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Pi Is 0002937817302934
Pi Is 0002937817302934
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OBSTETRICS
Topical application of recombinant activated factor VII
during cesarean delivery for placenta previa
Birgit T. B. G. Schjoldager, MD, DMSc; Emmeli Mikkelsen, MB; Malene R. Lykke, MD; Jørgen Præst, MD;
Anne-Mette Hvas, MD, PhD; Lars Heslet, MD, DMSc; Niels J. Secher, MD; Jannie D. Salvig, MD, PhD;
Niels Uldbjerg, MD, DMSc
BACKGROUND: During cesarean delivery in patients with placenta factor VII:clot, and thrombin generation in peripheral blood prior to and
previa, hemorrhaging after removal of the placenta is often challenging. In 15 minutes after removal of the placenta. We also tested these blood
this condition, the extraordinarily high concentration of tissue factor at the coagulation variables in 5 women with cesarean delivery planned for other
placenta site may constitute a principle of treatment as it activates reasons. Mann-Whitney test was used for unpaired data.
coagulation very effectively. The presumption, however, is that tissue RESULTS: In all 5 cases, the uterotomy was closed under practically dry
factor is bound to activated factor VII. conditions and the median blood loss was 490 (range 300-800) mL. There
OBJECTIVE: We hypothesized that topical application of recombinant were no adverse effects of recombinant activated factor VII and we did not
activated factor VII at the placenta site reduces bleeding without affecting measure factor VII to enter the circulation. Neither did we observe changes
intravascular coagulation. in thrombin generation, fibrinogen, activated partial thrombin time,
STUDY DESIGN: We included 5 cases with planned cesarean delivery international normalized ratio, and platelet count in the peripheral circu-
for placenta previa. After removal of the placenta, the surgeon applied a lation (all P values >.20).
swab soaked in recombinant activated factor VII containing saline (1 mg in CONCLUSION: This study indicates that in patients with placenta
246 mL) to the placenta site for 2 minutes; this treatment was repeated previa, topical recombinant activated factor VII may diminish bleeding from
once if the bleeding did not decrease sufficiently. We documented the the placenta site without initiation of systemic coagulation.
treatment on video recordings and measured blood loss. Furthermore, we
determined hemoglobin concentration, platelet count, international Key words: factor VIIa, hemostatic agents, maternal mortality, placenta
normalized ratio, activated partial thrombin time, fibrinogen (functional), previa, postpartum hemorrhage, topical treatment
Introduction orrhage (PPH) including manipulation Topical treatment of the placental site
After both vaginal and cesarean delivery, of the uterus and administration of with rFVIIa has not been studied yet.
blood flow through the placental site uterotonics are insufficient to stop the Tissue factor (TF) is a receptor for both
decreases from 5-6 L/min to 0 within a bleeding. Further treatment may involve inert factor VII (FVII) and activated
few minutes.1 This happens due to: (1) balloon tamponade or rolled gauze FVII (FVIIa) and thus TF constitutes the
the immense contraction of the myo- packing of the uterus as well as surgical key trigger of the blood coagulation
metrium of the uterus, which com- interventions with compression sutures cascade. TF is constitutively expressed by
presses the spiral arteries; and (2) a local or pelvic artery embolization.1,3 cells surrounding blood vessels where it
activation of the coagulation system. Additionally, hemostatic agents for is considered to shape a “hemostatic
During cesarean delivery for placenta both systemic and topical use have been envelope.”14-16 In addition, the TF con-
previa (PP), which occurs in 0.4% of all introduced to enhance coagulation at the centration in the amniotic fluid exceeds
pregnancies,2 the risk of hemorrhage is placenta site. The systemic treatment, that in all other body fluids17,18 and TF is
high as the contractile capacity of the however, with recombinant activated abundant in the placenta and in the
thin myometrium of the lower uterine factor VII (rFVIIa)4,5 and perhaps also uterine wall, ie, in the epithelial and the
segment is limited. Therefore, standard with tranexamic acid6 increases the risk decidual cells thereby providing the
procedures used for postpartum hem- of thromboembolic events that are pregnant uterus with an extra hemo-
worsened by the hypercoagulative effects static potential.14-21
of pregnancy.1,7 Therefore, topical TF reacts as a cofactor in augmenting
Cite this article as: Schjoldager BTBG, Mikkelsen E,
treatments are attractive. They span the activity of FVIIa 1000-fold.7,16
Lykke MR, et al. Topical application of recombinant
activated factor VII during cesarean delivery for placenta from collagen, gelatin, polysaccharides, Indeed, TF plays a critical role in uter-
previa. Am J Obstet Gynecol 2017;216:608.e1-5. chelating agents, and Monsel solution to ine hemostasis: in mice, TF expressed by
carriers with coagulative active agents the uterine epithelium, decidua, and
0002-9378
ª 2017 The Author(s). Published by Elsevier Inc. This is an such as thrombin and fibrinogen. Some trophoblast is reported to prevent fatal
open access article under the CC BY-NC-ND license (http:// of the topical treatments are based on hemorrhage immediately after the
creativecommons.org/licenses/by-nc-nd/4.0/). nonhuman tissue and blood-derived detachment of the placenta from the
http://dx.doi.org/10.1016/j.ajog.2017.02.024
agents, which heighten the risk of uterine wall.19
immunological reactions and infections In human placental sections, immu-
in the uterus.8-13 nostaining for TF indicates that
FIGURE 3
Topical recombinant activated factor VII and placenta previa (PP)
Thrombin generation: PP cases and controls prior to and after cesarean delivery. Time until initial thrombin generation (lag time), P > .99; maximum
concentration of thrombin generation (peak), P ¼ .84; time to peak of thrombin generation (ttpeak), P > .99; endogenous thrombin potential (ETP),
P ¼ .31. P values indicate whether there is significant difference between changes in laboratory variables in 2 groups.
Schjoldager et al. Topical rFVIIa and placenta previa. Am J Obstet Gynecol 2017.