Highlights & Basics
- Hypercoagulable state (also known as prothrombotic state or thrombophilia) is the propensity to venous thrombosis due to an abnormality in the coagulation system.
- It may be inherited or acquired, although in some cases the underlying cause cannot be identified.
- Many factors contribute to the hypercoagulable state. Inherited thrombophilia affects up to 10% of the population; acquired risk factors, such as obesity and hormonal therapy, are frequent in the community.
- Most patients with heritable thrombophilia remain asymptomatic.
- Venous thromboembolism is the most common manifestation of the hypercoagulable state. It can be prevented in some patients through identification of those at risk and appropriate thromboprophylaxis during periods of high risk, such as admission to the hospital and following major surgery.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e691S-736S.[Abstract][Full Text]
American College of Chest Physicians. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST. 2012;141(suppl 2):e1S-801S.[Full Text]
Arachchillage DJ, Mackillop L, Chandratheva A, et al. Thrombophilia testing: A British Society for Haematology guideline. Br J Haematol. 2022 Aug;198(3):443-58.[Abstract][Full Text]
Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-944.[Abstract][Full Text]
Key NS, Khorana AA, Kuderer NM, et al. Venous Thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023 Jun 1;41(16):3063-71.[Abstract][Full Text]
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cancer-associated venous thromboembolic disease [internet publication].[Full Text]
1. The British Committee for Standards in Haematology. Guidelines on the investigation and management of thrombophilia. J Clin Pathol. 1990 Sep;43(9):703-9.[Abstract][Full Text]
2. Kitchens CS. Concept of hypercoagulability: a review of its development, clinical application, and recent development. Semin Thromb Hemost. 1985 Jul;11(3):293-315.[Abstract]
3. Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med. 2003 Jan 21;138(2):128-34.[Abstract]
4. Rodger MA, Paidas M, McLintock C, et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol. 2008 Aug;112(2 Pt 1):320-4.[Abstract]
5. Ridker PM, Hennekens CH, Lindpaintner K, et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. N Engl J Med. 1995 Apr 6;332(14):912-7.[Abstract]
6. Poort SR, Rosendaal FR, Reitsma PH, et al. 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 Nov 15;88(10):3698-703.[Abstract][Full Text]
7. Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet. 1995 Oct 28;346(8983):1133-4.[Abstract]
8. Dilley A, Austin H, Hooper WC, et al. Prevalence of the prothrombin 20210 G-to-A variant in blacks: infants, patients with venous thrombosis, patients with myocardial infarction and control subjects. J Lab Clin Med. 1998 Dec;132(6):452-5.[Abstract]
9. Dowling NF, Austin H, Dilley A, et al. The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE study. J Thromb Haemost. 2003 Jan;1(1):80-7.[Abstract]
10. Franco RF, Reitsma PH. Genetic risk factors of venous thrombosis. Hum Genet. 2001 Oct;109(4):369-84.[Abstract]
11. Sakata T, Okamoto A, Mannami T, et al. Protein C and antithrombin deficiency are important risk factors for deep vein thrombosis in Japanese. J Thromb Haemost. 2004 Mar;2(3):528-30.[Abstract]
12. Sakata T, Okamoto A, Mannami T, et al. Prevalence of protein S deficiency in the Japanese general population: the Suita study. J Thromb Haemost. 2004 Jun;2(6):1012-3.[Abstract]
13. Shen MC, Lin JS, Tsay W. High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan. Thromb Res. 1997 Aug 15;87(4):377-85.[Abstract]
14. Patel RK, Ford E, Thumpston J, et al. Risk factors for venous thrombosis in the black population. Thromb Haemost. 2003 Nov;90(5):835-8.[Abstract]
15. Tait RC, Walker ID, Perry DJ, et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol. 1994 May;87(1):106-12.[Abstract]
16. Miyata T, Kimura R, KoburaY, et al. Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K196E mutation. Int J Hematol. 2006 Apr;83(3):217-23.[Abstract]
17. Rosendaal FR. Risk factors for venous thrombotic disease. Thromb Haemost. 1999 Aug;82(2):610-9.[Abstract]
18. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost. 1995 Jan;73(1):87-93.[Abstract]
19. Suehisa E, Nomara T, Kawasaki T, et al. Frequency of natural coagulation inhibitor (antithrombin III, protein C and protein S) deficiencies in Japanese patients with spontaneous deep vein thrombosis. Blood Coagul Fibrinolysis. 2001 Mar;12(2):95-9.[Abstract]
20. Seligsohn U, Berger A, Abend M, et al. Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med. 1984 Mar 1;310(9):559-62.[Abstract]
21. Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008 Nov;14(6):1151-8.[Abstract]
22. Rosendaal FR, Koster T, Vandenbroucke JP, et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood. 1995 Mar 15;85(6):1504-8.[Abstract][Full Text]
23. Heit JA, Beckman MG, Bockenstedt PL, et al. Comparison of characteristics from white- and black-Americans with venous thromboembolism: a cross-sectional study. Am J Hematol. 2010 Jul;85(7):467-71.[Abstract]
24. Lensen R, Rosendaal F, Vandenbroucke J, et al. Factor V Leiden: the venous thrombotic risk in thrombophilic families. Br J Haematol. 2000 Sep;110(4):939-45.[Abstract]
25. Rees DC, Chapman NH, Webster MT, et al. Born to clot: the European burden. Br J Haematol. 1999 May;105(2):564-6.[Abstract]
26. Emmerich J, Rosendaal FR, Cattaneo M, et al; Study Group for Pooled-Analysis in Venous Thromboembolism. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism - pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Thromb Haemost. 2001 Sep;86(3):809-16. [Erratum in: Thromb Haemost. 2001 Dec;86(6):1598.][Abstract]
27. Ataga KI, Key NS. Hypercoagulability in sickle cell disease: a new approach to an old problem. Hematology Am Soc Hematol Educ Program. 2007:91-6.[Abstract][Full Text]
28. Stein PD, Beemath A, Meyers FA, et al. Deep venous thrombosis and pulmonary embolism in hospitalized patients with sickle cell disease. Am J Med. 2006 Oct;119(10):897.e7-11.[Abstract]
29. van Hylckama Vlieg A, Rosendaal FR. High levels of fibrinogen are associated with the risk of deep venous thrombosis mainly in the elderly. J Thromb Haemost. 2003 Dec;1(12):2677-8.[Abstract]
30. Uitte de Willige S, de Visser MC, Houwing-Duistermaat JJ, et al. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood. 2005 Dec 15;106(13):4176-83.[Abstract][Full Text]
31. Koster T, Blann AD, Briet E, et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995 Jan 21;345(8943):152-5.[Abstract]
32. Kraaijenhagen RA, in't Anker PS, Koopman MM, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost. 2000 Jan;83(1):5-9.[Abstract]
33. Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med. 2000 Aug 17;343(7):457-62.[Abstract]
34. van Hylckama Vlieg A, van der Linden IK, Bertina RM, et al. High levels of factor IX increase the risk of venous thrombosis. Blood. 2000 Jun 15;95(12):3678-82.[Abstract][Full Text]
35. Meijers JCM, Tekelenberg WL, Bouma BM, et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000 Mar 9;342(10):696-701.[Abstract][Full Text]
36. Eichinger S, Schönauer V, Weltermann A, et al. Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism. Blood. 2004 May 15;103(10):3773-6.[Abstract][Full Text]
37. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost. 2005 Feb;3(2):292-9.[Abstract]
38. Bezemer ID, Doggen CJM, Vos HL, et al. No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA Study. Arch Intern Med. 2007 Mar 12;167(5):497-501.[Abstract]
39. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998 Mar 23;158(6):585-93.[Abstract]
40. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian registry of VTE. Blood. 1994 Mar 1;83(5):1251-7.[Abstract]
41. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT study. Arch Intern Med. 1991 May;151(5):933-8.[Abstract]
42. Mari D, Mannucci PM, Coppola R, et al. Hypercoagulability in centenarians: the paradox of successful aging. Blood. 1995 Jun 1;85(11):3144-9.[Abstract]
43. Heit JA, Kobbervig CE, James AH, et al. Trends in the incidence of venous thromboembolism during pregnancy or post-partum: a 30 year population-based study. Ann Intern Med. 2005 Nov 15;143(10):697-706.[Abstract]
44. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e691S-736S.[Abstract][Full Text]
