Published Online
on August 26, 2004

A more recent version of this article appeared on October 1, 2004

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Submitted on April 28, 2004
Revised on June 16, 2004
Accepted on July 7, 2004

The Platelet GP IIIa Polymorphism HPA-1 (PlA) Protects Against Subarachnoid Hemorrhage

Juan A. Iniesta PhD; Rocio González-Conejero PhD; Claudio Piqueras MD; Vicente Vicente PhD; and Javier Corral PhD^*

From the Hematology and Oncology Service (R.G.-C., V.V., J.C.), Centro Regional de Hemodonación, Universidad de Murcia, Spain; the Neurology Section (J.A.I.), Hospital General Universitario, Murcia, Spain; and the Neurosurgery Service (C.P.), Hospital Virgen de la Arrixaca, Murcia, Spain.

^* To whom correspondence should be addressed. E-mail: jcc{at}um.es.

Background and Purpose--Few genetic modifications have been identified to be associated with subarachnoid hemorrhage (SAH), most of them playing a role in the formation or size of aneurysms.

Methods--We evaluated the role of common and functional polymorphisms affecting the main platelet adhesive glycoproteins (GP) (GPIIIa: HPA-1; GPIa: HPA-5 and C807T; GPIb: HPA-2 and VNTR) in the risk for development of the disease and in the severity of the onset. The study was performed in 103 patients with SAH, 103 matched controls, and 473 subjects from the general population.

Results--The HPA-1b (PlA2) allele significantly protected against SAH (OR, 0.48; 95% CI, 0.24 to 0.96; P=0.037). Interestingly, patients carrying this allele displayed larger aneurysms, but the extension of their hemorrhage and the clinical grade at presentation was significantly lower when compared with patients HPA-1 a/a (11.9±2.8 mm versus 8.8±2.2 mm, P=0.0001. Fisher grade 2: 68.4% versus 20%; P=0.0001; Hunt and Hess score <IV; 84.2% versus 53.8%; P=0.0187, respectively). The protection of the HPA-1b allele seemed to be exacerbated by the simultaneous presence of the HPA-2b allele. Thus, no patient carried this combination, which was present in 7.8% of controls (P=0.007).

Conclusions--We present the first evidence suggesting a protective role for the platelet GPIIIa HPA-1b allele in SAH. The suggested platelet hyper-reactivity determined by this allele could reduce the risk to suffer SAH, specially if the aneurysm is small, attenuate the severity of the hemorrhage, and reduce the clinical grade at presentation. This effect might be amplified by the simultaneous combination with the GPIb HPA-2b allele.

Key words: aneurysm • genetics • hemostasis • subarachnoid hemorrhage

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