|LETTER TO THE EDITOR
|Year : 2015 | Volume
| Issue : 1 | Page : 37-38
Use of low-dose recombinant factor VIIa in a pregnant patient with factor VII deficiency undergoing a minor surgery
Hüseyin Ulas Pinar, Betül Basaran, Rafi Dogan
Department of Anesthesiology, Baskent University, Ankara, Turkey
|Date of Web Publication||15-Apr-2015|
Dr. Hüseyin Ulas Pinar
Mavisehir Mah, 2040 Sok. Albatross Sitesi A7, Blok No: 156 Karsiyaka, Izmir
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Pinar HU, Basaran B, Dogan R. Use of low-dose recombinant factor VIIa in a pregnant patient with factor VII deficiency undergoing a minor surgery. J Obstet Anaesth Crit Care 2015;5:37-8
|How to cite this URL:|
Pinar HU, Basaran B, Dogan R. Use of low-dose recombinant factor VIIa in a pregnant patient with factor VII deficiency undergoing a minor surgery. J Obstet Anaesth Crit Care [serial online] 2015 [cited 2019 Dec 6];5:37-8. Available from: http://www.joacc.com/text.asp?2015/5/1/37/155200
Factor VII, a Vitamin K-dependent coagulation factor with a glycoprotein structure synthesized in the liver is a zymogen with a serine protease structure, which is converted to factor VIIa, its active form, by proteolysis. Its half-life is 2-5 h, the shortest among all coagulation factors. Factor VII initiates the extrinsic coagulation pathway by binding to the tissue factor. Factor VII deficiency is a rare bleeding disorder which has an autosomal recessive inheritance pattern and a frequency of 1/500,000.  Most patients with factor VII deficiency are diagnosed by an isolated prolongation of prothrombin time (PT). Patients with a factor VII level below 10% may present with epistaxis, menorrhagia, postoperative and postpartum hemorrhages as well as bleeding episodes related to the oral cavity.  Whether asymptomatic patients should be prophylactically treated before a surgical procedure is controversial.  Factor VII replacement is conventionally done by administering fresh frozen plasma, prothrombin complex concentrate, and plasma-derived factor VII concentrates. 
Recombinant factor VIIa concentrate has been increasingly used in recent years. However, prophylactic and therapeutic dose requirements or dose before a surgical intervention remain controversial. Recombinant activated factor VIIa was developed to treat spontaneous and/or surgery-related hemorrhages in patients with hemophilia A and B who develop alloantibodies against factor VIII and FIX after replacement therapy.  The recommended dose for such patients has been determined as 90 μg/kg before and during surgery. The recommended dose for patients with factor VII deficiency, on the other hand, ranges from 15 to 30 μg/kg every 4-6 h until hemostasis achieved; prophylactic dose, however, has not been determined yet.  In the present report, we aimed to present a case of 9 weeks pregnant woman with factor VII deficiency, who was given low-dose recombinant factor VIIa before dilatation and curettage. We also aimed to discuss the therapy in the light of the previous literature.
A 38-year-old, 9-week pregnant, 107 kg woman who had congenital factor VII deficiency diagnosed presented to the hospital for dilatation and curettage because of elective termination under general anesthesia she had no additional health problem. Her history was remarkable for previous factor VII treatments profilactically each administered separately in three previous pregnancies. She gave no history of spontaneous bleeding. Physical examination was also normal.
Complete blood count and biochemistry results were normal. PT was 31.7 s, international normalized ratio (INR) was 2.58, and activated thromboplastin time was 30.3 s. Thus, factor VII level was measured and found below 1%. Two hours prior dilatation and curettage procedure she was administered intravenous bolus of recombinant FVIIa concentrate (NovoSeven RT; Novo Nordisk, Bagsvaerd, Denmark) at a dose of 9.3 μg/kg (1 mg total dose) in 3 min. The blood sample was taken instantly, and PT level was 9.4 s and INR was 0.64. Anesthesia induction was achieved with midazolam 2 mg, fentanyl 100 μg, and propofol 200 mg. Anesthesia maintenance was achieved with sevoflurane 1.5-2% in 60-40% N 2 O-O 2 and mask ventilation. No bleeding complication was observed during the procedure, and the patient was awakened and sent to the inpatient ward. She developed no bleeding complication during follow-up. A second dose same as the first one of recombinant FVIIa concentrate was readministered 4 h after the first dose. PT level was measured 13.8 s, INR was 1.1, and PTZ was 30.1 s in the second blood sample drawn 2 h after the second dose. The patient was free of bleeding complication in the next 24 h and she was discharged. Postoperative 1 st -3 rd -7 th day follow-ups were also free of bleeding, as evidenced by telephone interview with the patient.
Factor VII deficiency, the most common of the rare bleeding disorders, has a particular importance for public health in our country where consanguineous marriage is common because the disorder exhibits an autosomal recessive inheritance pattern. Majority of patients with this rare bleeding disorder are asymptomatic and diagnosed incidentally. It is not entirely clear how bleeding risk should be determined and which treatment strategies should be applied.  Recombinant activated factor VIIa dose and duration have not been clearly determined although it is commonly used.  Literature data indicate a wide range of doses and administration frequencies. Mariani et al. reported a mean total dose of 7.2-510 μg/kg in a 38-patient study on minor surgeries or invasive procedures, of which majority were dental extractions. In that series, factor VIIa was used at a dose of 10-20 μg/kg for endoscopic biopsies and of 15-60 μg/kg for minor surgical procedures. The authors recommended a median total dose of 20 μg/kg for minor surgical procedures in patients without a bleeding history.  We also administered a prophylactic dose of 9.3 μg/kg (total 1 mg) followed by the second dose same as the first one 4 h later despite absence of bleeding. We did not consider maintenance therapy upon verification that no bleeding occurred, as Mariani et al. did.
Some of the previous studies used lower doses for surgical procedures. For example, Livnat et al. performed thyroidectomy, total knee prosthesis surgery, and inguinal hernia repair with a single dose of 3-6 μg/kg of recombinant factor VIIa in 3 patients with factor VII levels between 1% and 5%.  Case reports from Turkey, on the other hand, have generally reported higher doses. Göktaş et al. administered 5 doses of factor VIIa, one being at preoperative period, at a dosage of 90 μg/kg in a patient undergoing varicocele operation.  Canatan et al. administered nine doses of factor VIIa concentrates at a dosage of 20 μg/kg in a 4-year-old pediatric patient with a factor level of 4% who underwent circumcision. 
Use of recombinant factor VIIa is recommended in patients with factor VII deficiency scheduled to undergo a surgical operation although detailed trials are clearly needed in addition to case reports to reach a consensus concerning dosage and frequency of administration. Considering the high cost of the medication, especially for the anesthesiologists it is important to avoid unnecessary high-dose applications in developing countries.
| References|| |
Brummel-Ziedins K, Mann KG. Molecular basis of blood coagulation. In: Hoffman R, Benz EJ, Shattil SJ, editors. Hematology Basic Principles and Practice. 2 nd
ed. New York: Churchill Livingstone; 1995. p. 1566-87.
Perry DJ. Factor VII deficiency. Blood Coagul Fibrinolysis 2003;14 Suppl 1:47-54.
Livnat T, Shenkman B, Spectre G, Tamarin I, Dardik R, Israeli A, et al.
Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery. Blood Coagul Fibrinolysis 2012;23:379-87.
Bauer KA. Treatment of factor VII deficiency with recombinant factor VIIa. Haemostasis 1996;26 Suppl 1:155-8.
Lusher JM, Roberts HR, Davignon G, Joist JH, Smith H, Shapiro A, et al
. A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group. Haemophilia 1998;4:790-8.
Brenner B, Wiis J. Experience with recombinant-activated factor VII in 30 patients with congenital factor VII deficiency. Hematology 2007;12:55-62.
Mariani G, Dolce A, Napolitano M, Ingerslev J, Giansily-Blaizot M, Di Minno MD, et al.
Invasive procedures and minor surgery in factor VII deficiency. Haemophilia 2012;18:e63-5.
Goktas U, Kati I, Tekin M, et al
. Factor VII Deficiency and Anesthesia Turk Rean Der Dergisi 2008;36:258-60.
Canatan D, Eren E, Ozgüner IF, Duman H, Eren C, Büyükyavuz I, et al.
The use of recombinant activated factor VII in the circumcision operation in the case of a congenital factor VII deficiency. Blood Coagul Fibrinolysis 2007;18:375-6.