Haptoglobin-Vasospasm Project

BACKGROUND: Vasospasm is a prolonged constriction of a cerebral artery that occurs after subarachnoid hemorrhage (SAH). The reduction of blood flow to the brain during vasospasm often causes neurological injury in addition to that already inflicted on the patient by the SAH. Vasospasm is caused by hemoglobin as it is released from decaying red blood cells in the subarachnoid blood clot. Such extracellular hemoglobin is normally bound and neutralized by the protein haptoglobin, which is found outside of red blood cells in the blood serum. Haptoglobin is composed of two alpha-beta subunit dimers, and there are two alleles that encode different alpha subunits (alpha1, alpha2). Each person has two constitutively-expressed alleles for the alpha subunit, therefore a person's haptoglobin protein will be one of three major types: alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2. In biochemical assays the ability to bind and neutralize hemoglobin is reduced in haptoglobin types that include the alpha2 subunit, which may affect their in vivo ability to bind and neutralize hemoglobin released from the subarachnoid clot after SAH.

HYPOTHESIS: We hypothesize that the incidence of vasospasm will be lower in SAH patients who express haptoglobin alpha1-alpha1, compared with SAH patients who express haptoglobin alpha1-alpha2 or haptoglobin alpha2-alpha2.

METHODS: We propose a prospective study that will correlate the development of vasospasm with the haptoglobin types expressed by the SAH patients. The primary measure of vasospasm will be the development of new neurological injury as measured by a modified Glasgow coma scale and the NIH stroke scale. Baseline neurological condition will be assessed with both scales on post-hemorrhage day 2, and new neurological injury will be diagnosed as a deterioration from the baseline that is not attributable to other causes. The secondary measure of vasospasm will be the development of arterial constriction. Eleven major intracranial arteries will be assessed daily with transcranial Doppler ultrasonography for increased flow rates, which will be confirmed as vasospasm by cerebral angiography. The haptoglobin type of the SAH patients will be determined from blood samples by means of starch gel electrophoresis.