Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Journal of Thrombosis and Thrombolysis
Published in: Journal of Thrombosis and Thrombolysis 1/2016

Open Access 01-01-2016

Guidance for the evaluation and treatment of hereditary and acquired thrombophilia

Authors: Scott M. Stevens, Scott C. Woller, Kenneth A. Bauer, Raj Kasthuri, Mary Cushman, Michael Streiff, Wendy Lim, James D. Douketis

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2016

Login to get access

Abstract

Thrombophilias are hereditary and/or acquired conditions that predispose patients to thrombosis. Testing for thrombophilia is commonly performed in patients with venous thrombosis and their relatives; however such testing usually does not provide information that impacts management and may result in harm. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for thrombophilia testing in five clinical situations: following 1) provoked venous thromboembolism, 2) unprovoked venous thromboembolism; 3) in relatives of patients with thrombosis, 4) in female relatives of patients with thrombosis considering estrogen use; and 5) in female relatives of patients with thrombosis who are considering pregnancy. Additionally, guidance is provided regarding the timing of thrombophilia testing. The role of thrombophilia testing in arterial thrombosis and for evaluation of recurrent pregnancy loss is not addressed. Statements are based on existing guidelines and consensus expert opinion where guidelines are lacking. We recommend that thrombophilia testing not be performed in most situations. When performed, it should be used in a highly selective manner, and only in circumstances where the information obtained will influence a decision important to the patient, and outweigh the potential risks of testing. Testing should not be performed during acute thrombosis or during the initial (3-month) period of anticoagulation.
Literature
1.
Egeberg O (1965) Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 13:516–530PubMed
2.
3.
Comp PC, Esmon CT (1984) Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 311:1525–1528PubMedCrossRef
4.
Dahlback B, Hildebrand B (1994) Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci USA 91:1396–1400PubMedPubMedCentralCrossRef
5.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) 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 88:3698–3703PubMed
6.
Fechtel K, Osterbur ML, Kehrer-Sawatzki H, Stenson PD, Cooper DN (2011) Delineating the hemostaseome as an aid to individualize the analysis of the hereditary basis of thrombotic and bleeding disorders. Hum Genet 130:149–166PubMedPubMedCentralCrossRef
7.
8.
Rodger MA, Kahn SR, Wells PS et al (2008) Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 179:417–426PubMedPubMedCentralCrossRef
9.
Lutsey PL, Cushman M, Heckbert SR, Tang W, Folsom AR (2011) Longer legs are associated with greater risk of incident venous thromboembolism independent of total body height. The Longitudinal Study of Thromboembolism Etiology (LITE). Thromb Haemost 106:1–184CrossRef
10.
Baudouy D, Moceri P, Chiche O et al (2015) B blood group: a strong risk factor for venous thromboembolism recurrence. Thromb Res 136:107–111PubMedCrossRef
11.
12.
Kearon C, Akl E (2014) Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 123:1794–1801PubMedCrossRef
13.
14.
Stegnar M (2010) Thrombophilia screening–at the right time, for the right patient, with a good reason. Clin Chem Lab Med 48(Suppl 1):S105–S113PubMed
15.
Nicolaides A, Hull RD, Fareed J (2013) Thrombophilia. Clin App Thromb Hemost 19:177–187
16.
Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR (2005) Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 293:2352–2361PubMedCrossRef
17.
Dalen JE (2008) Should patients with venous thromboembolism be screened for thrombophilia? Am J Med 121:458–463PubMedCrossRef
18.
Gohil R, Peck G, Sharma P (2009) The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls. Thromb Haemost 102:360–370PubMed
19.
Wu O, Robertson L, Twaddle S et al (2006) Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (Treats) Study. Health Technol Assess 10:1–110PubMedCrossRef
20.
21.
Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing. National Clinical Guideline Centre (UK). London: Royal College of Physicians 2012
22.
Baglin T, Luddington R, Brown K, Baglin C (2003) Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 362:523–526PubMedCrossRef
23.
