Surface-Enhanced Laser Desorption/Ionization Mass Spectral Plasma Profiles Distinguish Individuals of a Protein C-Deficient Family with a Thrombotic Episode before the Age of 40 from Age-Matched Family Members without a History of Thrombosis.

We tested the hypothesis that differences in the low molecular weight (500–20.000 Da) proteomic profile of plasma may be detectable between members of a protein C-deficient thrombophilic 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 chips (WCX2; Ciphergen Biosystems, Fremont, CA) and subjected to SELDI-TOF (surface-enhanced laser desorption/ionization time-of-flight) mass spectrometry using the Ciphergen PBSII ProteinChip System (Ciphergen Biosystems, Freemont, CA, USA). Profiles were analyzed by a boosted decision-tree algorithm. When individuals who had presented with deep venous thrombosis 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 66% sensitivity, at a specificity of 86%. When a 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. We are presently pursuing higher resolution analysis with the prOTOF, MALDI orthogonal time of flight mass spectrometer system in order to identify specific peptides