Skip to main content
Top
Published in: Indian Journal of Hematology and Blood Transfusion 3/2019

01-07-2019 | Original Article

Elevated Von Willebrand Factor Antigen Levels are an Independent Risk Factor for Venous Thromboembolism: First Report from North India

Authors: Sweta Rajpal, Jasmina Ahluwalia, Narender Kumar, Pankaj Malhotra, Varun Uppal

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 3/2019

Login to get access

Abstract

Elevated levels of coagulation factor VIII have been associated with increased risk for venous thromboembolism (VTE). The role of Von Willebrand factor (VWF) in VTE is unclear. In this study, we investigated the association of raised levels of VWF and factor VIII in patients with VTE. 100 patients of VTE and 100 age and gender matched controls were tested for levels of VWF antigen, coagulation factor VIII:C, Protein C, Protein S, antithrombin, antiphospholipid antibodies and for the presence of Factor V Leiden mutation. The mean level of VWF was significantly higher amongst patients of VTE (177.3 IU/dl) when compared to controls (129.7 IU/dl) (P < 0.001). Similarly, the mean level of FVIII:C was significantly higher amongst patients of VTE (199.1 IU/dl) when compared to controls (145.2 IU/dl) (P < 0.001). On logistic regression analysis, after adjusting for FVIII:C, Protein S, factor V Leiden and trauma, the association of raised VWF with VTE remained significant (P = 0.001). Similarly higher levels of FVIII:C persisted to have an independent association with VTE (P = 0.004). Both, higher levels of VWF and FVIII:C levels, are independently associated with VTE.
Literature
1.
go back to reference Agarwala S, Bhagwat AS, Modhe J (2003) Deep vein thrombosis in Indian patients undergoing major lower limb surgery. Indian J Surg 65:159–162 Agarwala S, Bhagwat AS, Modhe J (2003) Deep vein thrombosis in Indian patients undergoing major lower limb surgery. Indian J Surg 65:159–162
2.
go back to reference Chougule A, Rajpal S, Ahluwalia J et al (2016) Coagulation factor VIII, IX and XI levels in north Indian patients with venous thromboembolism: first study from India. Blood Coagul Fibrinolysis 27:58–63CrossRefPubMed Chougule A, Rajpal S, Ahluwalia J et al (2016) Coagulation factor VIII, IX and XI levels in north Indian patients with venous thromboembolism: first study from India. Blood Coagul Fibrinolysis 27:58–63CrossRefPubMed
4.
go back to reference Bucek RA, Reiter M, Quehenberger P et al (2003) Thrombus precursor protein, endogenous thrombin potential, von-Willebrand factor and activated factor VII in suspected deep vein thrombosis: is there a place for new parameters? Br J Haematol 120:123–128CrossRefPubMed Bucek RA, Reiter M, Quehenberger P et al (2003) Thrombus precursor protein, endogenous thrombin potential, von-Willebrand factor and activated factor VII in suspected deep vein thrombosis: is there a place for new parameters? Br J Haematol 120:123–128CrossRefPubMed
5.
go back to reference Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Doggen CJM (2010) Venous thrombosis of the upper extremity: effect of blood group and coagulation factor levels on risk. Br J Haematol 149:118–123CrossRefPubMed Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Doggen CJM (2010) Venous thrombosis of the upper extremity: effect of blood group and coagulation factor levels on risk. Br J Haematol 149:118–123CrossRefPubMed
6.
go back to reference Hazra D, Sen I, Stephen E et al (2015) Evaluation of factor VIII as a risk factor in Indian patients with DVT. Surg Res Pract 2015:307879PubMedPubMedCentral Hazra D, Sen I, Stephen E et al (2015) Evaluation of factor VIII as a risk factor in Indian patients with DVT. Surg Res Pract 2015:307879PubMedPubMedCentral
7.
go back to reference Koster T, Blann AD, Briët E et al (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345:152–155CrossRefPubMed Koster T, Blann AD, Briët E et al (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345:152–155CrossRefPubMed
