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

Abstract

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) Pϭ0.0187, 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 (Pϭ0.007). 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.

Allelic frequencies of HPA‐1 to 5 human platelet antigens in patients infected with hepatitis C virus

“…The study of HPAs polymorphisms should not be restricted to thrombotic disorders [Iniesta et al, 2004], because the integrins are not expressed exclusively in platelets, but have been identified in other cells such as tumor cells or epithelial cells. Polymorphisms affecting these molecules could play a role in other situations or diseases, as suggested in allogeneic-hematopoietic stem cell transplantation [García-Malo et al, 2004] or cancer [Ayala et al, 2003].…”

Association of Human Platelet Alloantigen 1 through 5 Polymorphisms with Ischemic Stroke

“…Other studies failed to demonstrate an association of HPA-1 a/b [27,28,29,30,31], and other HPA polymorphic variants [27, 28] with stroke. These apparently contradicting results obtained from earlier studies may be due to differences in the selection of the study subjects [29, 30], sample size [28, 29], and ethnic origin of the study subjects [8, 30, 31]. …”

The systemic implications of aneurysmal subarachnoid hemorrhage

“…Iniesta et al found a link between functional polymorphisms affecting the main platelet adhesive glycoproteins and a reduced risk of aneurysmal SAH, decreased extension of hemorrhage, and higher clinical grade at presentation [176]. In a large SAH cohort, moderate thrombocytopenia (81,000-120,000/mm 3 ) was noted in 20.7% of patients and severe thrombocytopenia (51,000-80,000/mm 3 ) in 6.2% [6].…”