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Preventing Postpartum Hemorrhage (PPH) with Combined Therapy Rather Than Oxytocin Alone Pharmacologic Therapy

  • Amanda J. JONES
    Affiliations
    Johns Hopkins University School of Medicine, Baltimore, MD 21287
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  • Jerome J. FEDERSPIEL
    Affiliations
    Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA
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  • Ahizechukwu C. EKE
    Correspondence
    Corresponding Author: Ahizechukwu C. Eke, MD PhD MPH, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Affiliations
    Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins, University School of Medicine, 600 N Wolfe Street, Phipps 228, Baltimore, MD 21287

    Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287
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      ABSTRACT

      Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70–80% of cases of PPH, thereby remaining the single most common cause. Pharmacotherapy remains the first-line preventative therapy for PPH. These therapies may be single (oxytocin, carbetocin, methylergonovine, ergometrine, misoprostol, prostaglandin analogues, or tranexamic acid), or a combination of these therapies, acting in an additive, infra-additive or synergistic fashion to prevent PPH. Evidence is strong for the use of oxytocin, the first-line uterotonic agent in the United States for prevention of PPH. While carbetocin, a long-acting analogue of oxytocin, is not yet available for use in the United States, it is likely the most effective single pharmacologic therapy for prevention of PPH and need for additional uterotonics. Use of second-line uterotonics such as methylergonovine, misoprostol, and carboprost in combination with oxytocin, has an additive or synergistic effect and a greater risk reduction for PPH prevention compared to oxytocin alone, and therefore combined therapy rather than oxytocin alone should be advised for preventing PPH. Tranexamic acid has been found to be both effective and safe for decreasing maternal mortality in women with PPH, and prophylactic use of tranexamic acid may decrease the need for packed red blood cell transfusions and/or uterotonics. The WOMAN-2 Trial, designed to assess if tranexamic acid prevents PPH in women with moderate to severe anemia undergoing vaginal delivery, is currently recruiting participants. The additive, infra-additive or synergistic action of oxytocin in combination with other second-line therapies deserves further study.

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