Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia

A study of 150 families

Ida Martinelli, Pier Mannuccio Mannucci, Valerio De Stefano, Emanuela Taioli, Valentina Rossi, Francesca Crosti, Katia Paciaroni, Giuseppe Leone, Elena M. Faioni

Research output: Contribution to journalArticle

352 Citations (Scopus)

Abstract

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3.5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

Original languageEnglish
Pages (from-to)2353-2358
Number of pages6
JournalBlood
Volume92
Issue number7
Publication statusPublished - Oct 1 1998

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Thrombophilia
Coagulation
Thrombosis
Protein C
Protein S
Defects
Protein S Deficiency
Confidence Intervals
Antithrombin Proteins
Antithrombins
Veins
Venous Thrombosis
Activated Protein C Resistance
factor V Leiden
Venous Thromboembolism
Anticoagulants
Pulmonary Embolism
Causality
Genes
Odds Ratio

ASJC Scopus subject areas

  • Hematology

Cite this

Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia : A study of 150 families. / Martinelli, Ida; Mannucci, Pier Mannuccio; De Stefano, Valerio; Taioli, Emanuela; Rossi, Valentina; Crosti, Francesca; Paciaroni, Katia; Leone, Giuseppe; Faioni, Elena M.

In: Blood, Vol. 92, No. 7, 01.10.1998, p. 2353-2358.

Research output: Contribution to journalArticle

Martinelli, I, Mannucci, PM, De Stefano, V, Taioli, E, Rossi, V, Crosti, F, Paciaroni, K, Leone, G & Faioni, EM 1998, 'Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: A study of 150 families', Blood, vol. 92, no. 7, pp. 2353-2358.
Martinelli, Ida ; Mannucci, Pier Mannuccio ; De Stefano, Valerio ; Taioli, Emanuela ; Rossi, Valentina ; Crosti, Francesca ; Paciaroni, Katia ; Leone, Giuseppe ; Faioni, Elena M. / Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia : A study of 150 families. In: Blood. 1998 ; Vol. 92, No. 7. pp. 2353-2358.
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abstract = "Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95{\%} confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95{\%} CI, 2.9 to 18.4) or protein S deficiency (8.5, 95{\%} CI, 3.5 to 20.8), and factor V Leiden (2.2, 95{\%} CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95{\%} CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95{\%} CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90{\%} in antithrombin, 88{\%} in protein C, 100{\%} in protein S deficiency, and 57{\%} in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43{\%}). There was a predisposing factor at the time of venous thromboembolism in approximately 50{\%} of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.",
author = "Ida Martinelli and Mannucci, {Pier Mannuccio} and {De Stefano}, Valerio and Emanuela Taioli and Valentina Rossi and Francesca Crosti and Katia Paciaroni and Giuseppe Leone and Faioni, {Elena M.}",
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AU - Taioli, Emanuela

AU - Rossi, Valentina

AU - Crosti, Francesca

AU - Paciaroni, Katia

AU - Leone, Giuseppe

AU - Faioni, Elena M.

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N2 - Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3.5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

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