{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:48:50Z","timestamp":1757702930347},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"844","license":[{"start":{"date-parts":[[1996,2,1]],"date-time":"1996-02-01T00:00:00Z","timestamp":823132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although there are numerous risk factors for venous thromboembolic disease, the term \u2018thrombophilia\u2019 refers only to those familial or acquired disorders of the haemostatic system that result in an increased risk of thrombosis. The inherited thrombophilias include antithrombin III deficiency, resistance to activated protein C (factor V Leiden), protein C and protein S deficiencies as well as some rare forms of dysfibrinogenaemia. It is possible that other inherited conditions might also predispose to thrombosis. In contrast, when using the above definition, the antiphospholipid syndrome is the only genuine acquired thrombophilic state. Patients who have thromboembolic disease at a young age with no provoking event or who have a positive family history or whose thrombosis involves an unusual site should be investigated for thrombophilia. The management of a patient identified as having a laboratory abnormality associated with thrombophilia will depend on a variety of factors such as the patient\u2019s individual and family thrombotic history, the site of the thrombosis and the presence of other prothrombotic risk factors. The use of prophylactic anticoagulation during pregnancy and the puerperium requires particularly careful consideration in thrombophilic women. As more becomes known about the thrombophilias it will become possible to formulate more exact guidelines as to the management of these conditions.<\/jats:p>","DOI":"10.1136\/pgmj.72.844.87","type":"journal-article","created":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T21:49:00Z","timestamp":1230587340000},"page":"87-94","source":"Crossref","is-referenced-by-count":11,"title":["Guidelines for the management of thrombophilia. Department of Haematology, The Royal London Hospital, Whitechapel, London, UK"],"prefix":"10.1093","volume":"72","author":[{"given":"J D","family":"Cavenagh","sequence":"first","affiliation":[{"name":"Department of Haematology, The Royal London Hospital , Whitechapel, London E1 1BB , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B T","family":"Colvin","sequence":"additional","affiliation":[{"name":"Department of Haematology, The Royal London Hospital , Whitechapel, London E1 1BB , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1996,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1001\/archinte.1991.00400050081016","article-title":"A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism","volume":"151","author":"Anderson, F.A.; Brownell Wheeler, H.","year":"1991","unstructured":"Anderson FA, Brownell Wheeler H, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1991; 151: 933-8.","journal-title":"Arch Intern Med"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1136\/jcp.43.9.703","article-title":"Standards in Haematology. Guidelines on the investigation and management of thrombophilia","volume":"43","author":"British Committee for","year":"1990","unstructured":"British Committee for Standards in Haematology. Guidelines on the investigation and management of thrombophilia. J Clin Pathol 1990; 43: 703-9.","journal-title":"J Clin Pathol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1365-2141.1994.tb04902.x","article-title":"The molecular genetics of antithrombin deficiency","volume":"87","author":"Olds, R.J.; Lane, D.A.; Thein, S.L.","year":"1994","unstructured":"Olds RJ, Lane DA, Thein SL. The molecular genetics of antithrombin deficiency. Br J Haematol 1994; 87: 221-6.","journal-title":"Br J Haematol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0308-2261(21)00229-0","article-title":"Antithrombin III deficiency and thromboembolism","volume":"10","author":"Thaler, E.; Lechner, K.","year":"1981","unstructured":"Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10: 369-90.","journal-title":"Clin Haematol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1182\/blood.V78.9.2299.2299","article-title":"a2-Macroglobulin may provide protection from thromboembolic events in antithrombin IIIdeficient children","volume":"78","author":"Mitchell, L.; Piovella, F.; Ofosu, F.; Andrew, M.","year":"1991","unstructured":"Mitchell L, Piovella F, Ofosu F, Andrew M. a2-Macroglobulin may provide protection from thromboembolic events in antithrombin IIIdeficient children. Blood 1991; 78: 2299-304.","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1055\/s-0038-1645218","article-title":"Thrombosis and pregnancy in congenital deficiencies of AT III, protein C or protein S: study of 78 women","volume":"63","author":"Conard, J.; Horellou, M.H.; Van Dreden, P.; Lecompte, T.; Samama, M.","year":"1990","unstructured":"Conard J, Horellou MH, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies of AT III, protein C or protein S: study of 78 women. Thromb Haemost 1990; 63: 319-24.","journal-title":"Thromb Haemost"},{"key":"ref_7","first-page":"1004","article-title":"Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: prediction of a cofactor to","volume-title":"activated protein C. Proc Nati Acad Sci USA","volume":"90","author":"Dahlback, B.; Carlsson, M.; Svensson, P.J.","year":"1993","unstructured":"Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Nati Acad Sci USA 1993; 90: 1004-8."