Association of silent infarcts in sickle cell anemia with decreased annexin A5 resistance

Research output: Contribution to journalArticle

Abstract

Background: Sickle cell anemia (SCA) is characterized by abnormally shaped, adhesive RBCs that interact with white blood cells and the endothelium, leading to chronic hemolysis, vasculopathy and a prothrombotic state. About 10% of subjects with a thrombotic event in the general population will have an associated antiphospholipid (aPL) antibody. One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of the potent anticoagulant annexin A5 or Annexin A5 resistance (A5R). We designed a pilot study assessing the presence of aPL antibodies and disruption of A5R in pediatric sickle cell subjects. Methods: 39 subjects with SCA participated in this study. A5R, DRVVT, anti-β2GP1, anti-β2GP1, anti-phosphatidylserine and anti-cardiolipin antibody assays were performed. Results: There was a high prevalence of abnormal A5R despite a low prevalence of antiphospholipid antibodies. Multivariate logistic regression analyses showed an association with silent infarcts (p = 0.015), lower hemoglobin (p = 0.037), older age (p = 0.047) and abnormal A5R. Conclusion: We report an association between annexin A5 resistance and presence of silent infarct, low hemoglobin, and older age in a subgroup of SCA subjects. A potential role for perturbed A5R in the pathophysiology of SCA needs to be evaluated further.

Original languageEnglish (US)
JournalBlood Cells, Molecules, and Diseases
DOIs
StateAccepted/In press - 2017

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Antiphospholipid Antibodies
Annexin A5
Sickle Cell Anemia
Hemoglobins
Cardiolipins
Phosphatidylserines
Hemolysis
Adhesives
Anticoagulants
Endothelium
Anti-Idiotypic Antibodies
Leukocytes
Logistic Models
Regression Analysis
Pediatrics
Population

Keywords

  • Annexin A5 resistance
  • Antiphospholipid antibody
  • Sickle cell disease
  • Silent infarcts

ASJC Scopus subject areas

  • Molecular Medicine
  • Hematology
  • Molecular Biology
  • Cell Biology

Cite this

@article{592e6b4ae8194affbb37d6b08db003ec,
title = "Association of silent infarcts in sickle cell anemia with decreased annexin A5 resistance",
abstract = "Background: Sickle cell anemia (SCA) is characterized by abnormally shaped, adhesive RBCs that interact with white blood cells and the endothelium, leading to chronic hemolysis, vasculopathy and a prothrombotic state. About 10{\%} of subjects with a thrombotic event in the general population will have an associated antiphospholipid (aPL) antibody. One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of the potent anticoagulant annexin A5 or Annexin A5 resistance (A5R). We designed a pilot study assessing the presence of aPL antibodies and disruption of A5R in pediatric sickle cell subjects. Methods: 39 subjects with SCA participated in this study. A5R, DRVVT, anti-β2GP1, anti-β2GP1, anti-phosphatidylserine and anti-cardiolipin antibody assays were performed. Results: There was a high prevalence of abnormal A5R despite a low prevalence of antiphospholipid antibodies. Multivariate logistic regression analyses showed an association with silent infarcts (p = 0.015), lower hemoglobin (p = 0.037), older age (p = 0.047) and abnormal A5R. Conclusion: We report an association between annexin A5 resistance and presence of silent infarct, low hemoglobin, and older age in a subgroup of SCA subjects. A potential role for perturbed A5R in the pathophysiology of SCA needs to be evaluated further.",
keywords = "Annexin A5 resistance, Antiphospholipid antibody, Sickle cell disease, Silent infarcts",
author = "Morrone, {Kerry A.} and Pecker, {Lydia H.} and Jacob Rand and Davila, {Jennifer G.} and Oyeku, {Suzette Olu Busola} and Little, {Jane A.} and Xue, {Xiaonan (Nan)} and Manwani, {Deepa G.}",
year = "2017",
doi = "10.1016/j.bcmd.2017.09.001",
language = "English (US)",
journal = "Blood Cells, Molecules, and Diseases",
issn = "1079-9796",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Association of silent infarcts in sickle cell anemia with decreased annexin A5 resistance

AU - Morrone, Kerry A.

AU - Pecker, Lydia H.

AU - Rand, Jacob

AU - Davila, Jennifer G.

AU - Oyeku, Suzette Olu Busola

AU - Little, Jane A.

AU - Xue, Xiaonan (Nan)

AU - Manwani, Deepa G.

PY - 2017

Y1 - 2017

N2 - Background: Sickle cell anemia (SCA) is characterized by abnormally shaped, adhesive RBCs that interact with white blood cells and the endothelium, leading to chronic hemolysis, vasculopathy and a prothrombotic state. About 10% of subjects with a thrombotic event in the general population will have an associated antiphospholipid (aPL) antibody. One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of the potent anticoagulant annexin A5 or Annexin A5 resistance (A5R). We designed a pilot study assessing the presence of aPL antibodies and disruption of A5R in pediatric sickle cell subjects. Methods: 39 subjects with SCA participated in this study. A5R, DRVVT, anti-β2GP1, anti-β2GP1, anti-phosphatidylserine and anti-cardiolipin antibody assays were performed. Results: There was a high prevalence of abnormal A5R despite a low prevalence of antiphospholipid antibodies. Multivariate logistic regression analyses showed an association with silent infarcts (p = 0.015), lower hemoglobin (p = 0.037), older age (p = 0.047) and abnormal A5R. Conclusion: We report an association between annexin A5 resistance and presence of silent infarct, low hemoglobin, and older age in a subgroup of SCA subjects. A potential role for perturbed A5R in the pathophysiology of SCA needs to be evaluated further.

AB - Background: Sickle cell anemia (SCA) is characterized by abnormally shaped, adhesive RBCs that interact with white blood cells and the endothelium, leading to chronic hemolysis, vasculopathy and a prothrombotic state. About 10% of subjects with a thrombotic event in the general population will have an associated antiphospholipid (aPL) antibody. One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of the potent anticoagulant annexin A5 or Annexin A5 resistance (A5R). We designed a pilot study assessing the presence of aPL antibodies and disruption of A5R in pediatric sickle cell subjects. Methods: 39 subjects with SCA participated in this study. A5R, DRVVT, anti-β2GP1, anti-β2GP1, anti-phosphatidylserine and anti-cardiolipin antibody assays were performed. Results: There was a high prevalence of abnormal A5R despite a low prevalence of antiphospholipid antibodies. Multivariate logistic regression analyses showed an association with silent infarcts (p = 0.015), lower hemoglobin (p = 0.037), older age (p = 0.047) and abnormal A5R. Conclusion: We report an association between annexin A5 resistance and presence of silent infarct, low hemoglobin, and older age in a subgroup of SCA subjects. A potential role for perturbed A5R in the pathophysiology of SCA needs to be evaluated further.

KW - Annexin A5 resistance

KW - Antiphospholipid antibody

KW - Sickle cell disease

KW - Silent infarcts

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U2 - 10.1016/j.bcmd.2017.09.001

DO - 10.1016/j.bcmd.2017.09.001

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JF - Blood Cells, Molecules, and Diseases

SN - 1079-9796

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