SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occuring before age 40

Annika M. Svensson; Gordon R. Whiteley; Peter W. Callas; Edwin G. Bovill

doi:10.1160/TH06-05-0273

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(06): 725-730
DOI: 10.1160/TH06-05-0273

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occuring before age 40

Annika M. Svensson^*

¹Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

,

Gordon R. Whiteley

²Clinical Proteomics Reference Lab, SAIC-Frederick, Inc., NCI Frederick, Gaithersburg, Maryland, USA

,

Peter W. Callas

³Department of Biostatistics, University of Vermont College of Medicine, Burlington, Vermont, USA

,

Edwin G. Bovill

¹Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

› Author Affiliations

Abstract

Summary

We tested the hypothesis that differences in the low-molecularweight (500–20,000 Da) proteomic profile of plasma may be detectable between members ofa protein C-deficient family who have suffered thrombotic events before age 40 compared to family members without a history of venous thrombosis. Unfractionated plasma samples from members of a previously described large thrombophilic kindred with type I protein C deficiency were applied to ProteinChip weak cation exchange interaction arrays (WCX2; Ciphergen Biosystems, Fremont, CA, USA) and subjected to SELDI-TOF (surface-enhanced laser desorption/ionization time-of-flight) mass spectrometry using the Ciphergen PBSII ProteinChip System (Ciphergen Biosystems). Profiles were analyzed by a boosted decision-tree algorithm. When individuals who had presented with deep venous thrombosis (DVT) before the age of 40 (n=21) were compared to age-matched, healthy family members (n=50), the proteomic patterns defined by the decision-tree analysis could classify the entity of DVT before age 40 with 67% sensitivity, ata specificity of 86%.Whena small group of cases with history of superficial venous thrombosis (n=6) was added to the case group, the sensitivity was 87.5% at a specificity of 80%.These data support the hypothesis that members of the protein C deficient Vermont kindred II who suffer a thrombotic event before age 40 display significant differences in low-molecular-weight proteomics profile compared to those who remain disease-free.This is the first study to apply SELDI-TOF technology in conjunction with a bioinformatics tool to analyze low-molecular-weight proteomic patterns in patients with venous thrombosis.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U. S. Government.

Keywords

Venous thrombosis - SELDI-TOF - mass spectrometry - proteomics - protein C deficiency

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References

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