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Background <p>The ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) is widely used to assess the risk of preeclampsia. However, heparin can transiently increase the level of circulating sFlt-1, making it unclear whether prophylactic subcutaneous unfractionated heparin (UFH)—commonly used for thromboprophylaxis in pregnancy—affects the reliability of this biomarker.</p> Methods <p>We conducted a retrospective cohort study to compare mid-trimester (18w0d-23w6d) sFlt-1 levels and sFlt-1/PlGF ratios in 45 pregnant women receiving prophylactic subcutaneous UFH for antiphospholipid syndrome or a history of thrombosis and 563 controls. We also examined the association between biomarker levels and time elapsed since the last UFH injection.</p> Results <p>Mid-trimester sFlt-1 levels (1900 vs. 1782 pg/mL, <i>p</i> = 0.15) and sFlt-1/PlGF ratios (7.2 vs. 6.7, <i>p</i> = 0.87) were equivalent between the UFH and control groups. Multivariate regression analysis adjusting for maternal age, body mass index, gestational age at sampling, and low-dose aspirin intake confirmed no significant association between prophylactic UFH and sFlt-1 levels or sFlt-1/PlGF ratios. Within the UFH group, no correlation was found between the time since administration (range 63–477&#xa0;min) and sFlt-1 levels (<i>r</i>=-0.049, <i>p</i> = 0.75) or sFlt-1/PlGF ratios (<i>r</i> = 0.019, <i>p</i> = 0.90).</p> Conclusion <p>Prophylactic subcutaneous UFH was not associated with significant differences in sFlt-1/PlGF ratios, and the serum levels were not correlated with the timing of administration within the examined window. These findings suggest that the sFlt-1/PlGF ratio may remain a reliable tool for preeclampsia risk assessment in women receiving UFH prophylaxis under routine clinical sampling conditions.</p>

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Effect of prophylactic subcutaneous unfractionated heparin on the maternal sFlt-1/PlGF ratio: a retrospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月22日

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  • Yuri Yoshida,
  • Takayuki Iriyama,
  • Yu Ariyoshi,
  • Yuji Ida,
  • Eriko Yano,
  • Haruka Matsui,
  • Kensuke Suzuki,
  • Ayako Hashimoto,
  • Mari Ichinose,
  • Masatake Toshimitsu,
  • Seisuke Sayama,
  • Kenbun Sone,
  • Osamu Wada-Hiraike,
  • Keiichi Kumasawa,
  • Miyuki Harada,
  • Yasushi Hirota

摘要

Background

The ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) is widely used to assess the risk of preeclampsia. However, heparin can transiently increase the level of circulating sFlt-1, making it unclear whether prophylactic subcutaneous unfractionated heparin (UFH)—commonly used for thromboprophylaxis in pregnancy—affects the reliability of this biomarker.

Methods

We conducted a retrospective cohort study to compare mid-trimester (18w0d-23w6d) sFlt-1 levels and sFlt-1/PlGF ratios in 45 pregnant women receiving prophylactic subcutaneous UFH for antiphospholipid syndrome or a history of thrombosis and 563 controls. We also examined the association between biomarker levels and time elapsed since the last UFH injection.

Results

Mid-trimester sFlt-1 levels (1900 vs. 1782 pg/mL, p = 0.15) and sFlt-1/PlGF ratios (7.2 vs. 6.7, p = 0.87) were equivalent between the UFH and control groups. Multivariate regression analysis adjusting for maternal age, body mass index, gestational age at sampling, and low-dose aspirin intake confirmed no significant association between prophylactic UFH and sFlt-1 levels or sFlt-1/PlGF ratios. Within the UFH group, no correlation was found between the time since administration (range 63–477 min) and sFlt-1 levels (r=-0.049, p = 0.75) or sFlt-1/PlGF ratios (r = 0.019, p = 0.90).

Conclusion

Prophylactic subcutaneous UFH was not associated with significant differences in sFlt-1/PlGF ratios, and the serum levels were not correlated with the timing of administration within the examined window. These findings suggest that the sFlt-1/PlGF ratio may remain a reliable tool for preeclampsia risk assessment in women receiving UFH prophylaxis under routine clinical sampling conditions.