45. American College of Chest Physicians. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST. 2012;141(suppl 2):e1S-801S.[Full Text]
46. Blomback M, Konkle BA, Manco-Johnson MJ, et al. Preanalytical conditions that affect coagulation testing, including hormonal status and therapy. J Thromb Haemost. 2007 Apr;5(4):855-8.[Abstract]
47. Berg CJ, Callaghan WM, Syverson C, et al. Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol. 2010 Dec;116(6):1302-9.[Abstract]
48. Knight M, Bunch K, Tuffnell D, et al (eds); on behalf of MBRRACE-UK. Saving lives improving mothers' care - lessons learned to inform maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2014-16. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2018.[Full Text]
49. Heit JA, O'Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism. Arch Intern Med. 2002 Jun 10;162(11):1245-8.[Abstract]
50. Trujillo-Santos J, Prandoni P, Rivron-Guillot K, et al. Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry. J Thromb Haemost. 2008 Feb;6(2):251-5.[Abstract]
51. Rodrigues CA, Ferrarotto R, Kalil Filho R, et al. Venous thromboembolism and cancer: a systematic review. J Thromb Thrombolysis. 2010 Jul;30(1):67-78.[Abstract]
52. Caine GJ, Stonelake PS, Lip GY, et al. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002 Nov-Dec;4(6):465-73.[Abstract]
53. Carrier M, Le Gal G, Wells PS, et al. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008 Sep 2;149(5):323-33.[Abstract]
54. White RH, Chew HK, Zhou H, et al. Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults. Arch Intern Med. 2005 Aug 8-22;165(15):1782-7.[Abstract]
55. Cohen AT, Alikhan R, Arcelus JI, et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost. 2005 Oct;94(4):750-9.[Abstract]
56. Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost. 2004 Dec;2(12):2156-61.[Abstract]
57. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med. 2000 Dec 11-25;160(22):3415-20.[Abstract][Full Text]
58. Bernstein CN, Blanchard JF, Houston DS, et al. The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost. 2001 Mar;85(3):430-4.[Abstract]
59. Farmer-Boatwright MK, Roubey RA. Venous thrombosis in the antiphospholipid syndrome. Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):321-5.[Abstract]
60. Ginsburg KS, Liang MH, Newcomer L, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992 Dec 15;117(12):997-1002.[Abstract]
61. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306.[Abstract][Full Text]
62. Pengo V, Tripodi A, Reber G, et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost. 2009 Oct;7(10):1737-40.[Abstract][Full Text]
63. Arachchillage DRJ, Gomez K, Alikhan R, et al. Addendum to British Society for Haematology guidelines on investigation and management of antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47-58): use of direct acting oral anticoagulants. Br J Haematol. 2020 Apr;189(2):212-5.[Abstract][Full Text]
64. Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005 Feb;128(3):275-90.[Abstract]
65. Hexner EO. JAK2 V617F: implications for thrombosis in myeloproliferative diseases. Curr Opin Hematol. 2007 Sep;14(5):450-4.[Abstract]
66. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006 Dec 7;355(23):2452-66.[Abstract]
67. Mahmoodi BK, ten Kate MK, Waanders F, et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation. 2008 Jan 15;117(2):224-30.[Abstract][Full Text]
68. Singhal R, Brimble KS, Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res. 2006;118(3):397-407.[Abstract]
69. Houman MH, Ben Gourbel I, Ben Salah IK, et al. Deep vein thrombosis in Behcet's disease. Clin Exp Rheumatol. 2001 Sep-Oct;19(5 Suppl 24):S48-50.[Abstract]
70. Espinosa G, Font J, Tassies D, et al. Vascular involvement in Behcet's disease: relation with thrombophilic factors, coagulation activation, and thrombomodulin. Am J Med. 2002 Jan;112(1):37-43.[Abstract]
71. Levi M, Toh CH, Thachil J, et al. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009 Apr;145(1):24-33.[Abstract]
72. Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal haemoglobinuria. New Engl J Med. 1995 Nov 9;333(19):1253-8.[Abstract][Full Text]
73. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007 May;137(3):181-92.[Abstract]
74. Warkentin T, Hayward CP, Boshkov LK, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood. 1994 Dec 1;84(11):3691-9.[Abstract]
75. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e495S-530S.[Abstract][Full Text]
76. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-92.[Abstract][Full Text]
77. Jang, IK, Hursting MJ. When heparins promote thrombosis: review of heparin-induced thrombocytopenia. Circulation. 2005 May 24;111(20):2671-83.[Abstract][Full Text]
78. Rosendaal FR, van Hylckama Vlieg A, Tanis BC, et al. Estrogens, progestogens and thrombosis. J Thromb Haemost. 2003 Jul;1(7):1371-80.[Abstract]
79. Cosman F, Lindsay R. Selective estrogen receptor modulators: clinical spectrum. Endocr Rev. 1999 Jun;20(3):418-34.[Abstract]
80. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med. 2001 May 17;344(20):1527-35.[Abstract]
81. Wu O, Robertson L, Langhorne P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and the risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost. 2005 Jul;94(1):17-25.[Abstract]
82. Cosman F, Baz-Hecht M, Cushman M, et al. Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature. Thromb Res. 2005;116(1):1-13.[Abstract]
83. Eilertsen AL, Sandvik L, Mowinckel MC, et al. Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis. Thromb Res. 2007;120(3):371-9.[Abstract]
84. van Baal WM, Emeis JJ, van der Mooren MJ, et al. Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study. Thromb Haemost. 2000 Jan;83(1):29-34.[Abstract]
85. Canonico M, Plu-Bureau G, Lowe GD, et al. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008 May 20;336(7655):1227-31.[Abstract][Full Text]
86. Cobin RH, Goodman NF, AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology (ACE) position statement on menopause - 2017 update. Endocr Pract. 2017 Jul;23(7):869-80.[Abstract][Full Text]
87. National Institute for Health and Care Excellence. Menopause: diagnosis and management. December 2019 [internet publication].[Full Text]
88. Deitcher SR, Gomes MP. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review. Cancer. 2004 Aug 1;101(3):439-49.[Abstract][Full Text]
89. Garber JE, Halabi S, Tolaney SM, et al. Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer. J Natl Cancer Inst. 2010 Jul 7;102(13):942-9.[Abstract][Full Text]
90. Palumbo A, Rajkumar SV, Dimopoulos MA, et al; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb;22(2):414-23.[Abstract]
91. De Stefano V, Sora F, Rossi E, et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost. 2005 Sep;3(9):1985-92.[Abstract]
92. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(suppl 2):e278S-325.[Abstract][Full Text]
93. Dahl OE. Mechanisms of hypercoagulability. Thromb Haemost. 1999 Aug;82(2):902-6.[Abstract]
94. Ciglioni M, Targer G, Bergamo Andreis IA, et al. Visceral fat accumulation and its relation to plasma hemostatic factors in healthy men. Arterioscler Thromb Vasc Biol. 1996 Mar;16(3):368-74.[Abstract][Full Text]
95. Luskukoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol. 1998 Jan;18(1):1-6.[Abstract][Full Text]
96. Després J-P, Lemieux I, Bergeron J, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. [Erratum in: Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):e151.)[Abstract][Full Text]
97. Stein PD, Beemath A, Olson RE. Obesity as a risk factor for venous thromboembolism. Am J Med. 2005 Sep;118(9):978-80.[Abstract]
98. Eichinger S, Hron G, Bialonczyk C, et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008 Aug 11;168(15):1678-83.[Abstract]
99. Pomp ER, Rosendaal FR, Doggen CJ. Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use. Am J Hematol. 2008 Feb;83(2):97-102.[Abstract]
100. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009 Aug;7(8):1297-303.[Abstract]
101. Miller GJ, Bauer KA, Cooper JA, et al. Activation of the coagulation pathway in cigarette smokers. Thromb Haemost. 1998 Mar;79(3):549-53.[Abstract]
102. Fultz SL, McGinnis KA, Skanderson M, et al. Association of venous thromboembolism with human immunodeficiency virus and mortality in veterans. Am J Med. 2004 Mar 15;116(6):420-3.[Abstract]
