Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes

Abstract

Objective: To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months.

Methods: Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke-II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0-1 or equal to prestroke mRS) and good (mRS score 0-2 or equal to prestroke mRS) outcomes at 3 months.

Results: We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [adjOR] for an increase of 1,000 neutrophils = 1.21 and adjOR 1.11, respectively), death (adjOR 1.16 and adjOR 1.08), and excellent (adjOR 0.87 and adjOR 0.85) and good (adjOR 0.86 and adjOR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR ≥4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adjOR: 1.97-6.98) compared to patients with NLR <4.80.

Conclusions: Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.

Figure 1. Correlation between the onset-to-sample time and neutrophils, leukocytes, and neutrophil to lymphocyte ratio (NLR)

Figure 2. Comparison of outcomes between patients divided per quartiles for neutrophil count, leukocyte count, and neutrophil to lymphocyte ratio (NLR)

Comparison of outcomes between patients from the lowest (Q1) to the highest (Q4) quartiles for neutrophil count, leukocyte count, and NLR. See text for definitions. sICH = symptomatic intracerebral hemorrhage.

Figure 3. Predictive values of neutrophil count, leukocyte count, and neutrophil to lymphocyte ratio (NLR) for the 4 endpoints

Receiver operating characteristic curves for the 4 endpoints. (A) Area under the curve for symptomatic intracerebral hemorrhage (sICH) 0.68, confidence interval (CI) 0.60–0.76 for neutrophils; 0.51, CI 0.44–0.58 for leukocytes; and 0.73, CI 0.66–0.80 for NLR. (B) Area under the curve for death 0.66, CI 0.59–0.72 for neutrophils; 0.56, CI 0.49–0.62 for leukocytes; and 0.68, CI 0.62–0.75 for NLR. (C) Area under the curve for excellent outcomes 0.63, CI 0.59–0.66 for neutrophils; 0.52, CI 0.48–0.56 for leukocytes; and 0.66, CI 0.62–0.70 for NLR. (D) Area under the curve for good outcomes 0.64, CI 0.60–0.68 for neutrophils; 0.53, CI 0.49–0.57 for leukocytes; and 0.67, CI 0.63–0.71 for NLR.