Anticoagulation for prosthetic heart valves during pregnancy: is

low-molecular-weight heparin an alternative?

Rainer G. Leyh, Stefan Fischer, Arjang Ruhparwar and Axel Haverich
Eur J Cardiothorac Surg 2002;21:577-579

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The European Journal of Cardio-thoracic Surgery is the official Journal of the European Association
for Cardio-thoracic Surgery and the European Society of Thoracic Surgeons. Copyright © 2002 by
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ISSN: 1010-7940.

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 European Journal of Cardio-thoracic Surgery 21 (2002) 577–579
www.elsevier.com/locate/ejcts
Case report

Anticoagulation for prosthetic heart valves during pregnancy:

is low-molecular-weight heparin an alternative?
Rainer G. Leyh*, Stefan Fischer, Arjang Ruhparwar, Axel Haverich
Division of Thoracic and Cardiovascular Surgery, Hanover Medical School, Carl Neuberg Strasse 1, 30623 Hannover, Germany
Received 25 May 2001; received in revised form 27 November 2001; accepted 12 December 2001

Abstract
We report on the treatment failure of low molecular weight heparin (LMWH) for anticoagulation in a pregnant woman that underwent
artificial mitral valve replacement 10 years prior to her pregnancy. Until she became pregnant warfarin was administered for anticoagulation,
but due to the often mentioned increased risk for warfarin-induced maternal and fetal complications, at gestational week 5 the anticoagulation
regimen was switched to subcutaneous application of low molecular weight heparin. At gestational week 24 our patient developed acute life-
threatening pulmonary edema and hemodynamic instability due to acute mitral valve thrombosis and underwent emergency valve re-
replacement with a biological porcine valve. She recovered uneventfully and gave birth to a healthy child at gestational week 35. In addition
to our case presentation we review the sparse evidence in the literature regarding anticoagulation in pregnant women with mechanical heart
valves and discuss the rational of different anticoagulation regimens with regards to maternal and fetal outcome. Special consideration is
directed towards LMWH administration as an alternative to oral anticoagulation during pregnancy in women with mechanical heart valves.
q 2002 Elsevier Science B.V. All rights reserved.
Keywords: Pregnancy; Anticoagulation; Prosthetic heart valves; Low molecular weight heparin

1. Introduction the rational of different anticoagulation regimens with

Patients with mechanical heart valves require lifelong
anticoagulation to reduce the risk of thromboembolic
events. Coumarin derivatives are the drugs of choice for
continuous oral anticoagulation. However, controversy
exists about the most efficient and safest anticoagulation
regimen in women with mechanical heart valves during
pregnancy [1–8]. Low molecular weight heparin (LMWH)
was considered to be a potential alternative to coumarin for
anticoagulation during pregnancy and it has been shown to
be safe and effective in pregnant women with a history of
deep vein thrombosis [9]. However, there is only little
evidence in the literature regarding the effect of LMWH
for long-term anticoagulation in pregnant women with
mechanical heart valves [10–16]. Here we report on a
case of a LMWH treatment failure resulting in life-threaten-
ing mechanical valve thrombosis in a pregnant woman who
received a mechanical mitral valve 6 years prior to her
pregnancy. Our patient was successfully treated by a biolo-
gical mitral valve re-replacement. In addition, we discuss
* Corresponding author. Tel.: 149-532-6581; fax: 149-532-5404.
E-mail address: leyh@thg.mh-hannover.de (R.G. Leyh).
1010-7940/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved.
PII: S 1010-794 0(01)01154-X
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regards to maternal and fetal outcome and with special
consideration to LMWH as an alternative strategy to oral
anticoagulation during pregnancy in women with mechan-
ical heart valves.
2. Case presentation
A 24 year-old woman with complex mitral valve pathol-
ogy received a mitral valve replacement with a 29 mm
Carbomedics mechanical bileaflet prosthetic valve (Sulzer
Carbomedics, Austin, TX) in 1994. In 2000 she became
pregnant. Oral anticoagulation with warfarin was stopped
at the 5th week of gestation in order to reduce the risk of
warfarin-induced embryopathy and LMWH (Reviparin,
3500 anti Xa U/thrice a day) was administered. Routine
echocardiography after discontinuation of warfarin revealed
normal heart function with no abnormal findings. A routine
standard ECG performed by her family doctor prior to preg-
nancy showed sinus rhythm. The woman was admitted to
our hospital at her 24th week of gestation with acute
pulmonary edema and hemodynamic instability. Echocar-
diography showed a severe thrombosis of the mitral valve
prosthesis. Emergency mitral valve re-replacement was
578 R.G. Leyh et al. / European Journal of Cardio-thoracic Surgery 21 (2002) 577–579