103. World Health Organization. WHO research into global hazards of travel (WRIGHT) project. Final report of phase 1. 2007 [internet publication].[Full Text]
104. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e195S-226S.[Abstract][Full Text]
105. Arya R, Barnes JA, Hossain U, et al. Long-haul flights and the risk of venous thrombosis: a significant risk only when additional risk factors present. Br J Haematol. 2002 Mar;116(3):653-4.[Abstract]
106. Cannagieter SC, Doggen SJM, van Houwelingen HC, et al. Travel-related venous thrombosis: results from a large population-based case control study (MEGA study). PLoS Med. 2006 Aug;3(8):e307.[Abstract][Full Text]
107. Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008 Aug 26;179(5):417-26.[Abstract][Full Text]
108. Besser M, Baglin C, Luddington R, et al. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost. 2008 Oct;6(10):1720-5.[Abstract]
109. Tripodi A, Legnani C, Chantarangkul V, et al. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost. 2008 Aug;6(8):1327-33.[Abstract]
110. Douketis J, Tosetto A, Marcucci M, et al. Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism. Ann Intern Med. 2010 Oct 19;153(8):523-31.[Abstract]
111. American College of Chest Physicians. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST. 2012;141(suppl 2):e1S-801S.[Full Text]
112. Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018 Nov 27;2(22):3198-225.[Abstract][Full Text]
113. Neumann I, Izcovich A, Aguilar R, et al. American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, Sociedad Peruana de Hematología, and SVH 2022 guidelines for prevention of venous thromboembolism in surgical and medical patients and long-distance travelers in Latin America. Blood Adv. 2022 Jun 28;6(12):3636-49.[Abstract][Full Text]
114. Connors JM. Thrombophilia testing and venous thrombosis. N Engl J Med. 2017 Sep 21;377(12):1177-87.[Abstract]
115. Arachchillage DJ, Mackillop L, Chandratheva A, et al. Thrombophilia testing: A British Society for Haematology guideline. Br J Haematol. 2022 Aug;198(3):443-58.[Abstract][Full Text]
116. Stevens SM, Woller SC, Bauer KA, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016 Jan;41(1):154-64.[Abstract][Full Text]
117. Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007;127-35.[Abstract][Full Text]
118. Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism during pregnancy and the puerperium: green-top guideline 37a. April 2015 [internet publication].[Full Text]
119. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007 Aug 15;110(4):1092-7.[Abstract][Full Text]
120. Legnani C, Mattarozzi S, Cini M, et al. Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal. Br J Haematol. 2006 Jul;134(2):227-32.[Abstract]
121. Toh CH, Hoots WK. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007 Mar;5(3):604-6.[Abstract]
122. Andreescu AC, Cushman M, Rosendaal FR. D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study. Thromb Haemost. 2002 Jan;87(1):47-51.[Abstract]
123. Palareti G, Cosmi B, Legnani C, et al. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014 May 30;124(2):196-203.[Abstract][Full Text]
124. Chalmers E, Cooper P, Forman K, et al. Purpura fulminans: recognition, diagnosis and management. Arch Dis Child. 2011 Nov;96(11):1066-71.[Abstract]
125. Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics Consensus Statement on factor V Leiden mutation testing. Genet Med. 2001;3:139-148.[Abstract]
126. Press RD, Bauer KA, Kujovich JL, et al. Clinical utility of factor V Leiden (R506Q) testing for diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med. 2002;126:1304-1318.[Abstract]
127. Abbattista M, Capecchi M, Martinelli I. Treatment of unusual thrombotic manifestations. Blood. 2020 Jan 30;135(5):326-34.[Abstract][Full Text]
128. National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. March 2020 [internet publication].[Full Text]
129. Tseng E, Selby R. Testing for heritable thrombophilia in acute venous thromboembolism. CMAJ. 2017 Jul 4;189(26):E891.[Abstract][Full Text]
130. Marlar RA, Gausman JN. Laboratory testing issues for protein C, protein S, and antithrombin. Int J Lab Hematol. 2014 Jun;36(3):289-95.[Abstract][Full Text]
