There was no benefit of treatment within 3 hours of onset.168 See Tables XXXV and XXXVI in online Data Supplement 1. 3.5.2. Time Windows (Continued) COR LOE New, Revised, or Unchanged 3.5.4. Other Specific Circumstances COR LOE New, Revised, or Unchanged IV alteplase for adults presenting with an AIS with known sickle cell disease can be beneficial. IIa B-NR New recommendation. A case-control analysis using the population from the AHA GWTG-Stroke registry, including 832 cases with sickle cell disease (all adults) and 3328 age-, sex-, and race-matched controls without sickle cell disease with similar severity of neurological deficits at presentation, showed that sickle cell disease did not have a significant impact on the safety or the outcome at discharge of treatment with IV alteplase.169 See Table XXXVII in online Data Supplement 1. 2. In patients with a hyperdense MCA sign, IV alteplase can be beneficial. IIa B-NR New recommendation. Analyses of data from RCTs of IV alteplase for AIS have shown no statistically significant deleterious interaction on clinical outcomes between alteplase treatment and the hyperdense MCA sign on baseline CT. In the NINDS rt-PA trial, there was no interaction between hyperdense MCA sign and treatment for outcomes at 3 months measured by any of the 4 clinical scales (mRS score 0 1, NIHSS score 0 1, Barthel Index score 95, Glasgow Outcome Scale score 0 1) or for death.170 In IST-3, no significant interaction of the hyperdense MCA sign with benefit of alteplase measured by the Oxford Handicap Score at 6 months was observed.171,172 See Table XXXVIII in online Data Supplement 1. 3.5.5. 