Volume 83, Issue 6 pp. 579-585

Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with vaso-occlusive crisis

Abeer M. Al-Subaie

Abeer M. Al-Subaie

Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

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Naglaa A. Fawaz

Naglaa A. Fawaz

Haematology Department, Sultan Qaboos University Hospital, Muscat, Oman

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Najat Mahdi

Najat Mahdi

Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

Department of Pediatrics, Salmaniya Medical Complex, Manama, Bahrain

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Iman K. Al-Absi

Iman K. Al-Absi

Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

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Khadija Al-Ola

Khadija Al-Ola

Department of Pediatrics, Salmaniya Medical Complex, Manama, Bahrain

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Ghada Ameen

Ghada Ameen

Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

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Wassim Y. Almawi

Wassim Y. Almawi

Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain

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First published: 10 November 2009
Citations: 7
Wassim Y. Almawi, PhD, Department of Medical Biochemistry, College of Medicine & Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain. Tel: +973-39 71 71 18; Fax: +973-17 271 090; e-mail: [email protected]

Abstract

Objectives: Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients.

Patients/methods: This was a case–control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP.

Results: Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49–5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40–7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs).

Conclusion: This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC.

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