performed. During the operation the fetus was monitored by
cardiotocography by an obstetrician and tocolytic agents
were administered. Anesthesia was maintained with contin-
uous propofol and fentanyl infusions. A standard non-pulsa-
til extracorporal circulation set up was used. The prime
solution was composed of 1125 ml of Ringer’s lactate,
250 ml of albumin 5% and 125 ml of manitol 20%.
Normothermic cardiopulmonary bypass was initiated after
cannulation of the aorta and the superior and inferior vena
cava. Maternal blood pressure was set to be 80 mmHg and
the pump blood flow was $2.5 l/m 2 per min. When fetal
bradycardia developed the pump flow was increased. For
myocardial protection cold blood cardioplegia was infused
into the aortic root. The patient underwent mitral valve re-
replacement through a standard transseptal approach. A
large thrombus was found on the mitral valve prothesis
avoiding adequate function of both leaflets. After detailed
discussion with our patient regarding technical approaches
to and outcome following various kinds of valve replace-
ment strategies with special regards to the data published in
the literature, the patient decided her thrombosed mechan-
ical mitral valve to be replaced by a biological valve. The
post operative cause was uneventful and the patient was
disconnected form mechanical ventilation at the day of
operation. Normal fetal heart rates were observed on cardi-
otocographic examinations postoperatively. The woman
was discharged from hospital at the 23th postoperative
day and the pregnancy was carried out uneventfully.
3. Comment
Sufficient anticoagulation after mechanical heart valve
replacement is mandatory to prevent thromboembolic
complications. Pregnant women represent a special problem
due to the hypercoaguable state during pregnancy and the
lack of reliable data on safety and efficacy of different antic-
oagulation regimes during pregnancy. Three different antic-
oagulation regimens have been recommended in the
literature: (i) administration of coumadin derivatives
throughout pregnancy and subcutaneous unfractioned
heparins (UFH) near term; (ii) substitution of coumadin
derivatives with subcutaneous UFH in the first trimester
and near term; and (iii) subcutaneous UFH application
throughout pregnancy [1–8].
Each of the three ‘standard’ anticoagulative approaches
renders mother and fetus to different anticoagulation-related
complications. Chan and coworkers comprehensively
reviewed the literature from 1966 until 1997, which is the
most detailed overview on the evidence from reported cases
and patient cohorts regarding anticoagulation strategies in
pregnant women with mechanical heart valves [17]. These
data clearly demonstrate that the maternal risk of throm-
boembolic events and death is increased when coumadin
was replaced by UFH [17]. The majority of maternal deaths
was caused by thrombosis of the prosthetic valve [17]. Since
most of the maternal complications occurred when UFH’s
were used for anticoagulation, LMWH’s were considered to
be an alternative. Whereas the effectiveness of LMWHs as a
substitute of coumadin derivatives for the prevention of
thrombosis and pulmonary thromboembolism during preg-
nancy has been established [9], the role of LMWHs in
preventing valvular thrombosis or thromboembolic events
in patients with artificial heart valves has yet to be clarified.
The evidence in the literature regarding the long-term appli-
cation of LMWH as the only anticoagulant after mechanical
heart valve replacement is limited only to a few reports with
a total number of 24 patients and with catastrophic treatment
failure in 17% (four out of 24 patients) (Table 1) [10–16].
Underdosage of LMWH’s might account for some of the
treatment failures reported. However, there are no data
available in the literature regarding dose finding studies
for LMWH’s in the prevention of thromboembolic events
after mechanical heart valve replacement during pregnancy.
In summary, considering the limited evidence from the
literature and our own clinical observations, we believe that
a sufficient evidence-based anticoagulation therapy is
mandatory in order to reduce the maternal risk of throm-
boembolic complications following mechanical heart valve
replacement. Both coumadin derivatives and heparins
(LMWH and UFH) for anticoagulation carry hazards during
pregnancy, but whereas coumadin derivatives bring a small
risk to the fetus, heparins jeopardize the mother whose long-
term safety is paramount.

Table 1
Long-term anticoagulation with LMWH’s after mechanical heart valve replacement

First author Refs Year No. of patients Drug Dose Pregnancy Valve thrombosis Uneventful

Harenberg [13] 1997 n ¼ 16 Dalteparin 100 anti Xa U/kg per day – – n ¼ 16

Lee [12] 1996 n¼2 Nadroparin calcium 0.01 ml/kg twice a day n¼2 – n¼2
Idir [16] 1999 n¼1 Nadroparin calcium 0.6 ml once a day – n¼1 –
Maharay [15] 1999 n¼1 Dalteparin 16 000 anti Xa U/day – – n¼1
Abbilgaard [14] 1999 n¼1 Dalteparin – n¼1 – n¼1
Berndt [10] 2000 n¼1 Enoxaparin 20 mg once a day n¼1 n¼1 –
Lev-Ran [11] 2000 n¼2 Enoxaparin 40 mg twice a day n¼1 n¼2 –

Total n ¼ 24 n¼4 n¼4 n ¼ 20

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 R.G. Leyh et al. / European Journal of Cardio-thoracic Surgery 21 (2002) 577–579
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 Anticoagulation for prosthetic heart valves during pregnancy: is
low-molecular-weight heparin an alternative?
Rainer G. Leyh, Stefan Fischer, Arjang Ruhparwar and Axel Haverich
Eur J Cardiothorac Surg 2002;21:577-579
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