Stroke Rounds: Neutrophil Count Predicts tPA Brain Bleeds

More research needed to possibly prevent excess bleeding from tPA admistration. If we had anything other than craptastic stroke associations we could give this problem to them to research and solve for protocols. But we don't so survivors are once again getting screwed over. Deal with it, nobody is on the survivors side.
http://www.medpagetoday.com/Cardiology/Strokes/53566?
Elevated baseline neutrophil count was predictive of a higher risk for brain bleeds and poor outcomes at 3 months in stroke patients receiving recombinant tissue plasminogen activator (tPA), researchers reported.
Both neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with symptomatic intracerebral hemorrhage (sICH) and death in patients treated with tPA.

Advertisement

Patients with an NLR of 4.80 or greater had an adjusted odds ratio of 3.7 for sICH (95% CI 1.97-6.68), compared to patients with lower NLRs, researcher Regis Bordet, MD, PhD, of the University of Lille in France, and colleagues wrote in the journal Neurology.
The findings suggest that neutrophil to lymphocyte ratio could represent a simple and inexpensive biomarker for identifying patients at high risk for brain bleeds, but the researchers noted that more study is needed to determine its value in clinical practice.
"Our results need to be replicated in an independent cohort of patients," they wrote. "Even if they are confirmed, we cannot recommend the use of NLR in routine practice for the selection of patients to be treated with recombinant tPA, because it will increase delays in all patients, for a not yet proven benefit in a few of them."
Findings from several recent studies suggest that NLR predicts both short- and long-term outcomes among stroke patients, but these studies had limitations, including the lack of information on thrombolytic therapy and small size, the researchers wrote.
Their newly published study included 846 stroke patients treated with tPA (median age 71 years, 50.8% men), with blood samples for leukocyte, neutrophil, and lymphocyte counts drawn before treatment.
The primary endpoint was sICH and secondary endpoints included death and outcomes at 3 months, as measured by modified Rankin Scale.
Findings included:

• Neutrophil count and NLR independently predicted sICH, death, and outcomes at 3 months
• Total leukocyte count was not associated with any of these outcomes
• The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32), with these patients having a 3.71-fold increased risk for sICH, compared to patients with lower NLR
• In patients with a NLR of ≥4.80, the incidence of sICH was 13.6% (34/250), while in patients with NLR <4.80 it was 3.1% (17/553) (P<0.001)

"Our study suggests that higher neutrophil counts are associated with worse outcomes, regardless of the reason for neutrophil increase," the researchers wrote. "Although our study was not designed to understand the underlying mechanism, if a causal relationship exists, this effect could be mediated by the release of matrix metalloproteinase-9 (MMP-9), as suggested in animal and human studies."
They added that studies of biomarkers such as MMP-9, chemotaxis, inflammation, and tissue necrosis collected before thrombolysis are needed, as well as studies examining the underlying molecular mechanism driving the association.
"Although it has not been proven in human studies that a reduction in the level of neutrophils improves outcomes, animal studies have shown that a pharmacologic neutropenia induced by vinblastine and by RP3-anti-rat neutrophils monoclonal antibodies is associated in rats with prevention of endothelial dysfunction after experimental cerebral ischemia," they wrote.
In an editorial published with the study, Leonardo Roever, MHS, of Federal University of Uberlandia, Brazil and Steven R. Levine, MD, of SUNY Downstate Medical Center in Brooklyn, N.Y., wrote that the findings suggest that higher neutrophil counts are associated with worse stroke outcomes, "regardless of the mechanism by which neutrophils increase."
"(The researchers) have identified an easily available biomarker that may enhance prediction of risk of sICH after IV rtPA for stroke," they wrote. "These results need validation in separate cohorts of patients before we shift out of neutral gear and move forward to use this biomarker clinically."
Study strengths identified by the investigators include the prospective collection of data in two countries, the homogeneous groups of patients treated with tPA in routine practice, and the drawing of blood samples prior to tPA administration. Patients included in the study were representative of patients treated with tPA for ischemic stroke according to demographic characteristics, medical history, and vascular risk.
The lack of information on pre-existing infections and fever occurring during the first post-stroke days was cited by the researchers as a significant study limitation. Fever and infection are associated with worse outcomes in stroke patients. Another limitation was the possibility that neutrophil counts could have been been influenced by stroke severity.
Primary Source
    Neurology
    Source Reference: Maestrini I, et al "Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes" Neurology 2015; DOI: 10.1212/WNL.0000000000002029.

• Primary Source

  Neurology

  Source Reference: Maestrini I, et al "Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes" Neurology 2015; DOI: 10.1212/WNL.0000000000002029.