorrhagic Strokes

• Hypertension is a major modifiable risk factor for stroke, including hemorrhagic stroke, as stated in 3
• Intracerebral haemorrhage can be caused by deep perforator (hypertensive) arteriopathy, cerebral amyloid angiopathy, or arteriolosclerosis, as mentioned in 3
• Macrovascular lesions, such as vascular malformations, aneurysms, and cavernomas, can also cause intracerebral haemorrhage, particularly in younger patients, as noted in 3
• Hemorrhagic transformation (HT) is a serious complication of acute ischemic stroke, and risk factors for HT include demographic factors, comorbidities, and predictors such as higher NIHSS score and larger infarction size, as discussed in 4
• Genetic factors, such as somatic mutations in the RAS/MAPK and MAPK/ERK pathways, can contribute to the development of brain arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms, which are major causes of hemorrhagic stroke, as highlighted in 5
• Female-specific factors, such as pregnancy, eclampsia or pre-eclampsia, postmenopausal status, and hormone therapy, can influence a woman's long-term risk of hemorrhagic stroke, as mentioned in 6

Risk Factors for Hemorrhagic Stroke

• Essential hypertension, atrial fibrillation, diabetes mellitus, congestive heart failure, and ischemic heart disease are comorbidities that can increase the risk of hemorrhagic stroke, as discussed in 4
• Higher plasma glucose levels, higher body temperature during ischemic event, and lower low-density lipoprotein and total cholesterol can also increase the risk of hemorrhagic transformation, as noted in 4
• Systemic complications, such as cardiac and respiratory problems, can occur after ischemic and hemorrhagic strokes and have a major impact on patient outcomes, as stated in 7

Clinical Features of Hemorrhagic Stroke

• Hemorrhagic stroke can present with severe symptoms, including sudden onset of headache, vomiting, and loss of consciousness, as mentioned in 3
• The presence of intracranial aneurysms, arteriovenous malformations, or cavernous malformations can pose unique clinical dilemmas during pregnancy and delivery, as discussed in 6
• Women with vascular malformations may require multidisciplinary care to assess the risks and benefits of delivery methods, as noted in 6