High Burden of Brain Microbleed May Up tPA Bleeding Risk

I would think the solution to this is reduce the size of the bolus substantially and direct the tPA directly to the clot. I could see no solution that was presented to fix this problem. Don't just tell me there is a problem, suggest a solution. What a waste of research dollars otrherwise.

Magnetic nanoparticles could stop blood clot-caused strokes

High Burden of Brain Microbleed May Up tPA Bleeding Risk

Stroke patients with cerebral microbleeds had a twofold greater risk for intracerebral hemorrhage following intravenous thrombolysis (tPA), and bleeding risk increased by as much as 12-fold among patients with the highest (>10) microbleed burden, according to a meta-analysis.
The risk of symptomatic brain bleeds after treatment was found to be higher in patients with evidence of cerebral microbleeds compared with patients without cerebral microbleeds (risk ratio 2.36, 95% CI 1.21-4.61, P=0.01), reported Georgios Tsivgoulis, MD, of the University of Athens School of Medicine in Greece, and colleagues
Nine studies were included in the analysis, which showed high cerebral microbleed (CMB) burden, identified through MRI, to be a significant independent risk factor for symptomatic brain bleeds in stroke patients treated with tPA, they wrote in JAMA Neurology.
The findings suggest that pre-treatment MRI assessment of cerebral microbleed burden can serve as an independent predictor of brain bleeding risk in ischemic stroke patients receiving tPA, the authors wrote.
They added that the reliance on CT scans, and not MRI, for patient assessment in the stroke emergency care setting remains a significant challenge to identifying cerebral microbleed burden.
While cerebral microbleeds are considered an independent predictor of higher cerebral bleeding risk, earlier studies assessing their clinical impact on brain bleed risk in stroke patients treated with tPA have been mixed and many have not assessed the impact of cerebral microbleed burden, the researchers noted.
"The potential association of CMB presence with the risk of symptomatic intracerebral hemorrhage in patients with acute ischemic stroke treated with intravenous thrombolysis remains controversial," they wrote.
In an effort to better understand the impact of a high cerebral microbleed burden detected by MRI scan prior to tPA treatment on symptomatic intracerebral hemorrhage risk in the ischemic stroke setting, the researchers analyzed studies reporting intracerebral bleeding rates in ischemic stroke patients with known pre-tPA cerebral microbleed burden.
The meta-analysis, which included a total of 2,479 patients, confirmed a higher risk for symptomatic brain bleeds following treatment with tPA in patients with a cerebral microbleed burden of more than 10, compared with patients with zero to 10 cerebral microbleeds or one to 10 cerebral microbleeds on pretreatment MRI.
The authors also reported a higher risk for symptomatic intracerebral hemorrhage after tPA treatment was detected in patients with high cerebral microbleed burden (>10) when compared with patients with zero to 10 cerebral microbleeds (RR 12.10, 95% CI 4.36-33.57, P<0.001) or one to 10 cerebral microbleeds (RR 7.01, 95% CI 3.20-15.38, P<0.001) on pretreatment MRI.
In an individual-patient data meta-analysis, high cerebral microbleed burden was associated with increased likelihood of symptomatic brain bleeding before (unadjusted odds ratio 31.06, 95% CI 7.12-135.44, P<0.001) and after (adjusted OR 18.17, 95% CI 2.39-138.22, P=0.005) adjusting for potential confounders.
A study limitation was the lack of data on brain bleed risk by cerebral microbleed count stratification in four of the nine studies included in the meta-analysis and lack of information on key baseline characteristics in three of the nine studies. There was also incomplete information on antithrombotic medications taken before hospital admission for stroke treatment.
Despite these limitations, the researchers concluded that cerebral microbleed burden should be considered in the stroke, pre-tPA risk stratification setting.
"The challenge remains in identifying CMB burden without MRI in the setting of acute ischemic stroke management where only a noncontrast computed tomography is standard of care," they stated.
In an accompanying editorial, Mark Fisher, MD, of the University of California Irvine School of Medicine, noted that cerebral microbleeds have been shown to be present in more than 20% of older people, while they are rare in younger populations.
"Cerebral microbleeds have received enormous attention in the literature," he wrote. "Nevertheless, the nature of the underlying lesion of cerebral microbleeds has proved elusive."
Fisher noted that despite the meta-analysis findings, the critical factor relevant to tPA treatment "appears to be not the microbleeds themselves, but the arteriolar injury contributing to micro hemorrhage development."
"The principal challenge for the clinician addressing microbleeds in acute ischemic stroke will be to distinguish primary from secondary microbleeds," he wrote. "It is the disseminated processes of primary microbleeds that create the substrate of the brain vulnerable to arteriolar ischemic necrosis and development of intracerebral hemorrhage. The more restricted process or prior ischemic injury producing secondary microbleeds will be of far less concern in this context. Ultimately, the number of cerebral microbleeds present will be less important than the nature of the process driving microbleed development."

• Primary Source

  JAMA Neurology

  Source Reference: Tslvgoulis G, et al "Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden: a meta-analysis" JAMA Neurol 2016; DOI: 10.1001/jamaneurol.2016.0292.

• Secondary Source

  JAMA Neurology

  Source Reference: Fisher M "Cerebral microbleeds and thrombolysis: Clinical consequences and mechanistic implications" JAMA Neurol 2016; DOI: 10.1001/jamaneurol.2016.0576.