Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage

Background: Vasospasm is a prolonged constriction of a cerebral artery that is induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood clot also contains the protein haptoglobin, which acts to neutralize hemoglobin. Because the haptoglobin alpha gene is dimorphic, a person can expresses only one of three types of haptoglobin (alpha 1 - alpha 1, alpha 1 - alpha 2, or alpha 2 - alpha 2) depending on the alpha subunit genes he or she inherits. Each of these three haptoglobin types has different antihemoglobin activities; therefore, haptoglobin may influence the development of vasospasm differently in various patients with SAH. Objective: To determine whether SAH patients who have haptoglobin containing the alpha 2 subunit would be more likely to develop vasospasm than would be SAH patients who have haptoglobin alpha 1 - alpha 1. Methods and Results: A total of 32 patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type was determined by polyacrylamide gel electrophoresis. The primary measure for vasospasm was increased blood flow velocities as detected by daily transcranial Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with haptoglobin alpha 1 - alpha 1 (22%) had development of "possible" vasospasm as measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha 2 subunit (either the alpha 1 - alpha 2 or alpha 2 - alpha 2 haptoglobin types) had development of "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral angiography performed between 3 and 14 days after SAH. Similar results (17% vs 56%) were seen between these groups in those patients who underwent cerebral angiography, although its inconsistent use limited the strength of the statistical comparison. Conclusions: Haptoglobins containing the alpha 2 subunit seem to be associated with a higher rate of vasospasm than is haptoglobin alpha 1 - alpha 1.