Platelet derived growth factor-CC isoform is associated with hemorrhagic transformation in ischemic stroke patients treated with tissue plasminogen activator

ObjectivePlatelet derived growth factor-CC (PDGF-CC) isoform is activated by tissue plasminogen activator (tPA) regulating blood brain barrier permeability after ischemia. We aimed to study the association of PDGF isoforms serum levels with hemorrhagic transformation (HT) and edema after thrombolytic treatment in ischemic stroke.MethodsWe studied 129 patients with ischemic stroke treated with tPA within the first 4.5 h (h) from stroke onset. CT was performed on admission and at 24-36 h. On the 2nd CT, HT was classified according to ECASS II criteria, and severe brain edema was diagnosed if extensive swelling causing any shifting of the structures of the midline was detected. PDGF-AA, PDGF-AB, PDGF-BB and PDGF-CC serum levels were analyzed by ELISA on admission (before tPA bolus), at 24 and 72 h.ResultsPatients who developed HT showed only higher levels of PDGF-CC isoform on admission and at 24 h (all p < 0.0001). In the multivariate analysis, PDGF-CC levels on admission (OR, 1.02; CI 95%, 1.00-1.04) and at 24 h (OR, 1.05; CI 95%, 1.02-1.08) were independently associated with HT after adjustment by confounding factors. On the other hand, patients with severe edema showed also higher levels of PDGF-CC on admission and at 24 h (p < 0.0001), but this statistical association was lost in the logistic regression analysis. PDGF-CC levels ≥ 175 ng/mL at 24 h predict the development of PH with a sensitivity of 90% and specificity of 88% (area under the curve 0.936; p < 0.0001).ConclusionIncreased PDGF-CC levels after tPA treatment is associated with HT.

► We study the role of PDGF isoforms on hemorrhagic transformation and edema in stroke. ► PDGF-CC serum levels are associated to hemorrhagic transformation and severe edema. ► Increased PDGF-CC levels after tPA treatment are associated with HT.