|Year : 2021 | Volume
| Issue : 1 | Page : 68-70
Anticoagulation in pregnant women with mechanical heart valve prostheses: Case reports and a literature review
Philip Alaba Adebola1, Folasade A Daniel1, Yusuf A Oshodi2, Abidoye Gbadegesin2, Olagoke K Ale3, Ayodeji O Oluwole4, Olabode Falase5, Mobolaji A Oludara5, Jonathan Nwiloh6
1 Department of Medicine, LASUTH/LASUCOM, Ikeja, Nigeria
2 Department of Obstetrics and Gynaecology, LASUTH/LASUCOM, Ikeja, Nigeria
3 Department of Medicine, LUTH/CMUL, Idi-Araba, Lagos, Nigeria
4 Department of Obstetrics and Gynaecology, LUTH/CMUL, Idi-Araba, Lagos, Nigeria
5 Surgery, LASUTH/LASUCOM, Ikeja, Nigeria
6 Department of Surgery, St. Joseph Hospital, Atlanta, Georgia
|Date of Submission||24-Oct-2020|
|Date of Decision||27-Dec-2020|
|Date of Acceptance||09-Jan-2021|
|Date of Web Publication||25-Feb-2021|
Dr. Philip Alaba Adebola
Department of Medicine, Division of Cardiology, LASUTH/LASUCOM, Ikeja, Lagos
Source of Support: None, Conflict of Interest: None
The choice and regimen of anticoagulation therapy in pregnant women with mechanical valve prostheses have always been a daunting task. It is a delicate balance that takes into consideration the risk of thromboembolic complications in the mother and the risk of potential Warfarin embryopathy to the foetus. Medical practice in a low socioeconomic setting also has the peculiar challenge of financial constraints on the part of the patients and difficulties in monitoring the efficacy of anticoagulation therapy. We report our experience in managing two pregnant women with mechanical valve prostheses and review the existing literature on this complex but interesting subject.
Keywords: Anticoagulation therapy, Lagos State University Teaching Hospital, maternal and foetal outcomes, mechanical heart valves, pregnancy
|How to cite this article:|
Adebola PA, Daniel FA, Oshodi YA, Gbadegesin A, Ale OK, Oluwole AO, Falase O, Oludara MA, Nwiloh J. Anticoagulation in pregnant women with mechanical heart valve prostheses: Case reports and a literature review. Niger Postgrad Med J 2021;28:68-70
|How to cite this URL:|
Adebola PA, Daniel FA, Oshodi YA, Gbadegesin A, Ale OK, Oluwole AO, Falase O, Oludara MA, Nwiloh J. Anticoagulation in pregnant women with mechanical heart valve prostheses: Case reports and a literature review. Niger Postgrad Med J [serial online] 2021 [cited 2021 Jul 30];28:68-70. Available from: https://www.npmj.org/text.asp?2021/28/1/68/310164
| Introduction|| |
Anticoagulation therapy in pregnant women with mechanical valve prostheses has always been a subject of intensive debate, in view of the known teratogenicity associated with the preferred oral Vitamin K antagonist., This teratogenicity is particularly pronounced during the period of embryogenesis, in the first trimester of pregnancy. The effects of warfarin embryopathy in the first trimester include midfacial hypoplasia and stippled epiphyses. Warfarin foetopathy, due to exposure to warfarin therapy in the second and third trimester, can also manifest with central nervous system and eye complications (hydrocephalus and optic atrophy).,, In addition, warfarin use can result to miscarriages up to 20-week gestation or stillbirth after 20-week gestation., Unfortunately, the efficacy of the injectable heparin anticoagulation therapies cannot be completely guaranteed. This is in addition to the much higher cost and inconvenience to the patient, of multiple daily heparin injections, compared to daily single dose oral Vitamin K antagonist. We present two case reports of our experience with managing this challenging clinical scenario in a low socioeconomic setting.
| Case Reports|| |
Patient number 1
T. A. is a 39-year-old female who was diagnosed with severe rheumatic heart disease with severe mitral valve stenosis/mitral valve regurgitation (MS/MR) in 2001. The patient had a mechanical mitral valve prosthesis (ST JUDES VALVE) replacement of the native mitral valve on the 20th May, 2005 at Lagos State University Teaching Hospital (LASUTH), Ikeja. Thereafter, the patient was commenced on therapeutic anticoagulation therapy with tablet warfarin with a prothrombin time, international normalised ratio (PT/INR) target range of 2.5–3.5. She was subsequently discharged to our cardiology clinic for follow-up. The patient and her fiancée had extensive preconception counselling session with the cardiologist (lead author), just before they got married in late 2008. The possible risks associated with anticoagulation therapy during pregnancy were fully explained to the intended couple.