8.
go back to reference Kraaijenhagen RA, in’t Anker PS, Koopman MM et al (2000) High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 83:5–9CrossRefPubMed Kraaijenhagen RA, in’t Anker PS, Koopman MM et al (2000) High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 83:5–9CrossRefPubMed
9.
go back to reference O’Donnell J, Tuddenham EG, Manning R et al (1997) High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 77:825–828CrossRefPubMed O’Donnell J, Tuddenham EG, Manning R et al (1997) High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 77:825–828CrossRefPubMed
10.
go back to reference Ota S, Yamada N, Ogihara Y et al (2011) High plasma level of factor VIII: an important risk factor for venous thromboembolism. Circ J 75:1472–1475CrossRefPubMed Ota S, Yamada N, Ogihara Y et al (2011) High plasma level of factor VIII: an important risk factor for venous thromboembolism. Circ J 75:1472–1475CrossRefPubMed
11.
go back to reference Tsai AW, Cushman M, Rosamond WD et al (2002) Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med 113:636–642CrossRefPubMed Tsai AW, Cushman M, Rosamond WD et al (2002) Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med 113:636–642CrossRefPubMed
12.
go back to reference Kamphuisen PW, Eikenboom JC, Rosendaal FR et al (2001) High factor VIII antigen levels increase the risk of venous thrombosis but are not associated with polymorphisms in the von Willebrand factor and factor VIII gene. Br J Haematol 115:156–158CrossRefPubMed Kamphuisen PW, Eikenboom JC, Rosendaal FR et al (2001) High factor VIII antigen levels increase the risk of venous thrombosis but are not associated with polymorphisms in the von Willebrand factor and factor VIII gene. Br J Haematol 115:156–158CrossRefPubMed
13.
go back to reference Karakaya B, Tombak A, Serin MS, Tiftik N (2016) Change in plasma a disintegrin and metalloprotease with thrombospondin type-1 repeats-13 and von Willebrand factor levels in venous thromboembolic patients. Hematology 21:295–299CrossRefPubMed Karakaya B, Tombak A, Serin MS, Tiftik N (2016) Change in plasma a disintegrin and metalloprotease with thrombospondin type-1 repeats-13 and von Willebrand factor levels in venous thromboembolic patients. Hematology 21:295–299CrossRefPubMed
14.
go back to reference Morelli VM, De Visser MCH, Vos HL et al (2005) ABO blood group genotypes and the risk of venous thrombosis: effect of factor V Leiden. J Thromb Haemost 3:183–185CrossRefPubMed Morelli VM, De Visser MCH, Vos HL et al (2005) ABO blood group genotypes and the risk of venous thrombosis: effect of factor V Leiden. J Thromb Haemost 3:183–185CrossRefPubMed
15.
go back to reference Schleef M, Strobel E, Dick A et al (2005) Relationship between ABO and Secretor genotype with plasma levels of factor VIII and von Willebrand factor in thrombosis patients and control individuals. Br J Haematol 128:100–107CrossRefPubMed Schleef M, Strobel E, Dick A et al (2005) Relationship between ABO and Secretor genotype with plasma levels of factor VIII and von Willebrand factor in thrombosis patients and control individuals. Br J Haematol 128:100–107CrossRefPubMed
16.
go back to reference Muellner SK, Haut ER, Streiff MB et al (2010) ABO blood group as a potential risk factor for venous thromboembolism in acutely injured patients. Thromb Haemost 105:5–13CrossRefPubMed Muellner SK, Haut ER, Streiff MB et al (2010) ABO blood group as a potential risk factor for venous thromboembolism in acutely injured patients. Thromb Haemost 105:5–13CrossRefPubMed
17.
go back to reference Gallinaro L, Cattini MG, Sztukowska M et al (2008) A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood 111:3540–3545CrossRefPubMed Gallinaro L, Cattini MG, Sztukowska M et al (2008) A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood 111:3540–3545CrossRefPubMed
18.
