Type and Location of Venous Thromboembolism in Carriers of Factor V Leiden or Prothrombin G20210A Mutation Versus Patients With No Mutation

Abstract

Factor V Leiden (FVLeiden) and prothrombin G20210A are the most common genetic causes of thrombophilia and established risk factors for different clinical manifestations of venous thromboembolism (VTE). This study investigated whether the clinical manifestation of VTE, the extension of deep vein thrombosis (DVT) and the presence of transient risk factors at the time of the first VTE, differed among patients with mutations (97 with FVLeiden; 33 with prothrombin G20210A) and in 109 patients without thrombophilia. Isolated pulmonary embolism (PE) was less prevalent in patients with FVLeiden (6%) and no thrombophilia (6%) than in those with prothrombin G20210A (15%). No difference was found in the incidence of distal DVT. Regarding the extension of proximal DVT, the lowest incidence for isolated popliteal vein and the highest for iliofemoral vein were observed in patients with prothrombin G20210A. No difference was observed between groups of patients with or without thrombophilia by unprovoked VTE. The pregnancy/puerperium was the most prevalent risk factor in carriers of prothrombin G20210A. Among FVLeiden carriers, the most prevalent risk factor was surgery, and in patients without thrombophilia, it was trauma (P < .05). Thrombosis of the upper limb was more frequent in a group without thrombophilia than in patients with mutations (P < .01). Transverse sinus venous thrombosis was present only in patients with prothrombin G20210A. Carriers of prothrombin G20210A have an increased risk of developing isolated PE and more severe clinical manifestations than those with FVLeiden or without thrombophilia.

Keywords

factor V Leiden prothrombin G20210A venous thromboembolism clinical manifestations isolated PE

References

Rosendaal FR Risk factors for venous thrombotic disease . Thromb Haemost. 1999;82:610-619.

Bertina RM Genetic approach to thrombophilia. Thromb Haemost . 2001;86:92-103.

Dahlbäck B. Resistance to activated protein C caused by the Factor VR506Q mutation is a common risk factor for venous thrombosis. Thromb Haemost. 1997;78:483-488.

Poort SR , Rosendal FR , Reitsma PH , Bertina RM A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698-3703.

Martinelli I. , Bottasso B. , Duca F. , Faioni E. , Mannucci PM Heightened thrombin generation in individuals with resistance to activated protein C . Thromb Haemost. 1996;75:703-705.

Janssen HL , Meinardi JR , Vleggaar FP , et al. Factor V Leiden mutation, prothrombin gene mutation and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood. 2000;96:2364-2368.

Manten B. , Westendorp RG , Koster T. , Reitsma PH , Rosendaal FR Risk factor profiles in patients with different clinical manifestations of venous thromboembolis: a focus on the factor V Leiden mutation. Thromb Haemost. 1996;76:510-513.

Martinelli I. , Cattaneo M. , Panzeri D. , Mannucci PM Low prevalence of factor V:Q506 in 41 patients with isolated pulmonary embolism. Thromb Haemost 1997;77: 440-443.

Bounameaux H. Factor V Leiden paradox: risk of deep vein thrombosis but not of pulmonary embolism. Lancet. 2000 ;356:182-183.

10.

Margaglione M. , Brancaccio V. , De Lucia D. , et al. Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism. Chest. 2000;118: 1405-1411.

11.

Kovac M. , Mikovic D. , Antonijevic N. , et al. FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian population. J Thromb Thrombolysis. 2008;25: 284-287.

12.

Kovac M. , Mikovic D. , Antonijevic N. , et al. Risk of recurrent venous thromboembolism in patients with deep vein thrombosis who are carriers of the Factor V Leiden or prothrombin gene mutation. Pathophysiol Haemost Thromb. 2006 ;35:P-1067.

13.

Djordjevic V. , Rakicevic LJ , Spasic M. , et al. FV Leiden, FII G20210A, MTHFR C677T mutations and first venous thrombosis during pregnancy and puerperioum. Vojnosanit Pregl. 2004;62:201.

14.

Martinelli I. , Battaglioli T. , Razzari C. , Mannucci PM Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombopholia. J Thromb Haemost . 2007;5:98-101.

15.

Emmerich J. , Rosendaal FR , Cattaneo M. , et al. Combined effect of factor V Leiden and prothrombin 20210 A on the risk of venous thromboembolism-pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost . 2001;86:809-816; erratum 1598.

16.

de Moerloose P. , Reber G. , Perrier A. , Perneger T. , Bounameaux H. Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism. Br J Haematol. 2000;110: 125-129.

17.

Wåhlander K. , Larson G. , Lindahl TL , et al. Factor V Leiden (G169A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery. Thromb Haemost. 2002;87:580-585.

18.

Schulman S. Thrombophilia and location of venous thromboembolism . J Thromb Haemost. 2007;5:2151-2152.

19.

Björgell O. , Nilsson PE , Nilsson JA , Svensson PJ Location and extent of deep vein thrombosis in patients with and without FV:R 506Q Mutation . Thromb Haemost . 2000;83:648-651.

20.

Huisman MV , Klok FA , Karami Djurabi R. , Tormene D. , Simioni P. , Prandoni P. Factor V Leiden is associated with more distal location of deep vein thrombosis in the leg. J Thromb Haemost. 2008 ;6:544-545.

21.

Prandoni P. , Polistena P. , Bernardi E. , et al. Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med. 1997;157:57-62.

22.

Martinelli I. , Cattaneo M. , Panzeri D. , Taioli E. , Mannucci PM Risk factors for deep venous thrombosis of the upper extremities. Ann Intern Med. 1997 ;126:707-711.

23.

Legnani C. , Cosmi B. , Valdrè L. , et al. Venous thromboembolism, oral contraceptives and high prothrombin levels. J Thromb Haemost. 2003;1:112-117.

24.

Martinelli I. , Sacchi E. , Landi G. , Taioli E. , Duca F. , Mannucci PM High risk of cerebral-vein thrombosis in carriers of prothrombin gene mutation and in users of oral contraceptives. N Engl J Med. 1998 ;338:1793-1797.