title: Hypercoagulability in adolescent girls on oral contraceptives-global coagulation profile and estrogen receptor polymorphisms.
abstract: Oral contraceptive (OCP) induced changes on coagulation are complex with high inter-individual variability. The precise reason for differences in this variability is unknown. We hypothesized that global coagulation assays better delineate these changes and variability in hypercoagulability may be the result of differences in estrogen metabolism and thrombophilia. Fifty-two adolescents initiating OCPs were prospectively enrolled; 33 subjects completed the study. Samples were analyzed prior to and after OCPs for procoagulant and anticoagulant factor activities and thrombin generation (TG) +/-thrombomodulin. Participants were genotyped for common thrombophilia and estrogen receptor-α (ESR-α) single nucleotide polymorphisms (SNPs). SNP genotypes were compared to coagulation parameters; TG parameters and differences pre and post OCPs were examined. At baseline, a striking finding was elevated FVIII levels. FVL was absent in all and F2 G20210A was present in one participant. The ESR-α polymorphism was present in heterozygous state in 59% and homozygous state in 21% participants. There were no differences in VWF levels and
  C after being on OCPs. Protein S levels decreased with OCPs. Sixty percent of participants showed evidence of hypercoagulability on TG testing on OCPs. Higher thrombin peak and endogenous thrombin potential (ETP) were seen on TG after OCPs. With thrombomodulin, ETP and thrombin peak did not decrease after OCPs, signifying 'thrombomodulin resistance'. We demonstrated that OCPs induce a state of "variable" hypercoagulability in adolescents, predominantly through the protein S pathway. Genetic and nongenetic factors may account for the variable increase in hypercoagulability. Further research is needed to understand this.
authors.affiliation: Department of Pediatrics, Division of Hematology Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Zia
authors.affiliation: Division of Hematology/Oncology, the Carman Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Michael U
authors.initials: MU
authors.lastname: Callaghan
authors.affiliation: Department of Accounting and Finance, School of Business Administration, Oakland University, Rochester, Michigan.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Callaghan
authors.affiliation: Department of Pediatrics, Michigan State University of Human Medicine, Flint, Michigan.
authors.forename: Anju
authors.initials: A
authors.lastname: Sawni
authors.affiliation: Division of Adolescent Medicine, Department of Pediatrics, The Carman Ann Adams, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Heather
authors.initials: H
authors.lastname: Bartlett
authors.affiliation: Division of Adolescent Medicine, Department of Pediatrics, The Carman Ann Adams, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Alcesa
authors.initials: A
authors.lastname: Backos
authors.affiliation: Division of Adolescent Medicine, Department of Pediatrics, The Carman Ann Adams, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Sharon
authors.initials: S
authors.lastname: Marshall
authors.affiliation: Division of Hematology/Oncology, the Carman Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Meera
authors.initials: M
authors.lastname: Chitlur
authors.affiliation: Division of Hematology/Oncology, the Carman Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Madhvi
authors.initials: M
authors.lastname: Rajpurkar
mesh_terms: D000293:Adolescent; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D003276:Contraceptives, Oral / Q000009:adverse effects*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005165:Factor V / Q000235:genetics / Q000378:metabolism; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009644:Norgestrel / Q000009:adverse effects / Q000031:analogs & derivatives*; D020641:Polymorphism, Single Nucleotide; D017293:Protein S / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D018180:Thrombomodulin / Q000097:blood; D019851:Thrombophilia / Q000097:blood* / Q000139:chemically induced / Q000235:genetics; D055815:Young Adult; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D003276:Contraceptives, Oral; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D017293:Protein S; D018180:Thrombomodulin; C095381:factor V Leiden; D014841:von Willebrand Factor; D009644:Norgestrel; D004997:Ethinyl Estradiol; D005165:Factor V; D005169:Factor VIII; C017576:norgestimate; D013917:Thrombin