The patient reported to the cardiology clinic in late 2011, with about an 8-week history of amenorrhoea. Before this time, the patient claimed to have had at least three first trimester miscarriages between 2010 and early 2011. She was unaware that she was pregnant before these incidents. Because of her previous unpleasant experiences, she decided to stop the warfarin anticoagulation therapy as soon as she suspected that she was pregnant. The pregnancy was confirmed, and the patient was immediately booked for regular antenatal clinic (ANC). The long-term plan for managing her cardiac status in pregnancy was discussed with her obstetrician. The plan was to recommence her on low-dose tablet warfarin 5 mg nocte, since previous PT/INR suggested that she was within the therapeutic target of 2.5–3.5 at that dose. This also took into consideration the fact that the patient was unwilling to switch over to heparin injections, mainly because of financial constraints. The patient compliance to the warfarin therapy and PT/INR monitoring was erratic, partly because of her fear of the possible effect of warfarin on the foetus. The patient was admitted at 36-week Gestation Age (GA) for elective caesarean section (C/S) at the Lagos University Teaching Hospital , Idi-Araba and was commenced on subcutaneous unfractionated (UF) heparin 5000 IU 8 hourly up to 12 h before the elective C/S. The patient had elective C/S delivery of a healthy baby boy on the 4th May, 2012, about 2 weeks after admission. After a period of tablets warfarin treat ment overlap with subcutaneous UF. Heparin therapy, the heparin was discontinued. She was maintained on tablet warfarin 5 mg nocte, approximately 2 weeks after delivery.
The patient achieved a second successful pregnancy in early 2016 and presented to the cardiology clinic after 6 weeks of amenorrhoea. Again, she had discontinued her warfarin therapy as soon as she suspected that she was pregnant. She was immediately booked for ANC, and long-term management plan for her cardiac condition in pregnancy was discussed with the obstetrician. Her anticoagulation treatment course was similar to that of the previous pregnancy, with obvious poor drug compliance. The patient was admitted at 33-week GA following complaints of recurrent abdominal discomfort and malaise. She was commenced on subcutaneous UF heparin 5000 IU 8 hourly. Patients had elective C/S delivery of a baby boy at GA 37 weeks. After few days, period of initial tablet warfarin treatment overlaps with subcutaneous UF. In heparin therapy, the heparin was discontinued. She was maintained on tablet warfarin 5 mg nocte, approximately 2 weeks after delivery. Her baby had neonatal jaundice which resolved within 4 weeks post-delivery.
Patient number 2
T. O. is a 38-year-old female who was diagnosed with moderately severe mixed rheumatic valve disease severe MS/MR and moderate aortic valve stenosis and regurgitation, at the end of 2nd trimester of her first pregnancy, following symptoms of heart failure. She was managed with anti-heart failure medications. She had an elective CS delivery of a baby boy at 36-week GA, on the 26th June, 2015. She was subsequently referred for double valve replacement surgery and strongly advised to avoid further pregnancy, in view of her deteriorating cardiac status. The patient underwent a double valve replacement of the native mitral and aortic valves with mechanical ONIX Valve prostheses at the National Cardio-thoracic Centre, UNTH, Enugu, on the 8th May, 2018. The patient was commenced on tablet warfarin with regular PT/INR therapeutic monitoring and was subsequently discharged on the16th May, 2018.
The patient reported to our cardiology clinic on March 2019, with a 5-week history of amenorrhea and a positive pregnancy test. The patient could not afford the recommended optimal dose of subcutaneous low-molecular weight (LMW) heparin 80 mg 12 hourly initially, due to financial constraints. Her tablet warfarin dose was reduced from 8 mg nocte that she was previously on prior to the pregnancy, to a safer, guideline-recommended dose of 5 mg nocte, with regular PT/INR monitoring. Due to the inadequate low PT/INR target achieved, the patient was counselled and eventually switched to subcutaneous LMW heparin 80 mg 12 hourly. The patient was able to source the LMW heparin injections directly from the manufacturer at a fairly subsidized price. The warfarin was discontinued by the 9th week of gestation.
The patient was admitted at 36-week GA and scheduled for elective C/S at LASUTH, Ikeja. She was maintained on subcutaneous LMW heparin 80 mg 12 hourly, up to 12 h before the elective C/S. The patient subsequently had elective C/S delivery of healthy TWIN baby boys at 37-week GA. She was recommenced on subcutaneous LMW heparin 80 mg 12 hourly, a day after delivery. After few days, period of initial tablet warfarin treatment overlaps with subcutaneous LMW. In heparin therapy, the heparin was discontinued. The patient was fully reconverted back to oral anticoagulation therapy approximately 3 weeks post-delivery. Her twin babies are doing fine with no observed anomaly so far.
| Discussion|| |
Despite the challenges of inadequate anticoagulation therapy monitoring, poor drug compliance and financial constraints on the part of the two patients, they were able to give birth to healthy babies. Patient number 1 was particularly poorly compliant to her low-dose oral Vitamin K antagonist. This attitude was probably informed by her previous experience of repeated first trimester spontaneous abortions with warfarin therapy. Unfortunately, she could not afford regular heparin injections due to severe financial constraints. Patient number 2 was relatively more economically buoyant and could afford LMW heparin injection virtually throughout the pregnancy. We insisted on heparin for the management of patient number 2 because we were not able to achieve therapeutic INR target with guideline-recommended daily oral warfarin dose of 5 mg or less. Earlier observations had suggested that pregnant women, who were on daily dose of tablet warfarin of 5 mg or less, were more likely to give birth to healthy babies, compared to those on more than 5 mg/day of oral warfarin.,, However, oral warfarin is not completely safe at any time, throughout the duration of pregnancy., The dose and choice of injectable heparin have also been controversial.,,
Three modes of anticoagulation therapy regimen in pregnant women with mechanical valve prostheses have been suggested., Each has its own advantages and disadvantages. First, oral Vitamin K antagonist given throughout the period of pregnancy up till 36-week GA. Second, sequential therapy regimen in which heparin injections are given in the first trimester up till 12 weeks of gestation, and subsequently, oral Vitamin K antagonist given for the remaining period of pregnancy up till 36-week GA. Lastly, heparin injections, either UF. Heparin or LMW. Heparin, given throughout the period of pregnancy. There is a general consensus that all pregnant women with mechanical heart valves should be admitted as from 34 to 36-week GA and commenced on heparin injections till at least 12 h before delivery., Previous observations suggest that giving warfarin throughout the period of pregnancy is associated with the lowest risk of maternal mortality and thromboembolic complications., Unfortunately, it also has the highest risk of embryopathy and lowest live birth rate. The sequential anticoagulation therapy regimen of heparin injections in the first trimester and subsequent oral warfarin in the second and third trimesters has a lower risk of embryopathy. The regimen of UF heparin injections throughout pregnancy is devoid of embryopathy but has the highest risk of thromboembolic complications., LMW heparin has been reported to have the highest live birth rates compared to UF heparin and other forms of anticoagulation regimen.,
Some reports suggest the use of stratified PT/INR warfarin anticoagulation targets of 1.5–2.5, 2.0–3.0 and 2.5–3.5, depending on the location, types and number of mechanical valve prostheses. This could reduce the risk of embryopathy or foetal loss. Others also suggest that the addition of low-dose aspirin (75–100 mg daily) could improve outcomes in patients on low-dose warfarin of 5 mg or less, with lower PT/INR target. UF heparin could be used in place of LMW heparin in sequential regimen during the first trimester and also after 36 weeks of gestation, just before delivery., However, the patient has to be on admission in order to monitor the target APPTk of 1.5–2 times the level of control. LMW heparin is more convenient but expensive and can only be monitored with special antifactor Xa assay, which is not readily available in low income countries. Ideally, both the peak and trough levels of antifactor Xa should be monitored., Direct acting oral anticoagulants have not been found to be useful as alternative anticoagulation therapies in patients with mechanical valve prostheses. Jonathan et al., suggested the use of stented tissue valves in place of mechanical valve prostheses in women of childbearing age, in order to avoid the numerous challenges of poor drug compliance and inadequate anticoagulation monitoring amongst the indigent patients.
| Conclusion|| |
We have reported our experience with the daunting task of managing anticoagulation therapy in two pregnant women with mechanical valve prostheses, in a low socioeconomic setting. The first patient had three first trimester spontaneous abortions and subsequently had two successful pregnancies, despite being poorly compliant to her low-dose tablet warfarin therapy. The second patient was fairly compliant to subcutaneous LMW heparin therapy regimen with subsequent delivery of healthy twin boys by elective C/S. Inadequate anticoagulation therapy and monitoring remain a challenge in low-socioeconomic setting.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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