Alternative Viewpoint of “Alteplase Therapy for Acute Ischemic Stroke in Pregnancy: Two Case Reports and a Systematic Review of the Literature”

We read with great enthusiasm the article by Ryman et al and wish to highlight a few key concepts not mentioned in their article. Although a large proportion of data for alteplase in acute ischemic stroke (AIS) remains controversial, we propose that the hemostatic variances seen during pregnancy make the women in this patient population ideal candidates for thrombolysis. Pregnancy is associated with a hypercoagulable state secondary to increased clotting factor production, decreased protein C and S activity, and decreased natural thrombolytic activity. It would be expected that clots formed during pregnancy would be fibrin rich, presenting an ideal therapeutic target for alteplase. This is in contrast to the typically more calcified composition of cardioembolic strokes, offering a theoretical explanation for the varied responses to alteplase seen in patients with this type of stroke. Also, although actual body weight has been the only dosing strategy evaluated for AIS during pregnancy in the literature thus far, lower dosing strategies were evaluated in select cohorts that have largely shown success. 5 Given the variances during pregnancy in volume of distribution, cardiac output, plasminogen activator inhibitor concentration, and hepatic clearance, it is reasonable to expect altered serum alteplase concentrations that may affect drug concentration and delivery to affected vessels. Therefore, optimal dosing strategies throughout each trimester should continue to be an area of active research. Given that the fatal bleed risk extends beyond just intracranial hemorrhages for pregnant patients, a question remains as to whether those at high risk for uterine hemorrhage or with mild stroke severity should bypass alteplase administration in favor of thrombectomy or antiplatelet therapies. Lastly, with increasing use of tenecteplase for ischemic stroke, it will be important to consider if alteplase alone or fibrinolytics as a class are safe and effective in pregnancy.