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Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043). Conclusions: The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels

Estrogens have proven vasoprotective properties against atherosclerosis that depend on the direct effect on vascular smooth muscle and endothelium and on systemic actions that imply serum lipids, coagulation and fibrinolytic cascades, vasoactive proteins and antioxidant systems. They also have neuroprotective effects against cerebral ischemia that include antioxidant and anti-inflammatory effects, modulation of protein synthesis, inhibition of apoptosis and trophic effects and preservation of microvascular blood flow in the ischemic area. Estrogenic actions depend on activation of specific estrogen receptors that modulate gene expression and produce long-term effects on vascular endothelial and smooth muscle cells, neurons and glia, on interaction with plasma membrane sites that produce rapid non-genomic actions and also on receptor-independent mechanisms. This paper reviews what it is known about the mechanisms underlying the vaso- and neuroprotective effects of estrogens. Experimental and clinical evidences of such protective effects are also discussed. Therapeutical implications for stroke prevention and treatment derived from the available evidence are considered.

Undeniable advances have been made in clinical and experimental investigation into the pathophysiology, diagnosis, and treatment of cerebral ischemia. However, with the exception of intravenous thrombolysis and some neuroprotectors, such as citicoline, the majority of the drugs successfully tested in experimental studies have failed in clinical trials. Valuable lessons for the improvement of research methodology and appropriate coordination of experimental and clinical research can be learnt from the analysis of discrepancies between the laboratory and clinic, which will allow us to increase the power and cost-effectiveness of the studies. In addition, this progress has opened the way for the investigation of very promising new therapeutic strategies, such as combined pharmacological and mechanical thrombolysis, thrombolysis and neuroprotection, or the combination of various neuroprotectors, antiapoptotic therapies, and neurorestoration therapies, such as stem cell transplants.