Reduction of annexin A5 anticoagulant ratio identifies antiphospholipid antibody-positive patients with adverse clinical outcomes

Lucia R. Wolgast, A. A. Arslan, X. X. Wu, J. N. Beyda, V. Pengo, J. H. Rand

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Essentials: Annexin A5 resistance is a mechanism for antiphospholipid (aPL) syndrome. 750 patients with history of thrombosis, pregnancy complications and controls were tested. Reduced annexin A5 anticoagulant ratios (A5R) correlate with aPL antibody multipositivity. Reduced A5R may identify patients with a propensity for thrombosis or pregnancy complications. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini Summary: Background: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with annexin A5 crystallization and anticoagulant activity. Objective: The purpose of this study was to investigate whether reduced values in the annexin A5 anticoagulant ratio (A5R) assay (i.e. 'annexin A5 resistance') are associated with adverse clinical events in aPL antibody-positive patients. Patients/Methods: In an initial discovery phase, a group of 679 patient samples from a 'real-world' tertiary care hospital population were tested for A5R. This was followed by a validation-phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history of an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. Results: In the discovery-phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared with aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery-phase group and validation-phase cohort correlated with the extent of multi-positivity for standard APS tests, which has also been shown to be associated with a risk of adverse clinical outcomes. Conclusion: Reduced A5R values were associated with a multi-positivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events.

Original languageEnglish (US)
JournalJournal of Thrombosis and Haemostasis
DOIs
StateAccepted/In press - 2017

Fingerprint

Antiphospholipid Antibodies
Annexin A5
Anticoagulants
Antiphospholipid Syndrome
Pregnancy Complications
Thrombosis
Tertiary Healthcare
Crystallization
Tertiary Care Centers
Phospholipids

Keywords

  • Annexin A5
  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Pregnancy complications
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Reduction of annexin A5 anticoagulant ratio identifies antiphospholipid antibody-positive patients with adverse clinical outcomes. / Wolgast, Lucia R.; Arslan, A. A.; Wu, X. X.; Beyda, J. N.; Pengo, V.; Rand, J. H.

In: Journal of Thrombosis and Haemostasis, 2017.

Research output: Contribution to journalArticle

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abstract = "Essentials: Annexin A5 resistance is a mechanism for antiphospholipid (aPL) syndrome. 750 patients with history of thrombosis, pregnancy complications and controls were tested. Reduced annexin A5 anticoagulant ratios (A5R) correlate with aPL antibody multipositivity. Reduced A5R may identify patients with a propensity for thrombosis or pregnancy complications. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini Summary: Background: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with annexin A5 crystallization and anticoagulant activity. Objective: The purpose of this study was to investigate whether reduced values in the annexin A5 anticoagulant ratio (A5R) assay (i.e. 'annexin A5 resistance') are associated with adverse clinical events in aPL antibody-positive patients. Patients/Methods: In an initial discovery phase, a group of 679 patient samples from a 'real-world' tertiary care hospital population were tested for A5R. This was followed by a validation-phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history of an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. Results: In the discovery-phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared with aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery-phase group and validation-phase cohort correlated with the extent of multi-positivity for standard APS tests, which has also been shown to be associated with a risk of adverse clinical outcomes. Conclusion: Reduced A5R values were associated with a multi-positivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events.",
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AU - Wolgast, Lucia R.

AU - Arslan, A. A.

AU - Wu, X. X.

AU - Beyda, J. N.

AU - Pengo, V.

AU - Rand, J. H.

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N2 - Essentials: Annexin A5 resistance is a mechanism for antiphospholipid (aPL) syndrome. 750 patients with history of thrombosis, pregnancy complications and controls were tested. Reduced annexin A5 anticoagulant ratios (A5R) correlate with aPL antibody multipositivity. Reduced A5R may identify patients with a propensity for thrombosis or pregnancy complications. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini Summary: Background: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with annexin A5 crystallization and anticoagulant activity. Objective: The purpose of this study was to investigate whether reduced values in the annexin A5 anticoagulant ratio (A5R) assay (i.e. 'annexin A5 resistance') are associated with adverse clinical events in aPL antibody-positive patients. Patients/Methods: In an initial discovery phase, a group of 679 patient samples from a 'real-world' tertiary care hospital population were tested for A5R. This was followed by a validation-phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history of an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. Results: In the discovery-phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared with aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery-phase group and validation-phase cohort correlated with the extent of multi-positivity for standard APS tests, which has also been shown to be associated with a risk of adverse clinical outcomes. Conclusion: Reduced A5R values were associated with a multi-positivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events.

AB - Essentials: Annexin A5 resistance is a mechanism for antiphospholipid (aPL) syndrome. 750 patients with history of thrombosis, pregnancy complications and controls were tested. Reduced annexin A5 anticoagulant ratios (A5R) correlate with aPL antibody multipositivity. Reduced A5R may identify patients with a propensity for thrombosis or pregnancy complications. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini Summary: Background: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with annexin A5 crystallization and anticoagulant activity. Objective: The purpose of this study was to investigate whether reduced values in the annexin A5 anticoagulant ratio (A5R) assay (i.e. 'annexin A5 resistance') are associated with adverse clinical events in aPL antibody-positive patients. Patients/Methods: In an initial discovery phase, a group of 679 patient samples from a 'real-world' tertiary care hospital population were tested for A5R. This was followed by a validation-phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history of an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. Results: In the discovery-phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared with aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery-phase group and validation-phase cohort correlated with the extent of multi-positivity for standard APS tests, which has also been shown to be associated with a risk of adverse clinical outcomes. Conclusion: Reduced A5R values were associated with a multi-positivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events.

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KW - Pregnancy complications

KW - Thrombosis

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