Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S.
Many subjects carrying inherited thrombophilic defects will never experience venous thromboembolism (VTE) while other individuals developed recurrent VTE with no known additional risk factors. High levels of circulating microparticles (MP) have been associated with increased risk of VTE in patients with factor V Leiden and prothrombin G20210A mutation, suggesting a possible contribution of MP in the hypercoagulability of mild genetic thrombophilia. The role of MP as additional risk factor of VTE in carriers of natural clotting inhibitors defects (severe thrombophilia) has never been assessed. Plasma levels of annexin V-MP, endothelial-derived MP (EMP), platelet-derived MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) were measured in 132 carriers of natural anticoagulant deficiencies (25 antithrombin, 63 protein C and 64 protein S defect) and in 132 age and gender-matched healthy controls. Carriers of natural anticoagulant deficiencies, overall and separately considered, presented with higher median levels of annexin V-MP, EMP, PMP, TF+MP and PPL activity than healthy controls (p< 0.001, < 0.001, < 0.01, 0.025 and 0.03, respectively). Symptomatic carriers with a previous episode of VTE had significantly higher median levels of annexin-V MP than those without VTE (p=0.027). Carriers with high levels of annexin V-MP, EMP and PMP had an adjusted OR for VTE of 3.36 (95% CI, 1.59 to 7.11), 9.26 (95% CI, 3.55 to 24.1) and 2.72 (95%CI, 1.16 to 6.38), respectively. Elevated levels of circulating MP can play a role in carriers of mild and severe inherited thrombophilia. The clinical implications of this association remain to be defined.
Elena
E
Campello
Luca
L
Spiezia
Claudia M
CM
Radu
Cristiana
C
Bulato
Sabrina
S
Gavasso
Daniela
D
Tormene
Barry
B
Woodhams
Fabio
F
Dalla Valle
Paolo Simioni, MD, PhD, 5th Chair of Internal Medicine, Thrombophilia and Hemophilia Center, Department of Medicine, University of Padua, Via Ospedale Civile 105, 35100 Padua, Italy, Tel.: +39 049 8212667, Fax: +39 049 8212651, E-mail: paolo.simioni@unipd.it.
Paolo
P
Simioni
D000328:Adult; D020152:Antithrombin III Deficiency / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020151:Protein C Deficiency / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D018455:Protein S Deficiency / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D054556:Venous Thromboembolism / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
Coagulation inhibitors; hypercoagulability; microparticles; thrombophilia; venous thrombosis