go back to reference O’Donnell J, Boulton FE, Manning RA, Laffan MA (2002) Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels. Arterioscler Thromb Vasc Biol 22:335–341CrossRefPubMed O’Donnell J, Boulton FE, Manning RA, Laffan MA (2002) Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels. Arterioscler Thromb Vasc Biol 22:335–341CrossRefPubMed
19.
go back to reference O’Donnell J, Laffan MA (2001) The relationship between ABO histo-blood group, factor VIII and von Willebrand factor. Transfus Med 11:343–351CrossRefPubMed O’Donnell J, Laffan MA (2001) The relationship between ABO histo-blood group, factor VIII and von Willebrand factor. Transfus Med 11:343–351CrossRefPubMed
20.
go back to reference Nilsson T, Mellbring G, Hedner U (1986) Relationship between factor XII, von Willebrand factor and postoperative deep vein thrombosis. Acta Chir Scand 152:347–349PubMed Nilsson T, Mellbring G, Hedner U (1986) Relationship between factor XII, von Willebrand factor and postoperative deep vein thrombosis. Acta Chir Scand 152:347–349PubMed
21.
go back to reference van Schie MC, van Loon JE, de Maat MPM, Leebeek FWG (2011) Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review. J Thromb Haemost 9:899–908CrossRefPubMed van Schie MC, van Loon JE, de Maat MPM, Leebeek FWG (2011) Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review. J Thromb Haemost 9:899–908CrossRefPubMed
22.
go back to reference Calabrò P, Gragnano F, Golia E, Grove EL (2018) von Willebrand factor and venous thromboembolism: pathogenic link and therapeutic implications. Semin Thromb Hemost 44:249–260CrossRefPubMed Calabrò P, Gragnano F, Golia E, Grove EL (2018) von Willebrand factor and venous thromboembolism: pathogenic link and therapeutic implications. Semin Thromb Hemost 44:249–260CrossRefPubMed
23.
go back to reference Machlus KR, Colby EA, Wu JR et al (2009) Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram. Thromb Haemost 102:936–944CrossRefPubMedPubMedCentral Machlus KR, Colby EA, Wu JR et al (2009) Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram. Thromb Haemost 102:936–944CrossRefPubMedPubMedCentral
24.
go back to reference Ryland JK, Lawrie AS, Mackie IJ, Machin SJ (2012) Persistent high factor VIII activity leading to increased thrombin generation—a prospective cohort study. Thromb Res 129:447–452CrossRefPubMed Ryland JK, Lawrie AS, Mackie IJ, Machin SJ (2012) Persistent high factor VIII activity leading to increased thrombin generation—a prospective cohort study. Thromb Res 129:447–452CrossRefPubMed
25.
go back to reference De Mitrio V, Marino R, Scaraggi FA et al (1999) Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation. Blood Coagul Fibrinolysis 10:409–416PubMed De Mitrio V, Marino R, Scaraggi FA et al (1999) Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation. Blood Coagul Fibrinolysis 10:409–416PubMed
26.
go back to reference Shen W, Gu Y, Zhu R et al (2013) Copy number variations of the F8 gene are associated with venous thromboembolism. Blood Cells Mol Dis 50:259–262CrossRefPubMed Shen W, Gu Y, Zhu R et al (2013) Copy number variations of the F8 gene are associated with venous thromboembolism. Blood Cells Mol Dis 50:259–262CrossRefPubMed
27.
go back to reference Mansvelt EP, Laffan M, McVey JH, Tuddenham EG (1998) Analysis of the F8 gene in individuals with high plasma factor VIII:C levels and associated venous thrombosis. Thromb Haemost 80:561–565PubMed Mansvelt EP, Laffan M, McVey JH, Tuddenham EG (1998) Analysis of the F8 gene in individuals with high plasma factor VIII:C levels and associated venous thrombosis. Thromb Haemost 80:561–565PubMed
Metadata
Title
Elevated Von Willebrand Factor Antigen Levels are an Independent Risk Factor for Venous Thromboembolism: First Report from North India
Authors
Sweta Rajpal
Jasmina Ahluwalia
Narender Kumar
Pankaj Malhotra
Varun Uppal
Publication date
01-07-2019
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 3/2019
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-019-01092-y

Other articles of this Issue 3/2019

Indian Journal of Hematology and Blood Transfusion 3/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine