Smaller Lumens Explain Women's TPA Response


KISSIMMEE, FLA. — Differences in vessel size may explain why women have higher recanalization rates than men as well as better final outcomes following intravenous thrombolysis for acute ischemic stroke, Dr. David S. Liebeskind reported at the 31st International Stroke Conference.

These differences have been demonstrated in previous studies and a number of possible pathophysiologic explanations have been offered. Intravenous thrombolysis was evaluated in 100 men and 100 women based on factors such as anatomy and flow physiology to evaluate the possibility that vessel size contributes to the differences, or more specifically, that “angio-architectural differences predispose women to recanalize more efficiently due to favorable clot geometry,” said Dr. Liebeskind.

The cross-sectional lumen areas of the proximal middle cerebral, supraclinoid internal carotid, and distal basilar arteries were measured in the participants using 3-D CT angiograms. Weight and height data were used to calculate tissue plasminogen activator (TPA) dose, and patient data were used to model clot volume and ratio of exposed surface area to total clot volume.

Intracranial arteries are significantly smaller in women than in men, said Dr. Liebeskind of the University of California, Los Angeles. The proximal middle cerebral artery (MCA) in women vs. men averaged 0.049 vs. 0.052 cm

Similar statistically significant differences were noted in terms of clot volume (proximal MCA: 0.078 vs. 0.089 cm

Women were more likely to have actual body weight above ideal body weight and greater differences between actual and ideal body weight, compared with men. This means an increased TPA-to-surface area ratio, creating discordance between TPA dosage (based on weight) and vessel size, resulting in relatively higher TPA dosing in women, compared with men.

The “theoretical thrombolysis” used in this study suggests that the smaller vessel size and lesser clot volume seen in women, along with relatively higher doses of TPA, contribute to their improved responsiveness to intravenous thrombolysis, Dr. Liebeskind said at the conference, which was sponsored by the American Stroke Association. Increases in radius or length of the patent channel that may form within the clot further accentuate the differences seen in surface area-to-clot volume ratio, he added.

Although the study is limited by its theoretical nature and simplified anatomical characterizations without regard to potentially critical pathophysiology, the findings suggest that adjusting the dosing of intravenous TPA to body frame size could optimize recanalization in both men and women, he concluded.

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