title: Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor.
abstract: BACKGROUND
  Low molecular weight heparin (LMWH) has been shown to be effective in decreasing the recurrence of placenta-mediated complications of pregnant women. The aim of this study was to determine the effect of LMWH on circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PLGF) in pregnant women who required anticoagulation therapy.
  
  
  METHODS
  A longitudinal prospective cohort study was performed including pregnant women in whom anticoagulation therapy by LMWH during pregnancy was clinically indicated (n = 33). Healthy pregnant women, matched for gestational age, who did not require thromboprophylaxis served as controls (n = 29). Maternal plasma samples were obtained throughout gestation every 4 weeks and stored at -70 °C. Maternal plasma concentrations of sFlt-1, sEng and PLGF were determined by ELISA and compared between the two groups.
  
  
  RESULTS
  Patients treated with LMWH had significantly increased circulatory levels of PLGF during the third trimester compared with controls (28-34 weeks: 719.2 pg/ml vs 558.6 pg/ml at, p < 0.01; 35-40 weeks: 975.6 pg/ml vs 511.2 pg/ml, p < 0.01, respectively). In contrast, circulatory levels of sFlt-1 and sEng were similar between the LMWH treatment group and controls throughout gestation. Consistent with these findings, the ratio of sFlt-1/PLGF was lower in patients treated with LMWH compared to controls (28-34 weeks: 1.9 vs 7.2, p < 0.05; 35-40 weeks: 5 vs 12.9, p < 0.05, respectively).
  
  
  CONCLUSIONS
  Anticoagulation treatment of pregnant women with LMWH is associated with a pro-angiogenic state. These findings may explain the effectiveness of LMWH in the prevention of placenta-mediated complications of pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel. Electronic address: yoav.yinon27@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Yinon
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Ben Meir
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Margolis
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Lipitz
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Schiff
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: M J
authors.initials: MJ
authors.lastname: Simchen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D010922:Placenta Diseases / Q000097:blood* / Q000517:prevention & control*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000188:drug therapy; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000188:drug therapy*; D011257:Pregnancy Proteins / Q000097:blood*; D015854:Up-Regulation
chemical_list: D006495:Heparin, Low-Molecular-Weight; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor
keywords: Angiogenic factors; Low molecular weight heparin; PLGF; sEng; sFlt-1