Pregnancy and Ischemic Stroke: Is Thrombolysis an Option?

Abstract & Commentary

By Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College, Cornell University. Dr. Jamieson is a consultant for Boehringer Ingelheim and Merck, and is on the speaker's bureau for Boehringer Ingelheim, Merck, Ortho-McNeil, and Pfizer.
This article originally appeared in the August issue of
Neurology Alert. It was edited by Matthew E. Fink, MD, and peer reviewed by M. Flint Beal, MD. Dr. Fink is Vice Chairman, Professor of Clinical Neurology, Weill Cornell Medical College, Chief of Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital, and Dr. Beal is Professor and Chairman, Department of Neurology, Cornell University Medical College. Drs. Fink and Beal report no financial relationships relevant to this field of study.

Synopsis: rtPA thrombolysis may be used safely in pregnant women.

Source: Murugappan A, et al. Thrombolytic Therapy of Acute Stroke During Pregnancy. Neurology. 2006;66:768-770.

Pregnancy is a prothrombotic state which is rarely associated with ischemic arterial stroke. However, when a stroke occurs, especially in later pregnancy, the options for therapy may be limited. The additional consideration of fetal outcome complicates therapy of the mother, and pregnancy has generally been considered a contraindication for thrombolysis. The confidence and experience in the use of thrombolysis in acute ischemic stroke has increased in the past decade. Although the 3-hour window has remained the standard for intravenous (IV) delivery of recombinant tissue plasminogen activator (rtPA), intra-arterial (IA) delivery has expanded the treatment time and population. The drug is pregnancy category C (unknown safety), with concerns about fetal and maternal hemorrhage risk and teratogenicity. However, animal data have not indicated associated fetal anomalies, and the large molecule does not cross the placenta. Several papers published in 2006 have illustrated that women at different stages of pregnancy can be treated with thrombolysis, either IV or IA, without excess risk to the patient, and with the potential of a viable pregnancy.

Earlier in the year in Neurology,1 a series of 8 patients who underwent IV or IA thrombolytic treatment of ischemic stroke was reported. Half of the patients were treated with urokinase, as opposed to rtPA, and 2 patients had venous, rather than arterial, thrombosis. There was one fatal complication from angioplasty (with death of the fetus), and 3 pregnancies were medically terminated. Two healthy babies were delivered. There was one spontaneous first trimester abortion, as well as a fetal demise due to lethal chromosome abnormalities. Murugappan and colleagues reviewed the medical literature and noted that in the mainly non-stroke related cases of thrombolysis during pregnancy, the premature delivery rate was not increased. There was no indication of teratogenicity.

Case reports note success with the treatment. A woman, 13 weeks pregnant, on subcutaneous heparin because of a mechanical mitral valve, was given standard protocol IV rtPA for a left middle cerebral artery infarct.2 She was restarted on warfarin for the rest of her uncomplicated pregnancy, and she delivered a healthy baby at 37 weeks.

In a review article of 28 published cases of treatment with rtPA in pregnancy,3 10 women with stroke were identified. Six of the cases were from an abstract of the recently published paper noted above.1 One woman with cerebral sinus thrombosis was treated successfully with thrombolysis, and had an uneventful delivery. In the remaining 3 cases (2 IV, one IA), there was good neurological recovery in 2 of the women, and 3 healthy babies were delivered. In the remaining cases where rtPA was given for thrombosed prosthetic cardiac valves, pulmonary embolism, deep vein thrombosis, or fetal complications were rare and felt to be related to the underlying maternal condition, not the thrombolytic therapy. An addendum to the review article reported a woman with a left middle cerebral artery stroke at 23 weeks, treated with IV rtPA, with variable neurological recovery. She delivered successfully at 33 weeks.

Arterial and venous infarcts can be neurologically devastating during pregnancy, with concern about the outcome of both the patient and fetus. While experience with the use of rtPA during pregnancy is still limited, these reported successes encourage the consideration of rtPA in pregnant women with ischemic stroke. As experience with thrombolysis in acute stroke increases, pregnancy does not appear to be an absolute contraindication, especially in the absence of other effective alternatives. Without specific guidelines for its use in pregnancy, the guidelines for rtPA use in general should apply to the woman who suffers an acute ischemic stroke during pregnancy.

References

1. Murugappan A, et al. Thrombolytic Therapy of Acute Stroke During Pregnancy. Neurology. 2006;66:768-770.

2. Weise KM, et al. Intravenous Recombinant Tissue Plasminogen Activator in a Pregnant Woman with Cardioembolic Stroke. Stroke. 2006; Epub Ahead of Print. www.strokeaha.org

3. Leonhardt G, et al. Thrombolytic Therapy in Pregnancy. J Thromb Thrombolysis. 2006;21:271-276.