Simone B, De Stefano V, Leoncini E et al (2013) Risk of venous thromboembolism associated with single and combined effects of factor V Leiden, prothrombin 20210A and methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol 28:621–647PubMedPubMedCentralCrossRef
24.
American College of Obstetricians Gynecologists Women’s Health Care Physicians (2013) ACOG Practice Bulletin No. 138: inherited thrombophilias in pregnancy. Obstet Gynecol 122:706–717CrossRef
25.
Baglin T, Gray E, Greaves M et al (2010) Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 149:209–220PubMedCrossRef
26.
Jennings I, Kitchen S, Woods TA, Preston FE (2005) Multilaboratory testing in thrombophilia through the United Kingdom National External Quality Assessment Scheme (Blood Coagulation) Quality Assurance Program. Semin Thromb Hemost 31:66–72PubMedCrossRef
27.
Segal JB, Brotman DJ, Necochea AJ et al (2009) Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 301:2472–2485PubMedCrossRef
28.
Hellmann EA, Leslie ND, Moll S (2003) Knowledge and educational needs of individuals with the factor V Leiden mutation. J Thromb Haemost 1:2335–2339PubMedCrossRef
29.
Cohn DM, Vansenne F, Kaptein AA, De Borgie CA, Middeldorp S (2008) The psychological impact of testing for thrombophilia: a systematic review. J Thromb Haemost 6:1099–1104PubMedCrossRef
30.
Bank I, Scavenius MP, Buller HR, Middeldorp S (2004) Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice. Thromb Res 113:7–12PubMedCrossRef
31.
32.
Mahmoodi BK, Brouwer JL, Ten Kate MK et al (2010) A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. J Thromb Haemost 8:1193–1200PubMedCrossRef
33.
Reitter-Pfoertner S, Waldhoer T, Mayerhofer M et al (2013) The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism. Thromb Haemost 109:79–84PubMedCrossRef
34.
Rabinovich A, Cohen JM, Prandoni P, Kahn SR (2014) Association between thrombophilia and the post-thrombotic syndrome: a systematic review and meta-analysis. J Thromb Haemost 12:14–23PubMedCrossRef
35.
Coppens M, Reijnders JH, Middeldorp S, Doggen CJ, Rosendaal FR (2008) Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost 6:1474–1477PubMedCrossRef
36.
Hicks LK, Bering H, Carson KR et al (2013) The ASH Choosing Wisely(R)campaign: five hematologic tests and treatments to question. Hematology 2013:9–14PubMedCrossRef
37.
38.
Pernod G, Biron-Andreani C, Morange PE et al (2009) Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline. J Mal Vasc 34:156–203PubMedCrossRef
39.
Evaluation of Genomic Applications in Practice and Prevention Working Group (2011) Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G > A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Gen Med 13:67–76
40.
Boutitie F, Pinede L, Schulman S et al (2011) Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ 342:d3036PubMedPubMedCentralCrossRef
41.
Eichinger S, Minar E, Hirschl M et al (1999) The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene. Thromb Haemost 81:14–17PubMed
42.
Eichinger S, Weltermann A, Mannhalter C et al (2002) The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med 162:2357–2360PubMedCrossRef
43.
Couturaud F, Leroyer C, Tromeur C et al (2014) Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood 124:2124–2130PubMedPubMedCentralCrossRef
44.
Tosetto A, Iorio A, Marcucci M et al (2012) Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 10:1019–1025PubMedCrossRef
45.
Eichinger S, Heinze G, Jandeck LM, Kyrle PA (2010) Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 121:1630–1636PubMedCrossRef
46.
Kearon C, Spencer FA, O’Keeffe D et al (2015) d-Dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Ann Intern Med 162:27–34PubMedCrossRef
47.
Donadini MP, Ageno W, Antonucci E et al (2014) Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis. A patient-level meta-analysis. Thromb Haemost 111:172–179PubMedCrossRef
48.
Baldwin M, Moore H, Rudarakanchana N, Gohel M, Davies A (2013) Post-thrombotic syndrome: a clinical review. J Thromb Haemost 11:795–805PubMedCrossRef
49.
Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA, Group AFVLW (2001) American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Gen Med 3:139–148CrossRef
50.
51.
52.
Lijfering WM, Brouwer JL, Veeger NJ et al (2009) Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 113:5314–5322PubMedCrossRef
53.
Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ (2009) The value of family history as a risk indicator for venous thrombosis. Arch Intern Med 169:610–615PubMedCrossRef
54.
Zoller B, Ohlsson H, Sundquist J, Sundquist K (2013) Familial risk of venous thromboembolism in first-, second- and third-degree relatives: a nationwide family study in Sweden. Thromb Haemost 109:458–463PubMedCrossRef
