title: High risk of pregnancy-related venous thromboembolism in women with multiple thrombophilic defects.
abstract: Pregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. This retrospective family cohort study assessed the risk of venous thromboembolism during pregnancy and puerperium, and the contribution of concomitant thrombophilic defects in families with hereditary antithrombin, protein C or protein S deficiencies. Probands were excluded. Of 222 female relatives, 101 were deficient and 121 non-deficient. Annual incidences of venous thromboembolism were 1.76% in deficient women versus 0.19% in non-deficient women [adjusted relative risk (RR) 11.9; 95% confidence interval (CI), 3.9-36.2]. Other single and multiple thrombophilic defects increased the risk in deficient women from 1.55% to 2.14% and 2.92%, and in non-deficient women from 0.16% to 0.09% and 0.54% respectively. Deficient women were at lower risk (1.37%; 0.80-2.19) than deficient women that had never been pregnant (2.96%; 1.53-5.18); RR 0.5 (0.2-0.99). This difference was due to the predominance of events related to oral contraceptives in deficient women that had never been pregnant (75%), while 71% of events in deficient women that had had at least one pregnancy were pregnancy-related. In conclusion, women with hereditary deficiencies of antithrombin, protein C or protein S are at high risk of pregnancy-related venous thromboembolism. This risk is increased by multiple additional thrombophilic defects.
authors.affiliation: Division of Haemostasis, Thrombosis and Rheology, Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands. n.folkeringa@og.umcg.nl
authors.forename: Nienke
authors.initials: N
authors.lastname: Folkeringa
authors.forename: Jan Leendert P
authors.initials: JL
authors.lastname: Brouwer
authors.forename: Fleurisca J
authors.initials: FJ
authors.lastname: Korteweg
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Jan Jaap H M
authors.initials: JJ
authors.lastname: Erwich
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000293:Adolescent; D000328:Adult; D000991:Antithrombins / Q000172:deficiency; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood*; D020151:Protein C Deficiency / Q000097:blood; D018455:Protein S Deficiency / Q000097:blood; D012189:Retrospective Studies; D012306:Risk; D018570:Risk Assessment; D013923:Thromboembolism / Q000097:blood*; D019851:Thrombophilia / Q000097:blood*; D020246:Venous Thrombosis / Q000097:blood
chemical_list: D000991:Antithrombins