Author Information
Saxena A*, Pardeshi S**, Gupta AS***.
(* Junior Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, India.)
Abstract
Out of many coagulation disorders, factor X deficiency is one of the rarest disorders. Positive pregnancy outcomes in these patients have been rarely reported. Here we are presenting a case report of such a patient who throughout her pregnancy meticulously followed up with hematology and obstetrics department of our hospital.
Introduction
Factor X deficiency is a rare disorder, with autosomal recessive mode of inheritance. It has an incidence of 1 in 1,000,000.[1] It presents with excessive bleeding if levels of factor X fall below 10%. Homozygus individuals can have severe bleeding episodes whereas heterozygus individuals, though usually asymptomatic, can also present with varying degrees of bleeding. Women with factor X deficiency (FXD) who want to become pregnant face uncertain risks to themselves and to an unborn infant from hemorrhagic complications during pregnancy and parturition. This is a case report of our patient, a 27 years old, primigravida, married since 2.5 years who was referred to our OPD at 11 weeks of gestation with a rare coagulation disorder of factor X deficiency.
Case Report
A primigravida, 27 years old, at 11 weeks of gestation was referred to our ANC OPD for further management of her pregnancy. At 11 years of age she had attained her menarche. Due to complaints of menorrhagia not responding to medical management, she was investigated for coagulation disorders and was diagnosed with Factor X deficiency. Since then she had been taking combined oral contraceptive pills (OCP’s) to avoid menses. Intermittently when she tried to stop OCP’s she had heavy bleeding during menses and hence she took them everyday thereafter. She was also advised to get her husband evaluated for any bleeding disorder so as to plan pregnancy in future. Accordingly her husband was evaluated and there was no evidence of any hematological disorder. She stopped consuming the pills when she wanted to conceive.
We referred her to hematology department, where she was counseled regarding the high risk related to pregnancy, increased risk of spontaneous abortions, need for monitoring of any bleeding episode and increased risk of morbidity and mortality related to bleeding.
She had regular follow ups with the hematologist and the obstetrician. At 24 weeks of gestation she had an episode of hematuria for which she came to our emergency services department. No active intervention was required and bleeding resolved on its own. Near term, she was advised to arrange for approximately 70 units of fresh frozen plasma (FFPs).
At the onset of labor, she came to our receiving room with term gestation. She was admitted. Hemoglobin on admission was 11.9 gm %. Availability of 70 FFPs were confirmed. Vital parameters were monitored. When she entered the active phase of labor, as per hematologist advice 7 units of FFPs (at the rate of 15 ml/kg) were transfused. At the onset of second stage of labor 4 more units of FFPs were transfused. Due to non-descent of the fetal head for an hour in the second stage of labor, an emergency lower segment cesarean section was performed. A healthy male baby was born. Neonatologist’s evaluated the neonate and found no evidence of any bleeding in the neonate. Neonatal evaluation for bleeding disorders was deferred for 6 months. Total blood loss was estimated to be 700 ml. Post-operative hemoglobin was 9.6 gm%. As per hematologist advice 4 more FFP’s were transfused after 12 hours of delivery. Vital parameters remained stable throughout the post-operative period. No abnormal bleeding was noted. No postpartum hemorrhage occurred. As per hematologist advice she was again transfused 4 units of FFP’s on day 3 and another 4 on day 6. Her factor 10 levels done on day 3 were >25%. She was discharged on day 7. She was advised double barrier method for contraception and later on resumption of hormonal contraception.
Discussion
FXD is one of the rare disorders of coagulation. Factor X gets converted into factor Xa in the final cascade of coagulation pathway.[2] FXD can be divided into two types, Type 1, a quantitative defect and Type 2, a qualitative defect with near normal antigen levels but reduced FX activity.
As FXD, is extremely rare, not many successful pregnancies have been reported in literature. Complications like miscarriage, abruptio placentae, premature labor, fetal death and bleeding episodes in the baby are commonly encountered.
Fertility rate among women with FXD is unknown. Most women with factor X deficiency are encountered with complains like menorrhagia, prolonged menses, hemorrhagic ovarian cyst, post coital bleeding. In case of severe FXD, prolonged menorrhagia and post coital bleeding reduce the frequency of coitus thus hindering their fertility.[3]
Vijakupar reported that five of the eight women with severe FXD had refractory menorrhagia making conception difficult. One patient required hysterectomy, the other two couldn’t be weaned off OCPs, one did conceive but had an abortion and one was declared infertile.[4]
Mamopoulos et al has described pregnancy in a 34 year old patient with FXD.[1] At 40 weeks, she was admitted with false labor and was transfused FFPs with a loading dose of 20 ml/kg of body weight. The same dose was repeated after 4 days when she spontaneously went into labor. She underwent an emergency LSCS due to a non reassuring cardiotocogram. A healthy baby delivered and no bleeding problems were encountered during the operation. Two more units of FFP were administered to maintain FX levels above 20%.
Another case report published in 1994, describes the outcomes of 4 pregnancies in a patient with factor X deficiency.[5] In her first 2 pregnancies she was transfused FFPs at the time of delivery in view of acute bleeding episodes. She delivered at 21 and 25 weeks of gestation respectively and babies died in their neonatal period due to severe prematurity. In the next 2 pregnancies she was transfused earlier in pregnancy and the outcome of both these pregnancies was good, one being at 34 weeks and the second at 32 weeks.
Romagnolo et al reported a pregnancy in a 30 year old, nulliparus, homozygus patient, where an elective cesarean section was planned.[6] Prior to cesarean section, she was given an intravenous concentration of Vitamin K dependent factors, one hour prior to surgery to prevent post partum hemorrhage. She was given the complex for another 4 days after her delivery, but her prothrombin time value fell to 7% of the normal, the next day. Teixeira published a case report about a 33 year old nulliparus patient.[7] An ultrasound done at approximately 8 weeks of gestation showed detachment of the smooth chorion. It regressed completely with bed rest and 1000 IU of prothrombin complex concentrate. An elective cesarean section was done at 38 weeks. Prophylaxis of bleeding using prothrombin complex concentrate was given pre-operatively and for three consecutive days postpartum.The post operative period was uneventful. FXD is an autosomal recessive disorder and follows Mendelian inheritance patterns. Majority cases of FXD are caused by missense mutations, duplications and partial deletions.[8] In pregnancy, there is a modest physiological rise of factor X. Also there is an increase in FVIII, VWF and fibrinogen levels and overall there is a prothrombotic state in normal pregnancy. Circulating FX levels rise in pregnant states to roughly 1.3 times the non-pregnant values and return to baseline post delivery.[9,10] For women with very low baseline levels of FX activity, this rise may be only a few points or none at all. The risk for preterm labor appears to be 2.5 times higher in FXD women.[11] Amongst 9 of the 24 pregnancies reporting preterm deliveries, four died and three were extremely premature. In advanced countries, due to easy availability of factor X concentrates, prophylaxis as well as treatment of any peripartum bleeding can be effectively managed, whereas in developing countries due to difficulty in getting factor X, FFP is used for the same.
Conclusion
Though little is known about the pregnancy outcomes in factor X deficient states due to the rarity of the disorder itself, however with early antenatal registration at tertiary care centers, regular follow ups, early anticipation of complications and prophylactic measures, a good pregnancy outcome can be expected in these patients.
References
Saxena A, Pardeshi S, Gupta AS. Successful Pregnancy In a Factor X Deficient Woman. JPGO 2019. Volume 6 No.1. Available from: https://www.jpgo.org/2019/01/successful-pregnancy-in-factor-x.html
Saxena A*, Pardeshi S**, Gupta AS***.
(* Junior Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, India.)
Abstract
Out of many coagulation disorders, factor X deficiency is one of the rarest disorders. Positive pregnancy outcomes in these patients have been rarely reported. Here we are presenting a case report of such a patient who throughout her pregnancy meticulously followed up with hematology and obstetrics department of our hospital.
Introduction
Factor X deficiency is a rare disorder, with autosomal recessive mode of inheritance. It has an incidence of 1 in 1,000,000.[1] It presents with excessive bleeding if levels of factor X fall below 10%. Homozygus individuals can have severe bleeding episodes whereas heterozygus individuals, though usually asymptomatic, can also present with varying degrees of bleeding. Women with factor X deficiency (FXD) who want to become pregnant face uncertain risks to themselves and to an unborn infant from hemorrhagic complications during pregnancy and parturition. This is a case report of our patient, a 27 years old, primigravida, married since 2.5 years who was referred to our OPD at 11 weeks of gestation with a rare coagulation disorder of factor X deficiency.
Case Report
A primigravida, 27 years old, at 11 weeks of gestation was referred to our ANC OPD for further management of her pregnancy. At 11 years of age she had attained her menarche. Due to complaints of menorrhagia not responding to medical management, she was investigated for coagulation disorders and was diagnosed with Factor X deficiency. Since then she had been taking combined oral contraceptive pills (OCP’s) to avoid menses. Intermittently when she tried to stop OCP’s she had heavy bleeding during menses and hence she took them everyday thereafter. She was also advised to get her husband evaluated for any bleeding disorder so as to plan pregnancy in future. Accordingly her husband was evaluated and there was no evidence of any hematological disorder. She stopped consuming the pills when she wanted to conceive.
We referred her to hematology department, where she was counseled regarding the high risk related to pregnancy, increased risk of spontaneous abortions, need for monitoring of any bleeding episode and increased risk of morbidity and mortality related to bleeding.
She had regular follow ups with the hematologist and the obstetrician. At 24 weeks of gestation she had an episode of hematuria for which she came to our emergency services department. No active intervention was required and bleeding resolved on its own. Near term, she was advised to arrange for approximately 70 units of fresh frozen plasma (FFPs).
At the onset of labor, she came to our receiving room with term gestation. She was admitted. Hemoglobin on admission was 11.9 gm %. Availability of 70 FFPs were confirmed. Vital parameters were monitored. When she entered the active phase of labor, as per hematologist advice 7 units of FFPs (at the rate of 15 ml/kg) were transfused. At the onset of second stage of labor 4 more units of FFPs were transfused. Due to non-descent of the fetal head for an hour in the second stage of labor, an emergency lower segment cesarean section was performed. A healthy male baby was born. Neonatologist’s evaluated the neonate and found no evidence of any bleeding in the neonate. Neonatal evaluation for bleeding disorders was deferred for 6 months. Total blood loss was estimated to be 700 ml. Post-operative hemoglobin was 9.6 gm%. As per hematologist advice 4 more FFP’s were transfused after 12 hours of delivery. Vital parameters remained stable throughout the post-operative period. No abnormal bleeding was noted. No postpartum hemorrhage occurred. As per hematologist advice she was again transfused 4 units of FFP’s on day 3 and another 4 on day 6. Her factor 10 levels done on day 3 were >25%. She was discharged on day 7. She was advised double barrier method for contraception and later on resumption of hormonal contraception.
Discussion
FXD is one of the rare disorders of coagulation. Factor X gets converted into factor Xa in the final cascade of coagulation pathway.[2] FXD can be divided into two types, Type 1, a quantitative defect and Type 2, a qualitative defect with near normal antigen levels but reduced FX activity.
As FXD, is extremely rare, not many successful pregnancies have been reported in literature. Complications like miscarriage, abruptio placentae, premature labor, fetal death and bleeding episodes in the baby are commonly encountered.
Fertility rate among women with FXD is unknown. Most women with factor X deficiency are encountered with complains like menorrhagia, prolonged menses, hemorrhagic ovarian cyst, post coital bleeding. In case of severe FXD, prolonged menorrhagia and post coital bleeding reduce the frequency of coitus thus hindering their fertility.[3]
Vijakupar reported that five of the eight women with severe FXD had refractory menorrhagia making conception difficult. One patient required hysterectomy, the other two couldn’t be weaned off OCPs, one did conceive but had an abortion and one was declared infertile.[4]
Mamopoulos et al has described pregnancy in a 34 year old patient with FXD.[1] At 40 weeks, she was admitted with false labor and was transfused FFPs with a loading dose of 20 ml/kg of body weight. The same dose was repeated after 4 days when she spontaneously went into labor. She underwent an emergency LSCS due to a non reassuring cardiotocogram. A healthy baby delivered and no bleeding problems were encountered during the operation. Two more units of FFP were administered to maintain FX levels above 20%.
Another case report published in 1994, describes the outcomes of 4 pregnancies in a patient with factor X deficiency.[5] In her first 2 pregnancies she was transfused FFPs at the time of delivery in view of acute bleeding episodes. She delivered at 21 and 25 weeks of gestation respectively and babies died in their neonatal period due to severe prematurity. In the next 2 pregnancies she was transfused earlier in pregnancy and the outcome of both these pregnancies was good, one being at 34 weeks and the second at 32 weeks.
Romagnolo et al reported a pregnancy in a 30 year old, nulliparus, homozygus patient, where an elective cesarean section was planned.[6] Prior to cesarean section, she was given an intravenous concentration of Vitamin K dependent factors, one hour prior to surgery to prevent post partum hemorrhage. She was given the complex for another 4 days after her delivery, but her prothrombin time value fell to 7% of the normal, the next day. Teixeira published a case report about a 33 year old nulliparus patient.[7] An ultrasound done at approximately 8 weeks of gestation showed detachment of the smooth chorion. It regressed completely with bed rest and 1000 IU of prothrombin complex concentrate. An elective cesarean section was done at 38 weeks. Prophylaxis of bleeding using prothrombin complex concentrate was given pre-operatively and for three consecutive days postpartum.The post operative period was uneventful. FXD is an autosomal recessive disorder and follows Mendelian inheritance patterns. Majority cases of FXD are caused by missense mutations, duplications and partial deletions.[8] In pregnancy, there is a modest physiological rise of factor X. Also there is an increase in FVIII, VWF and fibrinogen levels and overall there is a prothrombotic state in normal pregnancy. Circulating FX levels rise in pregnant states to roughly 1.3 times the non-pregnant values and return to baseline post delivery.[9,10] For women with very low baseline levels of FX activity, this rise may be only a few points or none at all. The risk for preterm labor appears to be 2.5 times higher in FXD women.[11] Amongst 9 of the 24 pregnancies reporting preterm deliveries, four died and three were extremely premature. In advanced countries, due to easy availability of factor X concentrates, prophylaxis as well as treatment of any peripartum bleeding can be effectively managed, whereas in developing countries due to difficulty in getting factor X, FFP is used for the same.
Conclusion
Though little is known about the pregnancy outcomes in factor X deficient states due to the rarity of the disorder itself, however with early antenatal registration at tertiary care centers, regular follow ups, early anticipation of complications and prophylactic measures, a good pregnancy outcome can be expected in these patients.
References
- Mamopoulos A, Vakalopoulou S, Lefkou E, Fileli A, Garipidou V, Mavromatidis G et al. Pregnancy in a patient with severe factor X deficiency. Haemophilia. 2009;15(6):1351-1353.
- Menegatti M, Peyvandi F. Factor X Deficiency. Seminars in Thrombosis and Hemostasis. 2009;35(04):407-415.
- Nance D, Josephson NC, Paulyson-Nunez K, James AH. Factor X deficiency and pregnancy: preconception counselling and therapeutic options. Haemophilia. 2012;18(3):e277-e285.
- Vijapurkar M, Mota L, Shetty S, Ghosh K. Menorrhagia and reproductive health in rare bleeding disorders: a study from the Indian subcontinent. Haemophilia. 2009;15(1):199-202.
- Kumar M, Mehta P. Congenital coagulopathies and pregnancy: Report of four pregnancies in a factor X-deficient woman. American Journal of Hematology. 1994;46(3):241-244.
- Romagnolo C, Burati S, Ciafonni S, Fattori E, Franchi M, Zanon E et al. Severe factor X deficiency in pregnancy: case report and review of literature. Hemophilia. 2004;10(5):665-8
- Teixeira PS, Oliveira PS, Guerra JCC, Hamerschlak N, Colombini MP, Kalil R. Factor X deficiency and pregnancy: case report and counselling. Haemophilia. 2012;18(1):e11-e12.
- Uprichard J, Perry DJ. Factor X deficiency. Blood Reviews. 2002;16(2):97-110.
- Condie RG. A Serial Study Of Coagulation Factors XII, XI And X In Plasma In Normal Pregnancy And In Pregnancy Complicated By Pre-Eclampsia. BJOG: An International Journal of Obstetrics and Gynaecology. 1976;83(8):636-639.
- Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thrombosis and Haemostasis. 2010;103(04):718-727.
- Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ.Births: Final Data for 2015. Natl Vital Stat Rep. 2017;66(1):1.
Saxena A, Pardeshi S, Gupta AS. Successful Pregnancy In a Factor X Deficient Woman. JPGO 2019. Volume 6 No.1. Available from: https://www.jpgo.org/2019/01/successful-pregnancy-in-factor-x.html