55.
Sorensen HT, Riis AH, Diaz LJ, Andersen EW, Baron JA, Andersen PK (2011) Familial risk of venous thromboembolism: a nationwide cohort study. J Thromb Haemost 9:320–324PubMedCrossRef
56.
Wu O, Robertson L, Twaddle S et al (2005) Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol 131:80–90PubMedCrossRef
57.
Creinin MD, Lisman R, Strickler RC (1999) Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril 72:646–651PubMedCrossRef
58.
59.
Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333PubMedCrossRef
60.
Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY (2008) Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ 336:1227–1231PubMedPubMedCentralCrossRef
61.
James AH, Jamison MG, Brancazio LR, Myers ER (2006) Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 194:1311–1315PubMedCrossRef
62.
Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos A-M, Vandvik PO (2012) VTE, thrombophilia, antithrombotic therapy, and pregnancy. Chest 141:e691S–e736SPubMedPubMedCentral
63.
Lussana F, Dentali F, Abbate R et al (2009) Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 124:e19–e25PubMedCrossRef
64.
Pabinger I, Grafenhofer H, Kaider A et al (2005) Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost 3:949–954PubMedCrossRef
65.
Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd (2005) Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 143:697–706PubMedCrossRef
66.
Villani M, Tiscia GL, Margaglione M et al (2012) Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias. J Thromb Haemost 10:223–228PubMedCrossRef
67.
Rodger MA, Hague WM, Kingdom J et al (2014) Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 384:1673–1683PubMedCrossRef
68.
Bain E, Wilson A, Tooher R, Gates S, Davis LJ, Middleton P (2014) Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Rev 2:CD001689PubMed
69.
Duhl AJ, Paidas MJ, Ural SH et al (2007) Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 197(457):e1–e21PubMed
70.
Lockwood C, Wendel G, Committee on Practice Bulletins Obstetrics (2011) Practice bulletin no. 124: inherited thrombophilias in pregnancy. Obstet Gynecol 118:730–740PubMedCrossRef
71.
McLintock C, Brighton T, Chunilal S et al (2012) Recommendations for the prevention of pregnancy-associated venous thromboembolism. Aust N Z J Obstet Gynaecol 52:3–13PubMedCrossRef
72.
Adcock DM, Gosselin R (2015) Direct oral anticoagulants (DOACs) in the laboratory: 2015 review. Thromb Res 136:7–12PubMedCrossRef
73.
Pintao MC, Ribeiro DD, Bezemer ID et al (2013) Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study. Blood 122:3210–3219PubMedCrossRef
74.
Cushman M (2014) Thrombophilia testing in women with venous thrombosis: the 4 P’s approach. Clin Chem 60:134–137PubMedCrossRef
75.
Lindhoff-Last E, Luxembourg B (2008) Evidence-based indications for thrombophilia screening. Vasa 37:19–30PubMedCrossRef
76.
Cohen W, Castelli C, Suchon P et al (2014) Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model. J Thromb Haemost 12:138–146CrossRef
77.
Davis SM, Branch DW (2010) Thromboprophylaxis in pregnancy: who and how? Obstet Gynecol Clin North Am 37:333–343PubMedCrossRef
78.
Culwell KR, Curtis KM, del Carmen Cravioto M (2009) Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review. Obstet Gynecol 114:341–353PubMedCrossRef
79.
Wu O, Robertson L, Langhorne P et al (2005) Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The thrombosis: risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost 94:17–25PubMed
Metadata
Title
Guidance for the evaluation and treatment of hereditary and acquired thrombophilia
Authors
Scott M. Stevens
Scott C. Woller
Kenneth A. Bauer
Raj Kasthuri
Mary Cushman
Michael Streiff
Wendy Lim
James D. Douketis
Publication date
01-01-2016
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 1/2016
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-015-1316-1

Other articles of this Issue 1/2016

Journal of Thrombosis and Thrombolysis 1/2016 Go to the issue

OriginalPaper

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism

OriginalPaper

Pharmacology of anticoagulants used in the treatment of venous thromboembolism

OriginalPaper

Guidance for the prevention and treatment of cancer-associated venous thromboembolism

OriginalPaper

The epidemiology of venous thromboembolism

OriginalPaper

Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment

EditorialNotes

Management of venous thromboembolism: clinical guidance from the Anticoagulation Forum
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits