title: Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals.
abstract: The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Ming Y
authors.initials: MY
authors.lastname: Lim
authors.affiliation: Lineberger Comprehensive Cancer Center Biostatistics Core, Chapel Hill, NC, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Deal
authors.affiliation: Hematology/Oncology, St. Jude Heritage Medical Group, Fullerton, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Kim
authors.affiliation: Center for Applied Genomics & Precision Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Musty
authors.affiliation: Haemostasis-Thrombosis Unit, Hotel-Dieu University Hospital, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Conard
authors.affiliation: Department of Medicine - DIMED, University of Padua Medical School, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.affiliation: Haemostasis Unit, University Hospital of Dijon, Dijon, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dutrillaux
authors.affiliation: Princess Iman Research and Laboratory Sciences Center, King Hussein Medical Center, Amman, Jordan.
authors.forename: Suhair S
authors.initials: SS
authors.lastname: Eid
authors.affiliation: Academic Medical Center, Department of Vascular Medicine, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Institute of Laboratory Medicine, Municipal Hospital Hietzing-Rosenhuegel, Vienna, Austria.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Halbmayer
authors.affiliation: Haemostasis Laboratory, Rangueil Hospital, Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Boneu
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Moia
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. smoll@med.unc.edu.
authors.forename: Stephan
authors.initials: S
authors.lastname: Moll
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002648:Child; D005165:Factor V / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011516:Prothrombin / Q000235:genetics*; D012306:Risk; D019851:Thrombophilia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin
keywords: factor V Leiden; prothrombin; thrombophilia; thrombosis; venous thromboembolism