Hypercoagulability in adolescent girls on oral contraceptives-global coagulation profile and estrogen receptor polymorphisms

Ayesha Zia, Michael U. Callaghan, Joseph H. Callaghan, Anju Sawni, Heather Bartlett, Alcesa Backos, Sharon Marshall, Meera Chitlur, Madhvi Rajpurkar

Research output: Contribution to journalArticle

8 Scopus citations

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 FVIII: 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.

Original languageEnglish (US)
Pages (from-to)725-731
Number of pages7
JournalAmerican Journal of Hematology
Volume90
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Hematology

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    Zia, A., Callaghan, M. U., Callaghan, J. H., Sawni, A., Bartlett, H., Backos, A., Marshall, S., Chitlur, M., & Rajpurkar, M. (2015). Hypercoagulability in adolescent girls on oral contraceptives-global coagulation profile and estrogen receptor polymorphisms. American Journal of Hematology, 90(8), 725-731. https://doi.org/10.1002/ajh.24064