Vaso-Occlusive Crisis

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Wassim Y. Almawi - One of the best experts on this subject based on the ideXlab platform.

  • Protein Z polymorphisms associated with Vaso-Occlusive Crisis in young sickle cell disease patients
    Annals of hematology, 2012
    Co-Authors: Najat Mahdi, Khadija Al-ola, Tala M. Abu-hijleh, Farah M. Abu-hijleh, Mai S. Sater, Wassim Y. Almawi
    Abstract:

    We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) Vaso-Occlusive Crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P = 0.03), rs3024719 (P = 0.02), rs3024731 (P < 0.001), and rs3024735 (P < 0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P = 0.028) and rs3024735 (P = 0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P = 0.024), AGAA (P = 0.011), and GGTG (P = 0.002), and reduced frequency of AGTG haplotype (P = 0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (Pc = 0.001) and GGTG (Pc = 0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

  • Anti-annexin V IgG and IgM antibodies in sickle cell disease patients with Vaso-Occlusive Crisis
    Annals of Hematology, 2011
    Co-Authors: Mai S. Sater, Najat Mahdi, Iman K. Al-absi, Abeer M. Al-subaie, Fatema A. Mohammed, Wassim Y. Almawi
    Abstract:

    Vaso-Occlusive Crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients; however, its mechanisms are poorly understood. In view of their prothrombotic nature, we hypothesized that SCA-associated VOC may be due to the presence of anti-annexin V antibodies. Anti-annexin V antibodies were measured with ELISA in 177 VOC and 81 steady-state SCA patients. Anti-annexin V IgM and IgG concentrations were significantly higher in VOC patients than in steady-state patients and were associated with elevated VOC risk. After categorizing anti-annexin V antibodies, the adjusted odds ratio increased as the percentile value increased. Monovariate logistic regression analysis demonstrated a positive dose–effect relationship for anti-annexin V IgM with VOC, with increased VOC risk seen with increased antibody titers. Multivariate logistic regression analyses confirmed the association of anti-annexin V IgM, more so than IgG, as an independent VOC risk factor. Anti-annexin V IgG antibodies correlated positively with VOC type and negatively with HbF and age of VOC onset, while anti-annexin V IgM correlated positively with VOC type, duration, frequency, site, pain severity, hospitalization, and medication, and negatively with age of VOC onset and HbS levels. High levels of anti-annexin V IgM antibodies constitute a risk factor for VOC in SCA patients.

  • Predictive value of anti-annexin V autoantibodies in the follow-up of Vaso-Occlusive Crisis associated with sickle cell disease.
    Biomarkers in medicine, 2011
    Co-Authors: Mai S. Sater, Wassim Y. Almawi
    Abstract:

    Despite its monogenic nature, sickle cell disease (SCD) has a heterogenous phenotype [1] with a number of associated complications, which range in severity from mild to severe and crippling, and can affect virtually all organ systems [2]. Common SCD complications include hemolytic Crisis, splenic sequestration, aplastic Crisis, stroke, acute chest syndrome, osteomyelitis and Vaso-Occlusive Crisis (VOC). While some SCD patients remain asympomatic, others may present with one or more of these complications. Several studies have evaluated potential biomarkers for SCD VOC, which can be effectively used in identifying high-risk VOC patient groups, and in the patient follow-up, but with inconsistent findings. This article discusses the predictive value of anti-annexin V autoantibodies in monitoring the onset and severity of VOC, including the nature of the pain-alleviating medication.

  • Depression, anxiety, and stress comorbidities in sickle cell anemia patients with Vaso-Occlusive Crisis.
    Journal of pediatric hematology oncology, 2010
    Co-Authors: Najat Mahdi, Khadija Al-ola, Nahed Abdel Khalek, Wassim Y. Almawi
    Abstract:

    We investigated the association of sickle cell anemia (SCA) Vaso-Occlusive Crisis (VOC) with depression, anxiety, and stress disorders among Bahraini patients and controls. This was a cross-sectional study that involved administering Depression Anxiety Stress Scales (DASS-21) consisting of structured depression, anxiety, and stress scales to SCA patients with (n=138) and without (n=105) VOC. Multinomial regression and correlation analysis were used in assessing the association of VOC with depression and/or anxiety and/or stress, after adjusting for other covariates. Significantly higher proportion of VOC patients was found among the severe-extremely severe anxiety (P

  • Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with Vaso-Occlusive Crisis.
    European journal of haematology, 2009
    Co-Authors: Abeer Mohammed Al-subaie, Najat Mahdi, Khadija Al-ola, Iman K. Al-absi, Naglaa Fawaz, Ghada Ameen, Wassim Y. Almawi
    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.

Najat Mahdi - One of the best experts on this subject based on the ideXlab platform.