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(94)92939-4","article-title":"Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V","volume":"343","author":"Voorberg, J.; Roelse, J.; Koopman, R.","year":"1994","unstructured":"Voorberg J, Roelse J, Koopman R, et al. Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V. Lancet 1994; 343: 1535-8.","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/369064a0","article-title":"Mutation in blood coagulation factor V associated with resistance to activated protein C","volume":"369","author":"Bertina, R.M.; Koeleman, B.P.C.; Koster, T.","year":"1994","unstructured":"Bertina RM, Koeleman BPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1056\/NEJM199402243300801","article-title":"Resistance to activated protein C as a basis for venous thrombosis","volume":"330","author":"Svensson, P.J.; Dahlback, B.","year":"1994","unstructured":"Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. 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Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991-6.","journal-title":"N Engl J Med"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/blood.V65.1.15.15","article-title":"Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood","volume":"65","author":"Marcianack, E.; Wilson, H.D.; Marlar, R.A.","year":"1985","unstructured":"Marcianack E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood 1985; 65: 15-20.","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1056\/NEJM199111283252207","article-title":"Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate","volume":"325","author":"Dreyfus, M.; Magny, J.F.; Bridey, F.","year":"1991","unstructured":"Dreyfus M, Magny JF, Bridey F, et al. 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N Engi J Med 1995; 332: 993-7.","journal-title":"N Engi J Med"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1056\/NEJM199106273242606","article-title":"Oral anticoagulant drugs","volume":"324","author":"Hirsh, J.","year":"1991","unstructured":"Hirsh J. Oral anticoagulant drugs. N EnglJ Med 1991; 324: 1865-75.","journal-title":"N EnglJ Med"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1056\/NEJM199105303242206","volume":"324","author":"Heparin, Hirsh J.","year":"1991","unstructured":"Hirsh J. Heparin. N Engl Med 1991; 324: 1565-74.","journal-title":"N Engl Med"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1136\/jcp.46.6.489","article-title":"Standards in Haematology. Guidelines on the prevention, investigation and management of thrombosis associated with pregnancy","volume":"46","author":"British Committee for","year":"1993","unstructured":"British Committee for Standards in Haematology. Guidelines on the prevention, investigation and management of thrombosis associated with pregnancy. J Clin Pathol 1993; 46: 489-96.","journal-title":"J Clin Pathol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1055\/s-0038-1642752","article-title":"Management of pregnancy in women with antithrombin III congenital defect: report of four cases","volume":"59","author":"V, De Stefano; G, Leone; S, De Carolis","year":"1988","unstructured":"De Stefano V, Leone G, De Carolis S, et al. Management of pregnancy in women with antithrombin III congenital defect: report of four cases. Thromb Haemost 1988; 59: 193-6.","journal-title":"Thromb Haemost"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1365-2141.1994.tb04878.x","article-title":"Prevalence of antithrombin deficiency in the healthy population","volume":"87","author":"Tait, R.C.; Walker, I.D.; Perry, D.J.","year":"1994","unstructured":"Tait RC, Walker ID, Perry DJ, et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87: 106-12.","journal-title":"Br J Haematol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1111\/j.1365-2141.1994.tb06757.x","article-title":"Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy?","volume":"87","author":"Cook, G.; Walker, I.D.; McCall, F.; Conkie, J.A.; Greer, I.A.","year":"1994","unstructured":"Cook G, Walker ID, McCall F, Conkie JA, Greer IA. Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy? Br J Haematol 1994; 87: 873-5.","journal-title":"Br J Haematol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1055\/s-0038-1642480","article-title":"the GTH study group on natural inhibitors. Thrombotic risk of women with hereditary antithrombin III-, protein C-and protein S-deficiency taking oral contraceptive medication","volume":"71","author":"Pabinger, I, Schneider B and","year":"1994","unstructured":"Pabinger I, Schneider B and the GTH study group on natural inhibitors. Thrombotic risk of women with hereditary antithrombin III-, protein C-and protein S-deficiency taking oral contraceptive medication. Thromb Haemost 1994; 71: 548-52.","journal-title":"Thromb Haemost"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2141.1994.tb04999.x","article-title":"Further evidence that activated protein C resistance can be misdiagnosed as inherited functional protein S deficiency","volume":"88","author":"Cooper, P.C.; Hampton, K.K.; Makris, M.; Abuzenadah, A.; Paul, B.; Preston, F.E.","year":"1994","unstructured":"Cooper PC, Hampton KK, Makris M, Abuzenadah A, Paul B, Preston FE. 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