Anesth Analg 2005;101:1886-1887
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000180268.85925.78
LETTER TO THE EDITOR
Major Post-Partum Hemorrhage and Treatment with Recombinant Factor VIIa
Harald Hollnberger,
Elisabeth Gruber, and
Birgit Seelbach-Goebel
Department of Anaesthesia, Barmherzige Brueder Regensburg Hospital, St. Hedwig Clinic, Regensburg, Germany, harald.hollnberger{at}barmherzige-regensburg.de (Hollnberger)
Department of Anaesthesia, Brunico Hospital, Brunico, Italy (Gruber)
Department of Obstetrics and Gynaecology, Barmherzige Brueder Regensburg Hospital, St. Hedwig Clinic, University of Regensburg, Regensburg, Germany (Seelbach-Goebel)
To the Editor:
Major postpartum hemorrhage is a severe complication that accounts for the highest rate of maternal morbidity, with a frequency of 6.7 per 1000 births (1). After all other therapeutic options have been exhausted, emergency hysterectomy often remains the only effective therapy. We administered recombinant factor VIIa (rFVIIa) in three women with major postpartum hemorrhage to avoid hysterectomy.
Case 1: A 31-year-old woman experienced atonia of the uterus after caesarean section and massive bleeding resulting in hemorrhagic shock, metabolic acidosis (pH 6.94; normal range, 7.35–7.45), and impaired coagulation with an International Normalized Ratio (INR) of 1.73 (normal up to 1.3), activated partial thromboplastin time (aPTT) 43 s (normal, 26 to 42 s), and fibrinogen 78 mg/dL (normal range, 150 to 450 mg/dL). Platelet count was 265 x 103/µL (normal range, 130 to 400 x 103/µL) and hemoglobin 4.5 g/dL (normal range, 12 to 16 g/dL). After 7 U of packed red blood cells, 9 U fresh-frozen plasma, and extensive drug therapy, a relaparotomy was performed with intracavitary oxytocin injection into the uterus followed by ligature of both uterine arteries and placement of B-Lynch sutures. Before relaparotomy, 120 µg/kg rFVIIa was given followed by a further dose of 120 µg/kg after 60 min. After the second administration of rFVIIa the coagulation parameters showed considerable improvement and bleeding diminished continuously.
Case 2: A 30-yr-old woman with placenta praevia marginalis delivered spontaneously. She had experienced episodes of vaginal bleeding during pregnancy and birth. There was a delayed detachment of the placenta, circulation instability, and impaired coagulation (INR, 2.26; aPTT, 58 s; fibrinogen, 74 mg/dL, platelet count, 78 x 103/µL, hemoglobin, 3.9 g/dL; pH 7.34). One hour after curettage, intensive vaginal bleeding occurred that could not be stopped by uterine massage, prostaglandin F2 , and a second curettage. Before severe acidosis could develop, two doses of 60 µg/kg rFVIIa were administered within 3 h. The bleeding stopped after the second dose. In total, 10 U packed red blood cells and 13 U fresh-frozen plasma were administered. The patient received 2 U platelet concentrate, as the platelet count was 35 x 103/µL even after the second dose of rFVIIa.
Case 3: A 28-yr-old patient delivered her baby by vacuum extraction and experienced massive vaginal hemorrhage caused by serious laceration of the vagina, necessitating surgical intervention. Oxytocin and prostaglandin F2 were used for therapy of the uterine atonia, to no effect. There were signs of consumptive coagulopathy with an INR of 1.86, aPTT of 77 s, fibrinogen 102 mg/dL, antithrombin 58% (normal range, 80% to 120%), platelets 76 x 103/µL, and hemoglobin 6.5 g/dL. There was mild acidosis with a pH of 7.24. Although 120 µg/kg rFVIIa was administered, slight seeping hemorrhage from the vagina still continued. After a second dose of rFVIIa the blood coagulation variables had almost been completely restored with the exception of a decrease in platelet count (36 x 103/µL). In total, 13 U packed red blood cells, 16 U fresh-frozen plasma, and 2 U platelet concentrates were transfused.
In summary, major postpartum hemorrhage was stopped after two doses of 60–120 µg/kg rFVIIa, and emergency hysterectomy could be avoided. All three patients recovered without residual disorders. The improvement in the coagulation parameters was considerably delayed in patient 1, who had severe acidosis. In vitro, a decrease in pH to 7.0 led to a reduction in the FVIIa activity on phospholipids by 90% and the FVIIa/tissue factor complex was restricted in its effectiveness by more than 60% (2). Binding of rFVIIa to phospholipid structures on the surface of the activated platelets mediates a main mechanism of action causing direct activation of factor X (3). Our experiences indicate that severe acidosis reduces the efficacy of rFVIIa in vivo. Therefore, rFVIIa should be administered before severe acidosis occurs or after correction of the acid-base status. In the case of treatment failures, analyses should include disorders that might have reduced the effect of rFVIIa, such as low fibrinogen levels, thrombocytopenia below 20 x 103/µL, and acidosis.
References
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- Meng ZH, Wolberg AS, Monroe DM, Hoffman M. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J Trauma 2003;55:886–91.[Web of Science][Medline]
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