  • Protein Z polymorphisms associated with Vaso-Occlusive Crisis in young sickle cell disease patients
    Annals of hematology, 2012
    Co-Authors: Najat Mahdi, Khadija Al-ola, Tala M. Abu-hijleh, Farah M. Abu-hijleh, Mai S. Sater, Wassim Y. Almawi
    Abstract:

    We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) Vaso-Occlusive Crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P = 0.03), rs3024719 (P = 0.02), rs3024731 (P < 0.001), and rs3024735 (P < 0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P = 0.028) and rs3024735 (P = 0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P = 0.024), AGAA (P = 0.011), and GGTG (P = 0.002), and reduced frequency of AGTG haplotype (P = 0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (Pc = 0.001) and GGTG (Pc = 0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

  • Anti-annexin V IgG and IgM antibodies in sickle cell disease patients with Vaso-Occlusive Crisis
    Annals of Hematology, 2011
    Co-Authors: Mai S. Sater, Najat Mahdi, Iman K. Al-absi, Abeer M. Al-subaie, Fatema A. Mohammed, Wassim Y. Almawi
    Abstract:

    Vaso-Occlusive Crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients; however, its mechanisms are poorly understood. In view of their prothrombotic nature, we hypothesized that SCA-associated VOC may be due to the presence of anti-annexin V antibodies. Anti-annexin V antibodies were measured with ELISA in 177 VOC and 81 steady-state SCA patients. Anti-annexin V IgM and IgG concentrations were significantly higher in VOC patients than in steady-state patients and were associated with elevated VOC risk. After categorizing anti-annexin V antibodies, the adjusted odds ratio increased as the percentile value increased. Monovariate logistic regression analysis demonstrated a positive dose–effect relationship for anti-annexin V IgM with VOC, with increased VOC risk seen with increased antibody titers. Multivariate logistic regression analyses confirmed the association of anti-annexin V IgM, more so than IgG, as an independent VOC risk factor. Anti-annexin V IgG antibodies correlated positively with VOC type and negatively with HbF and age of VOC onset, while anti-annexin V IgM correlated positively with VOC type, duration, frequency, site, pain severity, hospitalization, and medication, and negatively with age of VOC onset and HbS levels. High levels of anti-annexin V IgM antibodies constitute a risk factor for VOC in SCA patients.

  • Depression, anxiety, and stress comorbidities in sickle cell anemia patients with Vaso-Occlusive Crisis.
    Journal of pediatric hematology oncology, 2010
    Co-Authors: Najat Mahdi, Khadija Al-ola, Nahed Abdel Khalek, Wassim Y. Almawi
    Abstract:

    We investigated the association of sickle cell anemia (SCA) Vaso-Occlusive Crisis (VOC) with depression, anxiety, and stress disorders among Bahraini patients and controls. This was a cross-sectional study that involved administering Depression Anxiety Stress Scales (DASS-21) consisting of structured depression, anxiety, and stress scales to SCA patients with (n=138) and without (n=105) VOC. Multinomial regression and correlation analysis were used in assessing the association of VOC with depression and/or anxiety and/or stress, after adjusting for other covariates. Significantly higher proportion of VOC patients was found among the severe-extremely severe anxiety (P

  • Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with Vaso-Occlusive Crisis.
    European journal of haematology, 2009
    Co-Authors: Abeer Mohammed Al-subaie, Najat Mahdi, Khadija Al-ola, Iman K. Al-absi, Naglaa Fawaz, Ghada Ameen, Wassim Y. Almawi
    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.

Siris Patel - One of the best experts on this subject based on the ideXlab platform.

  • Haptoglobin Genotypes Associated with Vaso-Occlusive Crisis in Sickle Cell Anemia Patients of Eastern India.
    Hemoglobin, 2021
    Co-Authors: Satyabrata Meher, Manoj Kumar Mohapatra, Siris Patel, Snehadhini Dehury, Pradeep Kumar Mohanty, Kishalaya Das, Sarmila Sahoo, Bimal Prasad Jit, Padmalaya Das, Bisnu Prasad Dash
    Abstract:

    Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting Vaso-Occlusive Crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (p 

  • Association of plasma homocysteine level with Vaso-Occlusive Crisis in sickle cell anemia patients of Odisha, India
    Annals of Hematology, 2019
    Co-Authors: Satyabrata Meher, Siris Patel, Snehadhini Dehury, Mahendra M. Maske, Bisnu Prasad Dash, Pradeep Kumar Mohanty
    Abstract:

    Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation‚ and hemato-biochemical parameters in SCA and their effect on the Vaso-Occlusive Crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher ( p  

  • Procalcitonin as a biomarker of bacterial infection in sickle cell Vaso-Occlusive Crisis.
    Mediterranean journal of hematology and infectious diseases, 2014
    Co-Authors: Dilip Kumar Patel, Manoj Kumar Mohapatra, Ancil George Thomas, Siris Patel, Prasanta Purohit
    Abstract:

    Bacterial infection is an important trigger of Vaso-Occlusive Crisis (VOC) in sickle cell anaemia (SCA). SCA Patients with VOC have signs of inflammation and it is difficult to diagnose bacterial infection in them. This study was undertaken to evaluate serum procalcitonin (PCT) as a biomarker of bacterial infection in acute sickle cell Vaso-Occlusive Crisis. Hundred SCA patients were studied at Sickle Cell Clinic and Molecular Biology Laboratory, V.S.S. Medical College, Burla, Odisha, India. SCA was diagnosed by haemoglobin electrophoresis, HPLC and molecular analysis. Patients were divided into 3categories namely Category-A (VOC/ACS with fever but without evidence of bacterial infection-66 patients); Category-B (VOC with fever and documentedbacterial infection-24 patients); and Category-C (Patients in steady statewithout VOC/ACS or fever-10 patients). Investigations like complete blood count, C-reactive protein estimation and PCT measurement was done in all the cases. There was no significant difference in total leucocytes count and C-reactiveprotein values between category A and B. In category A the PCT level was 0.5ng/mL with 87.5% of cases having >2ng/mL. In category C, PCT value was 2ng/mL is indicative of bacterial infection necessitating antimicrobial therapy. Patients with indeterminate PCT value of0.5-2ng/mL, need a repeat PCT estimation or an empirical antibiotic therapyawaiting the availability of microbiological report as deemed necessary.

Pradeep Kumar Mohanty - One of the best experts on this subject based on the ideXlab platform.

  • Haptoglobin Genotypes Associated with Vaso-Occlusive Crisis in Sickle Cell Anemia Patients of Eastern India.
    Hemoglobin, 2021
    Co-Authors: Satyabrata Meher, Manoj Kumar Mohapatra, Siris Patel, Snehadhini Dehury, Pradeep Kumar Mohanty, Kishalaya Das, Sarmila Sahoo, Bimal Prasad Jit, Padmalaya Das, Bisnu Prasad Dash
    Abstract:

    Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting Vaso-Occlusive Crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (p 

  • Association of plasma homocysteine level with Vaso-Occlusive Crisis in sickle cell anemia patients of Odisha, India
    Annals of Hematology, 2019
    Co-Authors: Satyabrata Meher, Siris Patel, Snehadhini Dehury, Mahendra M. Maske, Bisnu Prasad Dash, Pradeep Kumar Mohanty
    Abstract:

    Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation‚ and hemato-biochemical parameters in SCA and their effect on the Vaso-Occlusive Crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher ( p  

Khadija Al-ola - One of the best experts on this subject based on the ideXlab platform.

  • Protein Z polymorphisms associated with Vaso-Occlusive Crisis in young sickle cell disease patients
    Annals of hematology, 2012
    Co-Authors: Najat Mahdi, Khadija Al-ola, Tala M. Abu-hijleh, Farah M. Abu-hijleh, Mai S. Sater, Wassim Y. Almawi
    Abstract:

    We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) Vaso-Occlusive Crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P = 0.03), rs3024719 (P = 0.02), rs3024731 (P < 0.001), and rs3024735 (P < 0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P = 0.028) and rs3024735 (P = 0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P = 0.024), AGAA (P = 0.011), and GGTG (P = 0.002), and reduced frequency of AGTG haplotype (P = 0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (Pc = 0.001) and GGTG (Pc = 0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

  • Depression, anxiety, and stress comorbidities in sickle cell anemia patients with Vaso-Occlusive Crisis.
    Journal of pediatric hematology oncology, 2010
    Co-Authors: Najat Mahdi, Khadija Al-ola, Nahed Abdel Khalek, Wassim Y. Almawi
    Abstract:

    We investigated the association of sickle cell anemia (SCA) Vaso-Occlusive Crisis (VOC) with depression, anxiety, and stress disorders among Bahraini patients and controls. This was a cross-sectional study that involved administering Depression Anxiety Stress Scales (DASS-21) consisting of structured depression, anxiety, and stress scales to SCA patients with (n=138) and without (n=105) VOC. Multinomial regression and correlation analysis were used in assessing the association of VOC with depression and/or anxiety and/or stress, after adjusting for other covariates. Significantly higher proportion of VOC patients was found among the severe-extremely severe anxiety (P

  • Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with Vaso-Occlusive Crisis.
    European journal of haematology, 2009
    Co-Authors: Abeer Mohammed Al-subaie, Najat Mahdi, Khadija Al-ola, Iman K. Al-absi, Naglaa Fawaz, Ghada Ameen, Wassim Y. Almawi
    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.