131. ACOG Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstetrics & Gynecology. 2018 Jul 132(1):p e18-34.
132. NHS (UK). National genomic test directory: testing criteria for rare and inherited disease v4. Oct 2022 [internet publication].[Full Text]
133. Devreese KMJ, de Groot PG, de Laat B, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost. 2020 Nov;18(11):2828-39.[Abstract][Full Text]
134. Richards SJ, Hill A, Hillmen P. Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria. Cytometry B Clin Cytom. 2007 Sep;72(5):291-8.[Abstract][Full Text]
135. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Myeloproliferative Neoplasms [internet publication].[Full Text]
136. Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari Syndrome. Gastroenterology. 2006 Jun;130(7):2031-8.[Abstract]
137. Watson H, Davidson S, Keeling D; Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012 Dec;159(5):528-40.[Abstract][Full Text]
138. Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996 Nov 15;125(10):785-93.[Abstract]
139. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006 Dec 7;355(23):2452-66.[Abstract]
140. Hexner EO. JAK2 V617F: implications for thrombosis in myeloproliferative diseases. Curr Opin Hematol. 2007;14:450-454.[Abstract]
141. Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari Syndrome. Gastroenterology. 2006;130:2031-2038.[Abstract]
142. Press RD, Bauer KA, Kujovich JL, et al. Clinical utility of factor V Leiden (R506Q) testing for diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med. 2002 Nov;126(11):1304-18.[Abstract]
143. Lochhead P, Miedzybrodzka Z. The essential role of genetic counseling in inherited thrombophilia. Semin Hematol. 2007 Apr;44(2):126-9.[Abstract]
144. Vandenbroucke JP, van der Meer FJ, Helmerhorst FM, et al. Factor V Leiden: should we screen oral contraceptive users and pregnant women? BMJ. 1996 Nov 2;313(7065):1127-30.[Abstract][Full Text]
145. Faculty of Sexual & Reproductive Healthcare. FSRH guideline: combined hormonal contraception. November 2020 [internet publication].[Full Text]
146. Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, et al. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing. Blood Adv. 2023 Nov 28;7(22):7101-38.[Abstract][Full Text]
147. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018 Nov 27;2(22):3317-59.[Abstract][Full Text]
148. Devreese KMJ, Ortel TL, Pengo V, et al. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost. 2018 Mar 13;16(4):809-13.[Abstract][Full Text]
149. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(suppl 2):e227S-77S.[Abstract]
150. National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. Aug 2019 [internet publication].[Full Text]
151. Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-944.[Abstract][Full Text]
152. Lyman GH, Carrier M, Ay C, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021 Feb 23;5(4):927-74.[Abstract][Full Text]
153. Farge D, Frere C, Connors JM, et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022 Jul;23(7):e334-47.[Abstract][Full Text]
154. Falanga A, Ay C, Di Nisio M, et al. Venous thromboembolism in cancer patients: ESMO clinical practice guideline. Ann Oncol. 2023 May;34(5):452-67.[Abstract][Full Text]
155. Key NS, Khorana AA, Kuderer NM, et al. Venous Thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023 Jun 1;41(16):3063-71.[Abstract][Full Text]
156. Junqueira DR, Zorzela LM, Perini E. Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev. 2017;(4):CD007557. [Abstract][Full Text]
157. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cancer-associated venous thromboembolic disease [internet publication].[Full Text]
158. Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-9.[Abstract][Full Text]
159. Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019 Feb 21;380(8):720-8.[Abstract][Full Text]
160. Kahale LA, Matar CF, Tsolakian I, et al. Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. 2021 Oct 8;10(10):CD006466.[Abstract][Full Text]
161. Kakkos SK, Caprini JA, Geroulakos G, et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database Syst Rev. 2016 Sep 7;(9):CD005258.[Abstract][Full Text]
162. Dahl OE, Caprini JA, Colwell CW Jr, et al. Fatal vascular outcomes following major orthopedic surgery. Thromb Haemost. 2005 May;93(5):860-6.[Abstract]
163. Cordell-Smith JA, Williams SC, Harper WM, et al. Lower limb arthroplasty complicated by deep venous thrombosis. Prevalence and subjective outcome. J Bone Joint Surg Br. 2004 Jan;86(1):99-101.[Abstract]
164. White RH, Gettner S, Newman JM, et al. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med. 2000 Dec 14;343(24):1758-64.[Abstract][Full Text]
165. Lussana F, Dentali F, Abbate R, et al; Italian Society for Haemostasis and Thrombosis. Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res. 2009 Nov;124(5):e19-25.[Abstract]
166. Becattini C, Pace U, Pirozzi F, et al. Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Blood. 2022 Aug 25;140(8):900-8.[Abstract][Full Text]
167. Guntupalli SR, Brennecke A, Behbakht K, et al. Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm: a randomized clinical trial. JAMA Netw Open. 2020 Jun 1;3(6):e207410.[Abstract][Full Text]
168. Khorana AA, Francis CW, Culakova E, et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007 Mar;5(3):632-4.[Abstract]
169. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996 Jul 1;125(1):1-7.[Abstract]
170. Khan F, Rahman A, Carrier M, et al. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ. 2019 Jul 24;366:l4363.[Abstract][Full Text]
171. Kakkar VV, Howe CT, Flanc C, et al. Natural history of post-operative deep vein thrombosis. Lancet. 1969 Aug 2;2(7614):230-2.[Abstract]
Key Articles
Other Online Resources
Referenced Articles
Sign in to access our clinical decision support tools